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First-Line Chemotherapy Options in Lung Adenocarcinoma

Insights From:Anders Mellemgaard, MD, Herlev University Hospital; Sanjay Popat, PhD, FRCP, The Royal Marsden Hospital;Martin Reck, MD, PhD, Hospital Grosshansdorf
Published: Monday, Oct 31, 2016


Transcript:

Anders Mellemgaard, MD:
For metastatic pulmonary adenocarcinoma first-line therapy, there are a couple of choices. First of all, the experience has taught us that it’s best to use a two-drug combination, and one of the two drugs should be a platinum compound—cisplatin or carboplatin. Now, the second drug should be a third-generation chemotherapy compound, and that could be one of several: gemcitabine, vinorelbine, pemetrexed, or docetaxel. Even paclitaxel can be used. A third drug can sometimes be added as a biological agent; for example, bevacizumab. Bevacizumab in combination is also something that has been used frequently, mostly in combination with carboplatin, paclitaxel. So, most of the data we have are on that combination.

I don’t think we can say that any particular combination is better than the rest. But, a meta-analysis has shown that cisplatin is slightly more effective. It gives slightly better overall survival, but at a price of added toxicity. And, perhaps, pemetrexed is slightly better than the other third-generation compounds, also with respect to overall survival.

Guidelines for chemotherapy are quite simple because they say that it should be a doublet—a two-drug combination with a platinum compound—and a third-generation chemotherapy agent.

Martin Reck, MD, PhD: When I give my patients with advanced lung cancer chemotherapy, I have some assumption what I can expect from efficacy and, in particular, from response rate. And this is differentiated according to the histology of the tumor. So, we may expect a little bit more response in patients with non-squamous histology compared to the patients with squamous histology. Roughly, the response rate that I would expect in the one patient with a metastatic non–small cell lung cancer would be in the range of 30% to 35%. Furthermore, I would expect something like a tumor control rate in the range of 50% to 55% of my patients.

When we expect the response, of course we also would like to see duration of response. We want to see durable responses. In reality, the median progression-free survival (PFS) that we have observed in the trials is in the range between 6 to 7 months, and the duration of response is more or less in the same time of month that we may expect in our patients.

Sanjay Popat, PhD: The role of bevacizumab in patients without driving mutations in non-squamous non–small cell lung cancer is controversial. Bevacizumab is certainly licensed for use together with platinum-doublet chemotherapy in non-squamous tumors because it was developed in patients with non-squamous tumors with early toxicities, identified in the development of a program in patients with squamous tumors. We have data from two large trials, which demonstrated the survival advantage in combination with carboplatin and paclitaxel. So, therefore, bevacizumab is usually given in combination with carboplatin and Taxol. There is evidence of benefit, in terms of modest benefits in response rates, in progression-free survival in combination with cisplatin and gemcitabine, although that didn’t really translate to a survival benefit per se. Nevertheless, metro analyses and phase 4 analyses have demonstrated good outcomes in terms of overall survival when combining bevacizumab with other platinum-backbone cytotoxic chemotherapy compounds. And, indeed, it is licensed both by the FDA and EMA (European Medicines Agency) for use with other cytotoxic third-generation compounds, including pemetrexed, although there’s never been any head-to-head trial of bevacizumab with or without its use in a platinum-pemetrexed backbone-based study.

Transcript Edited for Clarity
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Transcript:

Anders Mellemgaard, MD:
For metastatic pulmonary adenocarcinoma first-line therapy, there are a couple of choices. First of all, the experience has taught us that it’s best to use a two-drug combination, and one of the two drugs should be a platinum compound—cisplatin or carboplatin. Now, the second drug should be a third-generation chemotherapy compound, and that could be one of several: gemcitabine, vinorelbine, pemetrexed, or docetaxel. Even paclitaxel can be used. A third drug can sometimes be added as a biological agent; for example, bevacizumab. Bevacizumab in combination is also something that has been used frequently, mostly in combination with carboplatin, paclitaxel. So, most of the data we have are on that combination.

I don’t think we can say that any particular combination is better than the rest. But, a meta-analysis has shown that cisplatin is slightly more effective. It gives slightly better overall survival, but at a price of added toxicity. And, perhaps, pemetrexed is slightly better than the other third-generation compounds, also with respect to overall survival.

Guidelines for chemotherapy are quite simple because they say that it should be a doublet—a two-drug combination with a platinum compound—and a third-generation chemotherapy agent.

Martin Reck, MD, PhD: When I give my patients with advanced lung cancer chemotherapy, I have some assumption what I can expect from efficacy and, in particular, from response rate. And this is differentiated according to the histology of the tumor. So, we may expect a little bit more response in patients with non-squamous histology compared to the patients with squamous histology. Roughly, the response rate that I would expect in the one patient with a metastatic non–small cell lung cancer would be in the range of 30% to 35%. Furthermore, I would expect something like a tumor control rate in the range of 50% to 55% of my patients.

When we expect the response, of course we also would like to see duration of response. We want to see durable responses. In reality, the median progression-free survival (PFS) that we have observed in the trials is in the range between 6 to 7 months, and the duration of response is more or less in the same time of month that we may expect in our patients.

Sanjay Popat, PhD: The role of bevacizumab in patients without driving mutations in non-squamous non–small cell lung cancer is controversial. Bevacizumab is certainly licensed for use together with platinum-doublet chemotherapy in non-squamous tumors because it was developed in patients with non-squamous tumors with early toxicities, identified in the development of a program in patients with squamous tumors. We have data from two large trials, which demonstrated the survival advantage in combination with carboplatin and paclitaxel. So, therefore, bevacizumab is usually given in combination with carboplatin and Taxol. There is evidence of benefit, in terms of modest benefits in response rates, in progression-free survival in combination with cisplatin and gemcitabine, although that didn’t really translate to a survival benefit per se. Nevertheless, metro analyses and phase 4 analyses have demonstrated good outcomes in terms of overall survival when combining bevacizumab with other platinum-backbone cytotoxic chemotherapy compounds. And, indeed, it is licensed both by the FDA and EMA (European Medicines Agency) for use with other cytotoxic third-generation compounds, including pemetrexed, although there’s never been any head-to-head trial of bevacizumab with or without its use in a platinum-pemetrexed backbone-based study.

Transcript Edited for Clarity
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