Non Small Cell Lung Cancer Treatment Results

March 4, 2015 by in category cancer research with 0 and 1

Non small cell lung cancer has a bleak prognosis and is one of the more aggressive forms of cancer. It is unfortunately also one of the most prevalent cancers. We present survival statistics, treatment patterns and most importantly clinical research and treatment efficacy measurements from documented and verified clinical trials.

The chart below shows the average mortality statistics (1 yr and 5 yr survival) of lung cancer patients, charted out by the stage of lung cancer when they were first diagnosed.

Relative Survival (%) by Lung Cancer Stage ( 1yr & 5 yr)

1 year and 5 year Lung cancer survival rate in UK

In general about 30% of patients whose lung cancer was first diagnosed at Stage 1 and 2 survive 5 years and more and there are reports of patients surviving and living cancer free after treatment much longer than that too. However, the survival rate does dip alarmingly for stage 3 and 4. Unfortunately about 70% of patients are diagnosed when their cancer is in the 3rd or 4th stage.

Non-Small Cell Lung Cancer Treatment Patterns by Stage

common treatment pattern employed for treating lung cancer

Surgical removal of tumors are a preferred treatment pattern in the initial stages of cancer. For stage 2 and 3, a combination of radiation therapy and chemotherapy is preferred as the cancer is no longer localized in such patients.

EGRF, ALK & KRAS Mutation Factor in Treating Lung Cancer

EGFR mutation has emerged as an important biomarker that is linked to improved treatment response amongst lung cancer patients . Recent studies 1 have proven that such patients show much improved response when treated with targeted therapies involving EGFR-TKI than with standard chemotherapy regimens. Various clinical analysis has shown that a survival time of close to 5 years is not uncommon even in in advanced lung cancer patients but with the EGFR mutations.

OncogenePrevalence of MutationPredicted Therapeutic ResponseResponse Rate Predicted
EGFRAsians: 40%
Caucasians: 10–15%
Most EGFR mutations are sensitive to EGFR TKIs - Vital for good treatment responseErlotinib: ~82%–83%
Gefitinib: ~71%–73%
ALK2–7%Could be
a) Sensitive to ALK inhibitors or
b) Resistant to EGFR TKIs
If sensitive to ALK inhibitors, response rate could be around 60%.
If resistant to EGFR TKIs, response rate is 0
KRASAsians: 10%
Caucasians: 30%
Resistant to EGFR TKIs0%–5% response rate

The above figure shows the aggregated treatment responses in patients with various mutations.Erlotinib and gefitinib are the recommended first line treatments for patients with EGFR mutations. These medications act as EGFR-TKI on the tumor that shows the EGFR mutation.

Quantified Summary of Results from Various Non Small Cell Lung Cancer Treatments

The following section details results from clinical trials of the various FDA approved treatments currently in practice. There are over 40 clinical trials documented here and each has been simplified so as to give even a layman a quick understanding of the key aspects like average overall survival, time to progression, stable disease time, treatment response parameters, adverse effects etc associated with the treatments when administered to hundreds of patients. All the data is validated with reliable sources.

Pl note: If you are the patient and would rather not read details of prognosis and current treatment efficacy, this is the time to stop reading. But there is a lot of good information here which could prove to be useful if your friend or family is suffering from the disease.

How effective is Pemetrexed in improving progression free survival in Advanced Non-Small Cell Lung Cancer patients who have previously undergone other treatments

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Eli, Lilly and Company conducted a clinical trial in 2009 to check the effectiveness of a drug – pemetrexed in patients with non-small cell lung cancer (NSCLC) who have previously been treated with chemotherapy.

A total of 216 patients suffering from advanced non-small cell lung cancer were enrolled in the study and were then divided into 2 groups. The patients had all already undergone prior anti-cancer therapy.

  • Group 1 received a lower dose of pemetrexed (500 mg/m2) while
  • Group 2 received a higher dose of the same (1000 mg/m2).

The patients were then evaluated on basis of their overall response to the treatment, duration for which they responded as well as Progression Free Survival of patients.

Pemetrexed nsclc treatment result

Patients of Group 1 responded better than Group 2 patients in terms of partial response to the treatment as well as stability of disease. Additionally, more number of group 2 patients showed progression of disease (increase in tumor size or appearance of new lesions) compared to group 1. Results have been graphically presented in Graph 1.

Pemetrexed-nsclc-clinical-trial2

In addition to assessment of the overall response of patients to the treatment, the duration of their response (how long they continued to respond to treatment) as well as Progression Free Survival i.e. how long their cancer remained stable without worsening was measured and the two groups were compared. As can be seen from Graph 2, in both cases, results of group 1 patients was better.

In order to assess the difference in the quality of life of patients undergoing these treatments, they were asked to score their ‘Quality of Life’ using a questionnaire with scores in it, once before starting the treatment and then after 3 months of treatment. Higher scores meant a better quality of life. When the responses of the patients of both the groups was compared, it was found that Group 1 (500 mg/m2) had higher scores i.e. their quality of life was better than Group 2 (1000 mg/m2).

The results of this trial thus suggest that pemetrexed enhances response rate and promotes disease stability. However, 500 mg/m2 dose seems to be the sweet spot and the higher dosage was not as well tolerated.

Effectiveness of using Erlonitib & Pemetrexed alone & in combination to treat Metastatic Nonsquamous NSCLC in non-smokers who are unresponsive to standard chemotherapy

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A clinical trial involving 240 Non-Small Cell Lung Cancer (NSCLC) patients who had never smoked was conducted by Eli Lily and Company in 2013 to check the effectiveness of combination of two drugs – Erlotinib and Pemetrexed versus either Pemetrexed alone and Erlotinib alone, in terms of progression-free survival (time until the objective worsening of the disease).

This trial had only patients who had locally advanced or metastatic Non-squamous Non-Small Cell Lung Cancer with a failed response to an initial chemotherapy treatment. Such resistant cancer cases are especially difficult to treat.

Non squamous lung cancer is the most common type of lung cancer and account for 40% of cases. It is also called Adenocarcinoma and is the type that starts in the outer regions of the lungs and spreads slower.

The participants of this trial were randomly divided into 3 groups:

  • Group 1 consisting of 78 participants were given Pemetrexed + Erlotinib
  • Group 2 consisting of 82 participants were given only Erlotinib
  • Group 3 consisting of 80 participants were given Pemetrexed

Effectiveness of Erlonitib and Pemetrexed in Lung Cancer patients

The above result looks a bit confusing. Clearly the combination therapy consisting of Pemetrexed and Erlotinib has decisively shown to induce the best progression free survival score in these advanced lung cancer patients when compared to the other 2 standalone groups. Infact the combination therapy has exhibited double the efficiency in terms of arresting the disease.

However it is edged out by the group only taking Erlotinib when it came down to overall survival. Its too close to call in terms of overall survival. So the advantage still seems to be with the combination therapy with its superlative ‘Progression Free survival’ score. More results depicted below will make this more decisive.

Survival after treatment with Erlonitib and Pemetrexed

Highest percentage of Group 1 patients gave response to the treatment given to them compared to Group 2 and Group 3. The results are encouraging with as much as 44.7% of patients showing partial or complete response to the combination therapy treatment.

Similar trend was seen when the percentage chance of the patient surviving atleast 12 months was interpolated for all three groups (ref: Graph 4). Again Pemetrexed in combination with Erlotinib seems to give the best result compared to the other 2 standalone therapies.

It appears that the combination of Pemetrexed and Erlotinib is effective in improving survival chances as well as enhancing the quality of life of non-smoker advanced lung cancer patients and is a better treatment approach than ‘only Pemetrexed’ and ‘only Erlotinib’.

How Elderly Patients Suffering from Advanced Non-small Cell Lung Cancer respond to treatment with a combination of Pemetrexed and Carboplatin

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Eli, Lily and Company conducted a clinical trial on 62 elderly patients(average age 76) suffering from advanced Non-small Cell Lung Cancer (NSCLC) in 2010 to study efficacy and safety profile of the combination of Pemetrexed and Carboplatin in treatment of advanced NSCLC in the elderly.

The participants of this trial received a combination of Pemetrexed + Carboplatin and thereafter their tumor response was measured to see the effect of this treatment. 28.6% of the participants gave either a complete response (total disappearance of tumor) or partial response (reduction in the size of tumor). This tumor response was measured till 18 weeks from start of the trial or first appearance of tumor reduction in patients.

Also, the average overall survival was measured for these patients which came out to be 10.4 months while 13.1% of them were expected to reach one year progression free survival.

Comparative Effectiveness of Docetaxel vs (PR104 with Docetaxel) in Treating Patients with relapsed Advanced Non-small Cell Lung Cancer

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A clinical trial undertaken by Proacta Incorporated in 2013 aimed to study the effectiveness of administering Docetaxel alone as compared to Docetaxel + PR104 in patients with advanced Non-small Cell Lung Cancer (NSCLC) – stage IIIb/IV. The patients in thus study included those whose cancer had relapsed after a period of improvement(by definition tougher to treat).

PR104 has given researchers the \’aha\’ moment. Pre-clinical study has determined that it can induce positive responses from advanced tumor lesions that are hypoxic or have a positive expression of AKR1C3.

Tumor hypoxia is associated with patients and its presence is attributed to increased resistance to standard chemotherapy and radiation treatments and the progression in such patients is very bleak. So this study was done to understand if PR104 therapy can help such patients.

After enrolling 38 NSCLC patients in the trial, they were randomly allocated to the 2 following groups:

  • Group 1 consisting of 17 patients who were given only Docetaxel
  • Group 2 consisting of 21 patients who were given Docetaxel + PR104

effectiveness of Docetaxel vs PR104 in treating lung cancer

After a period of 4 months, tumor response was measured in these two groups. 3 patients out of 17 from the second group who were given both the drugs gave responded to treatment while only 1 out of 21 responded to treatment with Docetaxel alone i.e. reduction in the lesions. PR104 seems to offer positives here for some patients but it is deemed that the result is not clinically significant overall. However considering that these patients were in the advanced stage and those whose cancer relapsed(more difficult cases). some doctors may deem this worth considering.

Adverse events when under Docetaxel and PR104 therapy

Additionally, when the participants were evaluated for the presence of adverse events (measured 30 days after the last drug dosage of the trial), Group 2 participants showed better results. Compared to Group 1 where 47% of the participants exhibited adverse health events, fewer (21.7%) Group 2 subjects had any adverse events (ref: Graph 6).

The combination of Docetaxel and PR104 is useful for some but probability of effectiveness is deemed clinically not significant by researchers. However it clearly produces lesser adverse effects than that from Docetaxel alone in patients with advanced relapsed and treatment resistant NSCLC.

How effective is the use of Erlotinib and Standard Chemotherapy in treatment of Advanced Non-small Cell Lung Cancer patients with poor performance status?

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A clinical trial was done in 2012 by Astellas Pharma Inc (OSI Pharmaceuticals ) on 103 advanced Non-small Cell Lung Cancer (NSCLC) patients with poor performance status, to assess the effectiveness of the drug erlotinib and standard chemotherapy in patients with advanced, previously untreated NSCLC.

All the participants (103) were randomly allocated to 2 groups:

  • Group 1 included 52 subjects who were treated with Erlotinib.
  • Group 2 included 51 subjects who were given standard chemotherapy treatment.

erlotinib bnsclc treatment results

On looking at the results of the study (Graph 7), it can be seen that the average overall survival as well as average progression free survival is higher in subjects who were given standard chemotherapy (carboplatin +paclitaxel) as compared to those who were treated with Erlotinib.

erlotinib nsclc treatment response

When the response to disease for both the treatment groups was observed (ref: Graph 8 and Graph 9), it was seen that higher percentage of Group 2 participants (standard chemotherapy) responded favorably to treatment i.e. higher percentage of this group showed partial response (reduction in tumor size and spread), stable disease (no further deterioration in disease) and fewer showed disease progression (further aggravation of tumor).

Standard chemotherapy (carboplatin +paclitaxel) treatment seems to be much more effective than treatment using Erlotinib in patients with advanced, previously untreated Non-small Cell Lung Cancer (NSCLC).

A Study of Effectiveness of (Alimta+Cisplatin+Gefitinib) vs only Gefitinib in Asian Non-smoking Participants with Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

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A clinical trial was carried out by Eli Lily and Company in 2014 on Asian locally advanced Non-small Cell Lung Cancer (NSCLC) patients who never smoked, to see the comparative effect of using a combination of three drugs: Alimta+Cisplatin+Gefitinib vs only Gefitinib in treatment of these patients.

236 non-smoking, Asian NSCLC patients were enrolled in this study and were randomly assigned to one of the two groups:

Group 1 (118 participants) – prescribed combination of the 3 drugs: Alimta+Cisplatin+Gefitinib
Group 2 (118 participants) – prescribed only Gefitinib

progression free survival with Alimta Cisplatin Gefitinib

Graph 10 represents the average duration of progression free survival among the participants across treatment groups. It is apparent that Group 2 which was given only Gefitinib fared better than Group1 which was given a combination of Alimta, Cisplatin and Geftinib in terms of higher progression free survival.

treatment response with Alimta Cisplatin Gefitinib

In case of treatment response given by both treatment groups, as can be seen from Graph 11, Group 2 fared better when it came to giving complete/partial response i.e. complete disappearance or reduction in tumor lesions respectively. However, more percentage of Groups 1 participants showed stability of disease as compared to their counterparts in Group 2.

While the average duration of progression free survival among these non-smoking, Asian NSCLC patients was lower in Group 2 (only Gefitinib), higher percentage of participants responded completely or partially and showed disease stability. Hence, although not decisively conclusive, the research seems to suggest that using the combination of the 3 drugs seems to have beneficial effect on more patients which suggests its higher suitability for use in treatment.

How effective is Methotraxate in treating Inoperable Lung Cancer Patients?

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In 1977, Selawry and co-researchers conducted a clinical trial on lung cancer patients to check the effectiveness of the drug Methotraxate in them. Lung cancer patients were enrolled and divided into 3 treatment groups:

  • Group 1 (48 patients) who were given high dose methotraxate
  • Group 2 (37 patients) who were given lower dose of methotraxate
  • Group 3 (32 patients) were given Placebo (drug similar to methotraxate in appearance but not containing any medication. So, the patients were under impression that they were receiving methotraxate but were actually not given the drug).

After this, objective tumor response (at least 50% reduction in tumor) of the patients in all 3 groups was measured. All the treatments were well-tolerated by patients and did not cause any life threatening toxicity.

response to nsclc with methotraxate

As seen in Graph 12, highest improvement was shown by Group 1 which was given higher dose of methotraxate followed by Group 2 (lower dose methotraxate) and placebo (no methotraxate).

methotraxate treatment results with epidermoid carcinoma

Similar trend was seen when the patients’ response to epidermoid carcinoma (squamous cell carcinoma) was measured. Highest response was given by Group 1 patients followed by Group 2 while predictably, the placebo group showed no positive effect. This part of the trial included 23 patients in Group 1, 11 patients in Group 2 and 13 patients in Group 3.

It can thus be concluded that methotrexate at “high dose (0.06 mg/kg/dose)” is a potentially useful drug for improving the prognosis in patients suffering from epidermoid carcinoma of the lung. Its also interesting to note that Leukopenic (those with decreased white blood cell count) patients lived longer than others irrespective of the objective response rate.

Clinical Trial to Assess Effectiveness of Ceritinib in Patients with Advanced ALK-rearranged Non-Small Cell Lung Cancer

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A clinical study conducted was by Shaw and his co-researchers and funded by Novartis Pharmaceuticals, in 2014 to evaluate effectiveness of the drug Ceritinib in treating patients with advanced ALK-rearranged Non-Small Cell Lung Cancer (NSCLC). Initially, acceptable and best dose of ceritinib was identified for using as treatment dose.

After this, 103 patients who had advanced ALK-rearranged NSCLC were enrolled in the study and administered upto 400 mg/day Ceritinib. Out of these, 80 patients were such who had been previously treated using Crizotinib (another drug with similar action).
Treatment response by ALK rearranged lung cancer patients with Ceritinib
More than half of the patients enrolled in the study gave positive response to treatment with the treatment response of the first group (previously untreated group) being slightly higher than that of the second group (previously treated with Crizotinib).

Average progression free survival for these patients was 7 months.

Ceritinib was highly active in patients with advanced, ALK-rearranged NSCLC, including those who had previously been treated with and had disease progression during crizotinib treatment.

A Study Comparing Two Different Treatment Regimens in Patients with Stage IIIB or IV Non-Squamous Non-Small Cell Lung Cancer

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Eli Lilly and Company conducted a clinical trial in 2014 to compare the beneficial effect of using a combination of Pemetrexed + Carboplatin + Bevacizumab versus Paclitaxel + Carboplatin + Bevacizumab on the treatment response and survival in Non-small Cell Lung Cancer (NSCLC) patients.

A total of 939 patients were enrolled in the study and were randomly divided into two treatment groups:
1. Group 1 had 472 participants who were treated using a combination of Pemetrexed + Carboplatin + Bevacizumab
2. Group 2 had 467 participants who were treated using a combination of Paclitaxel + Carboplatin + Bevacizumab
Pemetrexed, Carboplatin and Bevacizumab in treating non small cell lung cancer
As depicted in Graph 16, Groups 2 participants showed better disease control (disappearance/reduction in tumor lesions or stability of disease) than Group 1.
Overall survival of NSCLC patients under treatment involving Pemetrexed,Carboplatin and Bevacizumab

Progression Free Survival (PFS)
Out of all the patients in Group 1, 50% lived progression free for a minimum of 6.04 months. Data suggests that some patients of this group lived progression free for as long as 6.9 months while the shortest PFS was 5.5 months.

In case of Group 2, the median duration of PFS was 5.5 months which is a little lower than Group 1.The estimations for highest and lowest duration of PFS were 5.9 months and 5.4 months. These were also relatively lower compared to Group 1.

Overall Survival (OS)
The median duration of OS for Group 1 was 12.5 months while it was higher in Group 2 (13.4 months). The lowest and highest duration of OS estimated for Group 1 were 11.3 months and 14 months respectively which were similar to those in Group 2; 11.9 months and 14.9 months.

Though Group 1 patients showed marginally higher progression free survival, Group 2 showed better disease control and patients of this group survived longer than Group 1. On the basis of this evidence, we can conclude that treatment combination of Paclitaxel + Carboplatin + Bevacizumab (Group 2) seems more effective than Pemetrexed + Carboplatin + Bevacizumab (Group 1) in improving treatment response in NSCLC patients.

Effectiveness of Gemcitabine alone Vs Gemcitabine with Docetaxel after treatment with Cisplatin, Etoposide and Radiation in Stage III Unresectable NSCLC Patients

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Eli Lily and Company conducted a clinical trial in 2010 to compare effectiveness of the drug Gemcitabine when used alone and in combination with Docetaxel in treating Non-Small Cell Lung Cancer (NSCLC) patients who have been already treated with Cisplatin, Etoposide and Radiation.

Out of the 64 participants who were enrolled in the study, half (32) were randomly allocated to Group 1 which was given only Gemcitabine and the other half (32) were allocated to Group 2 which was given Gemcitabine + Docetaxel.

Gemcitabine with Docetaxel after Treatment with Cisplatin

Higher percentage of patients who were on Gemcitabine and Docetaxel were alive after 2 years of treatment initiation and also gave better treatment response (disappearance or reduction in tumor lesions) than the patients who were only on Gemcitabine.

Gemcitabine with Docetaxel

Progression Free Survival (PFS): The median value is that value which divides the patients into 2 equal groups. 50% of the patients fall below this value and other 50% are above this value. The median duration of PFS of Group 1 (162.5 days) was lower compared to Group 2 (408 days). This shows that 50% of the patients of Group 1 lived for at least 162 days while in Group 2, 50% of patients lived for 408 days or more.

Also, the lowest and highest duration of PFS was estimated for both groups. For Group 1 lowest and highest duration of PFS was 82 days and 239 days. For Group 2, these values were higher; 141 days and 708 days.

Overall Survival (OS): Median duration of OS was 492.5 days for Group 1 and much higher (899 days) for Group 2. Lowest and highest duration of OS also followed similar pattern. Lowest OS in Group 1 was 299 days while in Group 2 it was 498 days. Highest duration of OS in Group 1 was 1034 days and Group 2 it was 1583 days.

Thus, across all the measured parameters, the combination of Gemcitabine and Docetaxel seemed much more effective compared to Gemcitabine alone in improving longevity and treatment response in these Stage 3 unresectable NSCLC patients.

Exploring the Clinical Benefits of Using Crizotinib in locally advanced or metastatic ALK-Positive NSCLC Patients

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Bryant conducted a clinical trial in 2013 to review the characteristics and clinical benefits of using the drug Crizotinib for treatment of patients suffering from ALK-positive Non-Small Cell Lung Cancer (NSCLC).

Use of Crizotinib showed improved response rates (50-57%) and also extended the duration of response (6-10 months). These results were instrumental in getting FDA (Food and Drug Administration) for Crizotinib for pharmaceutical use.

Crizotinib is a novel targeted anticancer agent that appears to be a favorable treatment option for patients with locally advanced or metastatic NSCLC that is ALK-positive as detected by an FDA-approved test.

How effective is Affatinib in treating EGFR FISH +ve, Advanced(Stage IIIB or IV) NSCLC

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Boehringer Ingelheim conducted a clinical trial in 2013 on 69 advanced non small cell lung cancer patients to check the effectiveness of the drug Afatinib, as measured by objective response (i.e. disappearance reduction in tumor lesions), progression free survival as well as overall survival of the patients

Affatinib treatment response

As can be seen from Graph above, considerable proportion of patients showed complete/partial response to treatment (i.e. disappearance or reduction in the tumor lesions), as well as stability of disease (no worsening or aggravation of tumor). Put together, more than half of the enrolled patients exhibited control over their disease on treatment i.e. stability or regression in tumor.

Lung cancer survival with Affatinib

Progression Free Survival (PFS): Since the median PFS was 8.4 weeks, it means that half of these patients lived without any increase in disease for at least 8.4 weeks. Some patients lived progression free for as long as 15.7 weeks while some could remain progression free for 7.4 weeks.

Overall Survival (OS): The median duration for OS among the patients was 50.4 weeks. The lowest OS duration was estimated to be 33.5 weeks and highest was 64 weeks.

Afatinib seems effective in improving the treatment response among patients having advance non small cell lung cancer.

Is Crizotinib more effective than Chemotherapy in Advanced ALK-positive Lung Cancer?

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In a study conducted by Pfizer in 2013, Shaw and his co-researchers compared the effectiveness of the drug Crizotinib versus Chemotherapy (using Paclitaxel or Docetaxel) in patients suffering from ALK-positive Non-Small Cell Lung Cancer (NSCLC), all of whom received atleast one previous platinum-based regimen.

347 patients were randomly allocated to the two different treatment groups and their treatment response as well as progression free survival was observed.

Crizotinib vs chemotherapy

 

Graph above clearly shows that Group 1 patients who were given Crizotinib had a much higher median duration of progression free survival compared to Group 2 i.e. the chemotherapy group.

Crizotinib vs chemotherapy

Group 2 patients also responded better to the treatment in terms of disappearance/reduction in tumor lesions and stability of disease (ref: Graph above).

Results also said that patients reported greater reductions in symptoms of lung cancer and greater improvement in global quality of life with Crizotinib than with chemotherapy.

Crizotinib is superior to standard chemotherapy in patients with ALK-positive advanced Non-Small Cell Lung Cancer.

Clinical Trial assessing the benefit of using Ipilimumab with Paclitaxel/Carboplatin in treating patients with previously untreated Advanced NSCLC or Extensive Stage SCLC

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A clinical trial conducted in 2012 across including participants from United States, France, Germany, India, Italy, Poland, Russian Federation, Ukraine was sponsored and conducted by Bristol-Myers Squibb to assess the safety and efficacy of the drug ipilimumab in patients suffering from advanced lung cancer (NSCLC and SCLC) and to determine whether ipilimumab given with paclitaxel/carboplatin has clinical benefit when compared with paclitaxel/carboplatin alone in patients with previously untreated lung cancer.

The study was done on 331 lung cancer patients (both male and female) who were randomly allocated to one of the following 2 treatment groups:

  • Group 1 consisted of 222 subjects who were given drug intervention (Ipilimumab/ placebo + paclitaxel + carboplatin).
  • Group 2 consisted of 109 subjects who were given placebo intervention i.e. the patients were being given a drug which had no anticancerous effect but they were unaware of this (Ipilimumab placebo + paclitaxel + carboplatin).

It was a double blind study i.e. neither the participant nor the investigator were aware which group was receiving which intervention i.e. whether real drug (ipilimumba) was being given or placebo was being given. This is done in this type of studies to avoid any kind of bias on part of either participant or investigator and thus ensure accurate study results.

Ipilimumab-lung-cancer-treatment-1

Among patients suffering from Nonsmall Cell Lung Cancer, the results show that the average Progression Free Survival as well as Overall Survival was higher in the group that received the drug ipilimumab i.e. Group 1 compared to Group 2 subjects who didn’t receive it (Graph above).

Lung cancer treatment results with Ipilimumab

However, as can be seen from data depicted in Graph above, in the case of subjects suffering from Small Cell Lung Cancer, there was no appreciable difference in the Progression Free Survival as well as Overall Survival of the two groups of patients.

This clinical trial suggests that usage of Ipilimumab along with Paclitaxel and Carboplatin improves overall survival and progression free survival in NSCLC but the same seems to offer no noticeable improvement in SCLC patients.

Is Low Dose Helical Computed Tomography(LDCT) scan more effective than Chest Radiography(CXR) in screening individuals who are at high risk of developing Lung Cancer?

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A clinical trial was conducted in 2014 by the National Cancer Institute and the American College of Radiology Imaging Network to compare the effectiveness of two types of diagnostic methods (LDCT scan – Low Dose Helical Computed Tomography and CXR – Chest Radiography) in screening individuals who are at high risk for developing lung cancer.

This study was conducted with an aim to help doctors detect cancer early and plan curative treatment at the earliest and save valuable time and facilitating better treatment outcome for patients with lung cancer.

A total of 53,454 consenting participants were enrolled across the United States. The participants were followed up for 6.5 years since the initiation of the study.

LDCT vs CXR screening

LDCT screening was able to diagnose higher number of cases of lung cancer compared to CXR. Also, death due to lung cancer was lower in the LDCT group compared to CXR group which can be a reflection of the better diagnostic ability of LDCT compared to CXR.

LDCT scan seems to be better at diagnosis and thus helps in improving prognosis in lung cancer patients with early detection.

Clinical Trial to check efficacy of Palifermin in reducing in unresectable stage III NSCLC

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A clinical trial was conducted by Swedish Orphan Biovitrum in collaboration with Amgen to determine in 2014 if the use of the drug palifermin is helpful in reducing dysphagia (difficulty in swallowing) in patients suffering from Non-small Cell Lung Cancer (NSCLC) and undergoing chemotherapy.

The trial was conducted on 95 lung cancer patients who were divided into two groups:

  • Group 1 participants (49) received chemotherapy, radiotherapy as well as the drug palifermin.
  • Group 2 participants (46) received chemotherapy and placebo radiation therapy (i.e. the subjects were not receiving actual radiation but thought they were getting it).

Palifermin for dysphagia

Palifermin for dysphagia

The trial concluded that the group of subjects who were given palifermin had lower prevalence as well as duration of dysphagia compared to the placebo group (ref: Graphs above) who did not receive palifermin.

This suggests that use of Palifermin in lung cancer patients may help in reducing the severity and duration of dysphagia among them which would in turn improve their food intake and lead to better quality of life.

Does Romiplostim reduce Chemotherapy Induced Thrombocytopenia in NSCLC patients

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In a clinical trial carried out in 2013 by Amgen, 62 lung cancer patients were enrolled to study the effect and possible benefit of the drug Romiplostim for the treatment of chemotherapy induced thrombocytopenia.

Thrombocytopenia is the reduction in the number of blood fragments known as platelets in the body resulting in fatigue, general weakness and further health complications if left untreated. It is a symptom seen in patients with receiving gemcitabine and platinum for NSCLC.

All the patients who were participating in the study were divided into 4 groups as follows:

  • Group 1 – Chemotherapy + a placebo injection (i.e. they thought that they were receiving the drug Romiplostim but they were actually not being given the same).
  • Group 2 – Chemotherapy + 250 µg of the drug Romiplostim
  • Group 3 – Chemotherapy + 500 µg of the drug Romiplostim.
  • Group 4 – Chemotherapy + 750 µg of the drug Romiplostim.

It was a double blind study i.e. neither the participant nor the investigator were aware which group was receiving which intervention i.e. whether real drug (Romiplostim) was being given or placebo was being given. This is done in this type of studies to avoid any kind of bias on part of either participant or investigator and thus ensure accurate study results.

The patients were then evaluated for occurrence of adverse events, occurrence and duration of thrombocytopenia.

Romiplostim treatment result for CIT

Romiplostim-cit-2

Looking at the results shown in Graph above, it can be said that while group 4 experienced least adverse effects, even less than the group that was not given the drug (placebo group), when it came to occurrence and duration of thrombocytopenia, group 3 patients were better than all 3 groups.

Also, there was very little difference between the placebo group and the groups given varying doses of Romiplostin with regards to adverse events as well as thrombocytopenia. In fact, the placebo group showed lesser duration of thrombocytopenia as compared to group 3.

Hence, it cannot be said with confidence that Romiplostin has a beneficial effect on chemotherapy induced thrombocytopenia in patients suffering from lung cancer.

Can Zoledronic Acid(Reclast) delay Bone Metastases in Stage 3 NSCLC patients?

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It is seen that 30-40% of patients with lung cancer develop bone metastases during the course of their disease, which can lead to pain, decreased mobility and skeletal complications.

Novartis Pharmaceuticals did a study in 2011 to investigate the effect of Zoledronic acid on preventing or delaying the development of bone metastases and its impact on disease progression/survival in patients with stage 3 NSCLC.

A total of 447 patients suffering from stage 3 NSCLC participated in the study and were randomly divided into2 groups as follows:

  • Group 1 included 226 subjects who were given the drug Zoledronic acid
  • Group 2 included 221 participants who was not given Zoledronic acid.

The results of this trial indicated that the average duration of Progression Free Survival was higher in the control group (11.3 months) compared to the group which was being given the drug Zoledronic acid (9 months).

Zoledronic acid for bone metasteses

Data was also collected from subjects after 6 months, then again after 12 months, then 18 months and then 24 months to see how many of the patients in each group had developed bone metastasis.

At each evaluation (i.e. 6, 12, 18 and 24 months), lower percentage of Group 1 participants had developed bone metastases compared to Group 2.

This suggests that giving Zoledronic acid to stage 3 Non-small Cell Lung Cancer patients may prolong better quality of life.

Testing the effectiveness of Whole Brain Radiation Therapy (WRT) and Stereotactic Radiosurgery when used alone or in combination with Temozolomide or Erlonitib in prolonging survival among Non-Small Cell Lung Cancer patients with Brain Metastases

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In 2014, the National Cancer Institute conducted a clinical trial on 126 non-small cell lung cancer patients with brain metastases to see if whole-brain radiation therapy and stereotactic radiosurgery were more effective when used alone or in combination with the drug Temozolomide or Erlotinib.

The subjects were randomly allocated to three groups as follows:

  • Group 1 included 45 patients who were given – whole-brain radiation therapy and stereotactic radiosurgery.
  • Group 2 included 40 patients who were given – whole-brain radiation therapy and stereotactic radiosurgery + Temozolomide
  • Group 3 included 41 patients who were given – whole-brain radiation therapy and stereotactic radiosurgery + Erlotinib

Whole Brain Radiation Therapy results

The median duration of overall survival among the patients in Group 1 was 13.4 months. This can be interpreted as: 50% of the patients in group 1 lived for a minimum period of 13.4 months. The shortest duration for which the patients of this group lived was 6.5 months while some survived up to 20.8 months also.

The median duration of OS for Group 2 (6.3 months) and Group 3 (6.1 months) were almost similar and both were much lower than Group 1. The shortest and longest duration of OS among patients in these two groups were also much less than Group 1. In Group 2, shortest OS was 3.4 months and longest was 10.1 months.

In Group 3, these values were 3.6 months and 12.2 months respectively.

Looking at these results, it appears that treating NSCLC patients with radiation therapy and stereotactic radiosurgery alone is better than combining this treatment with either Erlotinib or Temozolomide.

Clinical Study of Vandetanib combined with Chemotherapy to treat Advanced NSCLC

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Previous research studies conducted on lung cancer treatment have shown that the ability to treat lung cancer could be significantly improved by not only targeting the tumor cells directly with chemotherapy, but also by cutting off the blood supply to the cancer cells. Vandetanib is an investigational drug that acts by restricting this blood supply and thus could be effective in slowing the tumor progression.

Keeping this in mind, PrECOG, LLL conducted a clinical trial in 2012 to determine if the addition of Vandetanib to a standard chemotherapy regimen will slow or stop the growth of the cancer for a longer period of time compared to the time period generally gained from the use of standard chemotherapy alone.

For this clinical trial, 162 patients suffering from NSCLC (Non-small Cell Lung Cancer) were selected and randomly divided into 2 groups as follows:

  • Group 1 had 82 patients who were given chemotherapy + Vandetanib
  • Group 2 had 80 patients who were given chemotherapy + Placebo (i.e. patients thought they were being given the investigational drug Vandetanib but were not actually being given Vandetanib).

It was a double blind study i.e. neither the participants (patients) nor the people conducted the trial were aware which group was being the drug Vandetanib and which group was being given placebo.

Vandetanib for non small cell lung cancer

 

Vandetanib for lung cancer

The group which was given the investigational drug (Vandetanib) in addition to chemotherapy had a higher median duration of PFS (4.5 months) compared to the other group (4.2 months). This can be simplified to say that in the first group, 50% of the patients lived without disease aggravation for at least 4.5 months while in Group 2, this duration was shorter (4.2 months).

The researchers also estimated what was the shortest PFS and longest PFS in both groups. For Group 1, shortest PFS was 3.3 months and longest was 5.8 months while these values were lower in the placebo groups (2.8 months and 4.9 months respectively). Thus, progression free survival was better in the Group 1 patients.

Similarly, when the overall response rate of the patients was seen, it was found that higher percentage of Group 1 patients had responded (in terms of reduction in tumor) compared to Group 2 (18.8% vs 18.3%).

Administering a combination of chemotherapy and Vandetanib gave marginally better treatment response in this clinical trial compared to chemotherapy alone in patients suffering from NSCLC.

Can the new Anticancer Drug – BAY 43-9006 (Sorafenib) improve treatment response in Advanced Progressive Relapsed Refractory NSCLC ?

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With an aim of improving the prognosis of patients with advanced, relapsed, progressive and refractory non-small cell lung cancer (NSCLC), which is extremely difficult to treat, the National Cancer Institute conducted a clinical trial in 2012 on such patients using the a new anticancer drug – BAY 43-9006 (Sorafenib).
NSCLC treatment with Sorafenib
BAY 43-9006 is known to inhibit Raf and is also known to inhibit other kinases including VEGFR2, VEGFR3, PDGFR-beta, Flt3, c-KIT and p38(1). It has also shown in-vitro activity against NSCLC cell lines – NCI-H460 and A549 with inhibition of tumor growth by 27% to 68%.

Researchers were especially interested to see if the BAY 43-9006 ‘s Raf inhibition could have potential anti-cancer effects since mutations in the Raf pathway is known to accelerate the cancer and such patients have poorer mortality rates.

A total of 34 patients were enrolled in this study and were asked to take the drug after which their response rate, progression free survival, overall survival was observed at the end of 17 months from the date of enrollment.

The following highlights emerged:

  • 6% of the participants responded completely/partially to the treatment i.e. reduction or complete disappearance of target lesions.
  • The median duration of progression free survival for these participants was 3.4 months. This means that half of the patients lived for more than 3.4 months and the other half lived less than 3.4 months.
  • Median overall survival duration was 11.6 months. So, half of the patients survived for more than 11.6 months while 50% died before 11.6 months.

Clinical Trial to compare the effect of (Paclitaxel and Carboplatin) used alone and in combination with the drug Vorinostat in Stage IIIB or IV NSCLC patients

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Merck Sharp & Dohme Corp. conducted a clinical trial in 2013 to compare the treatment response, progression free survival as well as overall survival among patients suffering from Non-Small Cell Lung Cancer (NSCLC) when given Paclitaxel and Carboplatin with and without Vorinostat (investigational drug).

For this, 253 NSCLC patients were enrolled and randomly divided into the two following treatment groups:

  • Group 1 had 126 participants who were given Vorinostat + Paclitaxel + Carboplatin
  • Group 2 had 127 participants who were given Placebo + Paclitaxel + Carboplatin

It was a double blind study i.e. neither the participant nor the investigator were aware which group was receiving which intervention i.e. whether real drug (Vorinostat) being given or placebo was being given.

Vorinostat-nsclc-1

 

Vorinostat-nsclc-2

 

Progression Free Survival (PFS): Graph 1 shows that the median duration of PFS was 4.3 months for Group 1 which means that half of the patients in Group 1 lived without disease progression for 4.3 months or more. The maximum duration of PFS for this group was 13.4 months while minimum duration was 0.03 months.

For Group 2, the median duration of PFS was higher (5.5 months) than Group 1 but the lowest and highest values for PFS for Group 2 were 0.03 months and 13.8 months which are similar to Group 1.

Overall Survival (OS): In Group 1, half of the patients lived (with or without disease progression) for at least 11 months. The shortest time for which a patient of this group survived was 0.2 months but some patients also lived as long as 17.3 months.

Compared to this, Group 2 patients showed relatively better survival statistics with a higher median duration of 14 months. Patients of this group had a lowest PFS of 0.03 months and highest 18.7 months.

Group 2 showed better disease response that Group 1 (ref: Graph 2). The severity of the disease reduced in more patients of the placebo group.

On all counts such as reduction in disease severity, overall survival and progression free survival placebo group was superior. In this trial the results suggest that it is better to use Paclitaxel and Carboplatin alone, rather than using it with Vorinostat for treatment of NSCLC patients.

Use of Radiofrequency Ablation and External-Beam Radiation Therapy in treating patients with Stage I Non-Small Cell Lung Cancer that cannot be removed by Surgery

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Radiofrequency ablation uses a high-frequency electric current to kill tumor cells. External-beam radiation therapy uses high-energy x-rays to kill tumor cells. Giving radio frequency ablation together with radiation therapy may kill more tumor cells.

In 2014, Comprehensive Cancer Center of Wake Forest University collaborated with the National Cancer Institute to conduct a clinical research study for assessing the usability of radio frequency ablation and external-beam radiation therapy in treatment of patients with medically inoperable stage 1 Non-small Cell Lung Cancer (NSCLC).

This treatment was given to 13 inoperable, stage 1 NSCLC patients and progression free survival (patient is living with no increase or spread in cancer) was measured after 2 years from the date of initiation of the study.

It was found that at the end of 2 years, 61% of the patients were surviving, without further aggravation in their disease i.e. showed progression free survival.

This result is encouraging and suggests that use of radiofrequency ablation coupled with external beam radiation therapy in such patients could go a long way in improving their longevity without worsening of cancer.

Is Proton Beam Radiotherapy Combined with Chemotherapy effective in treating Locally Advanced Unresectable NSCLC ?

25


Loma Linda University conducted a clinical trial in order to determine the effectiveness of proton beam radiotherapy combined with chemotherapy for treatment of locally advanced Stage 3A and 3B Unresectable NSCLC. These cases are deemed difficult to treat.

The combination treatment (proton beam radiotherapy + chemotherapy) was given to 28 NSCLC patients who were enrolled in the clinical trial. Thereafter, the median duration of Overall Survival was 15 months. The scientists estimated from the collected data that highest duration for which a participant of this group survived was 20 months and lowest was 10 months.

Safety of this treatment was also evaluated by observing how many participants experienced treatment toxicity (Grade 3 or higher esophageal toxicity). About 7% of the enrolled participants showed signs of treatment toxicity.

This treatment seems to be effective in enhancing survival time of patients suffering from Advances Unresectable NSCLC.

Is Fentanyl Sublingual Spray an effective analgesic for relief from cancer pain?

26


INSYS Therapeutics Inc and National Cancer Institute did a clinical trial in 2014, involving 184 patients suffering from Non-small Cell Lung Cancer to study the clinical response to Fentanyl Sublingual Spray as a treatment for cancer pain.

The study medication Fentanyl Sublingual Spray is administered under the tongue as a simple spray and can be self-administered by patients or assisted by their caregivers.

A maximum, tolerable dose of the fentanyl sublingual spray was identified for these patients i.e. a dose which gave maximum pain relief without unacceptable side effects. Thereafter, the subjects were randomly allocated to two groups, each containing 92 patients.

While Group 1 was given the study medication (Fentanyl Sublingual Spray) 7 times, Group 2 received a placebo (participants think they are receiving the drug while they are actually not getting it) 3 times.

The drug was given when the patient experienced pain and the effect of the drug was measured by ranking intensity of pain felt by patient after 5, 10, 15, 30, 45 and 60 minutes of drug dosage.

This pain intensity was measured using the Summed Pain Intensity Difference score. A higher score indicates less pain. Participants were also asked to assess the Total Pain Relief felt by them after medication. A higher score indicates more pain relief.

Fentanyl Sublingual Spray to alleviate cancer pain

Graph 1 data clearly indicates that at every given time (5,10, 15, 30, 45 and 60 min) after administration of medication, the group that was given Fentanyl sublingual spray scored higher i.e. had lower intensity of pain compared to the placebo group. Also, the difference in SPID scores increased with increase in time which means that as time passed, pain intensity among group 1 participants kept decreasing.

Fentanyl Sublingual Spray for cancer pain relief

Similar to results of SPID scores, TOTPAR scores also showed that the first group (which was given fentanyl sublingual spray) fared better i.e. scored consistently higher than the placebo group through 60 minutes after dose administration.

It can thus be concluded from the results of this trial that use of Fentanyl Sublingual spray in patients with NSCLC would go a long way in providing pain relief and thus contribute to their quality of life.

Study of Pazopanib and Pemetrexed in Nonsquamous Cell Stage IIIB and IV NSCLC

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In 2013, GlaxoSmithKline conducted a clinical trial to check the effectiveness of treating non small cell lung cancer patients with pazopanib + pemetrexed compared to cisplatin + pemetrexed.

92 patients participated in the trial. They were then randomly divided into 2 groups.

  • Group 1 had 65 participants who were given pazopanib + pemetrexed.
  • Group 2 had 35 participants who were given cisplatin + pemetrexed.

Pazopanib-Pemetrexed-nsclc-treatment-1

Graph 1 indicated better progression free survival among patients of Group 1. The median duration of PFS among Group 1 was 25 months which means half of them lived for at least 25 months with no further growth in their cancer.

While some patients of this group lived progression free for 17.3 months, some were able to live up to 34.1 months without any signs of further cancer growth.

In case of Group 2, the median duration of PFS was lower (22.9 months). The lowest and highest duration of PFS among these patients was 18.4 months and 27 .7 months.

Pazopanib-Pemetrexed-nsclc-treatment-2

The graph shows that more patients of Group 2 gave partial & complete response, or had stability of disease compared to Group 1. But it is important to note here that treatment response of a large majority of the Group 1 patients and some of Group 2 patients was “unknown”. Therefore, we cannot conclude that Group 2 gave better treatment response.

Based on available data in this trial, (Pazopanib + Pemetrexed) seems to be a good treatment option and could be an alternative option to (Cisplatin + Pememtrexed) for some patients.

References:

  1. Mok T, Wu YL, Thongprasert S, et al. Phase III, randomized, open-label, first-line study of gefitinib (G) vs carboplatin/paclitaxel (C/P) in clinically selected patients (pts) with advanced non-small cell lung cancer (NSCLC) (IPASS) Stockholm, Sweden: 2008.
  2. ClinicalTrials.gov Trial Identifier: NCT00191191; Last verified: December 2009; Sponsor: Eli Lilly and Company
  3. ClinicalTrials.gov Trial Identifier: NCT00550173; Last verified: January 2013; Sponsor: Eli Lilly and Company
  4. ClinicalTrials.gov Trial Identifier: NCT00350792; Last verified: October 2010; Sponsor: Eli Lilly and Company
  5. ClinicalTrials.gov Trial identifier: NCT00862134; Last verified: January 2013; Sponsor: Proacta, Incorporated
  6. ClinicalTrials.gov Trial Identifier: NCT00085839; Last verified: August 2012; Sponsor: OSI Pharmaceuticals
  7. ClinicalTrials.gov Trial Identifier: NCT01017874; Last verified: February 2014; Sponsor: Eli Lilly and Company
  8. ncbi.nlm.nih.gov/pubmed/880567
  9. ncbi.nlm.nih.gov/pubmed/24670165
  10. ClinicalTrials.gov Trial Identifier NCT00762034; Last verified: August 2014; Sponsor: Eli Lilly and Company
  11. ClinicalTrials.gov Trial Identifier NCT00191139; Last verified: February 2010; Sponsor: Eli Lilly and Company
  12. ncbi.nlm.nih.gov/pubmed/23386065
  13. ClinicalTrials.gov Trial Identifier NCT00796549; Last verified: July 2014; Sponsor: Boehringer Ingelheim
  14. ncbi.nlm.nih.gov/pubmed/23724913
  15. ClinicalTrials.gov Trial Identifier NCT00527735; Last verified: June 2012; Sponsor: Bristol-Myers Squibb
  16. ClinicalTrials.gov Trial Identifier NCT00047385; Last verified: October 2012; Sponsor: National Cancer Institute (NCI)
  17. ClinicalTrials.gov Trial Identifier NCT00094861; Last verified: January 2014 ; Sponsor: Swedish Orphan Biovitrum
  18. ClinicalTrials.gov Trial Identifier NCT00413283; Last verified: September 2013; Sponsor: Amgen
  19. ClinicalTrials.gov Trial Identifier NCT00172042; Last verified: August 2011; Sponsor: Novartis Pharmaceuticals
  20. ClinicalTrials.gov Trial Identifier NCT00096265; Last verified: October 2011; Sponsor: National Cancer Institute (NCI)
  21. ClinicalTrials.gov Trial Identifier NCT00687297; Last verified: November 2012; Sponsor: PrECOG, LLC
  22. ClinicalTrials.gov Trial Identifier NCT00098254; Last verified: April 2012; Sponsor: National Cancer Institute (NCI)
  23. ClinicalTrials.gov Trial Identifier NCT00473889; Last verified: November 2013; Sponsor: Merck Sharp & Dohme Corp
  24. ClinicalTrials.gov Trial Identifier NCT00499447; Last verified: January 2014; Sponsor: Comprehensive Cancer Center of Wake Forest University
  25. ClinicalTrials.gov Trial Identifier NCT00614484; Last verified: April 2014; Sponsor: Loma Linda University
  26. ClinicalTrials.gov Trial Identifier NCT00538850; Last verified: January 2014; Sponsor: INSYS Therapeutics Inc
  27. ClinicalTrials.gov Trial Identifier NCT00871403; Last verified: March 2012; Sponsor: GlaxoSmithKline

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