Bevacizumab in Nonsquamous Lung Cancer

Transcript:Marina Garassino, MD: The approved indication for bevacizumab is firstly in adenocarcinoma and in combination with chemotherapy, in particular with carboplatin and Taxol. This is based on an important trial published in New England Journal of Medicine several years ago by Sandler, and we know that this was the drug that gave survival benefit in treating adenocarcinoma patients. Unfortunately, the story in Europe was slightly different because we had a European trial using the bevacizumab added to cisplatin and gemcitabine, and this trial was negative.

In the next years, the combination of cisplatin and pemetrexed appeared on the market. In Europe, generally, we prefer to use the combination of cisplatin and pemetrexed. But, carboplatin/Taxol and bevacizumab still is a really important strategy to treat these kinds of patients. It’s important to underline that it’s only for patients with adenocarcinoma, and they need to have peripheral lesions and no uncontrolled hypertension.

Roy S. Herbst, MD, PhD: Bevacizumab is a drug we’ve been studying for 20 years in lung cancer. It’s an anti-angiogenic drug. It’s an antibody against VEGF, vascular endothelial growth factor. It’s been shown to improve survival in combination with carboplatin/paclitaxel versus carboplatin/paclitaxel alone, in the ECOG-4599 trial, with a hazard ratio of 0.8. Oftentimes, if I use carboplatin/Taxol in lung cancer, it’s in someone who has nonsquamous lung cancer and they have no contraindications to the anti-angiogenic agent, meaning they have no bleeding. I would use it in that setting. Nowadays, people have moved towards using carboplatin/pemetrexed as a frontline chemotherapy for lung cancer. And the additional benefit of bevacizumab with that combination is somewhat debatable. If someone has excellent performance status, absolutely no contraindications to an anti-angiogenic, I tend to use the triplet therapy: carboplatin/pemetrexed with bevacizumab. But, I know that in the community and other countries, people have tended to use just a doublet, carboplatin/pemetrexed, usually followed by pemetrexed maintenance.

Joachim G. Aerts, MD, PhD: Anti-angiogenic agents, like bevacizumab, have been available for many years now. We use it as a first-line treatment in patients with nonsquamous non—small cell lung cancer, and in general in combination with taxanes. We have some scientific evidence that the anti-angiogenic agents work better in combination with taxanes because taxanes could have a special effect on the endothelial cells, which are increased by the anti-angiogenic agents.

In our clinical practice in Holland, in my country, bevacizumab is not that regularly used because we have other regimens that are not taxane based, and that’s why we need a combination with anti-angiogenic agents. But, there are some preclinical data, or early clinical data, showing that maybe some patients with different kinds of mutations, for instance, KRAS mutations, may do better on that kind of treatment. So, that’s something that is now under investigation and also one of the reasons why we use it in that setting.

Enriqueta Felip, MD, PhD: Bevacizumab is a drug that we use in patients with nonsquamous histology— patients with a stage 4 disease. In my clinical practice, I am using bevacizumab in a number of patients with an ECOG performance status 0 or 1, a nonsquamous histology without previous hemoptysis and without tumors in a central location with invasion of great vessels. We prescribe the drug in combination with a platinum doublet, and the usual treatment is 4 cycles of chemotherapy plus bevacizumab followed by bevacizumab alone as maintenance.

I am treating a number of patients with EGFR mutations who progress on initial EGFR-TKIs. And at rebiopsy, we are unable to find the T790M mutation. For these patients, sometimes, I also prescribe a chemotherapy plus bevacizumab.

Marina Garassino, MD: We decided there is no real difference among the 2 regimens—so, between cisplatin/pemetrexed and carboplatin/Taxol/bevacizumab—because there are no trials comparing the 2 regimens. There is only one trial saying that the quality of life, maybe, could be better with the combination of pemetrexed. So, generally, we decided to give carboplatin/Taxol/bevacizumab in patients in which we need a very short shrinkage of the disease because the response rate of this regimen is very high. But, again, I can say that there are no major differences between the 2 regimens.

Joachim G. Aerts, MD, PhD: Bevacizumab has been used as a first-line treatment in combination with chemotherapy in metastatic non—small cell lung cancer for many years now. But, we are also trying to introduce it in other settings. So, we have now seen a positive study where bevacizumab was used in combination with erlotinib in EGFR-mutant non–small cell lung cancer. And we saw that there was an increase in the activity of erlotinib when you combine it with the bevacizumab. That’s, again, a whole new field of treatment in patients in whom we didn’t intend to use it before. So, that’s a new concept that is coming into place.

And, the other thing is that we know that bevacizumab is used as a maintenance treatment after chemotherapy. So, you give them 4 or 6 cycles of chemotherapy, and then afterwards you continue with the bevacizumab. But, you have also some results showing that when you use cisplatin/pemetrexed, you can also use it in combination with bevacizumab. And then, when you continue on pemetrexed/bevacizumab as a maintenance, that’s probably more effective than the pemetrexed alone. These are all new results in a new concept, but we have to look at how to combine this to get the optimal treatment for the patients.

Transcript Edited for Clarity