Corey Langer, MD
From optimal therapies for patients with non-driver adenocarcinoma, to studying the biology of squamous cell non–small cell lung cancer (NSCLC), to exploring novel combination regimens, to predicting the risk of mortality, the field of lung cancer is undergoing tremendous changes, explained Corey J. Langer, MD.
“The vast majority of patients with advanced NSCLC, unfortunately, do not have oncogenic drivers,” said Langer when discussing agents for patients with non-driver disease. “Those are confined to 20% to 30% of the group, and we have seen lots of promise for new agents based on the molecular target. However, the majority doesn’t have it.”
The expert shed light on all of these topics during the 2016 OncLive State of the Science Summit on Advanced Non-Small Cell Lung Cancer on September 17 in Philadelphia, Pennsylvania.
In an interview with OncLive
during the meeting, Langer, professor of Medicine at the Perelman School of Medicine, director of Thoracic Oncology, at the University of Pennsylvania, discussed non-driver adenocarcinoma, some of these new combination therapies in lung cancer, and plenty more.
OncLive: Can you provide an overview of your discussion on squamous NSCLC?
: We’re still in the era of systemic cytotoxics, and here, too, we have made some headway. In the last 10 or 12 years, we have seen distinctions histologically with the role of pemetrexed (Alimta) and bevacizumab (Avastin) clearly secured for nonsquamous NSCLC phase III trials that have shown a survival advantage for those agents in combination with platinum-based agents or platinum therapies and other cytotoxics that have proven superior. Really, that is our platform for nonsquamous disease.
For squamous, it’s been a far greater challenge. There are phase III histology-based data that show, for instance, that gemcitabine and platinum is superior to pemetrexed and platinum. Therefore, gemcitabine is certainly one of our go-to agents for those with squamous histology. Taxanes have also proven superior to pemetrexed in the second-line setting in squamous, so taxanes are generally used upfront.
We do have very interesting data looking at nanoparticle albumen-bound paclitaxel in combination with carboplatin which, compared to conventional solvent-based paclitaxel, has led to a significant improvement in response rate, although that hasn’t really translated into either a progression-free (PFS) or overall survival (OS) advantage in squamous cell.
It should be noted that in individuals over 70, there was an advantage. Again, it’s a retrospective analysis. It’s only 150 patients or so, but about an 8- or 9-month difference favoring the nanoparticle-bound taxane over the conventional standard co-solvent cremophor-based molecule.
Are there other agents that may have a benefit in squamous NSCLC?
There are data in the second-line setting combining ramucirumab (Cyramza), which is an angiogenesis inhibitor that targets the receptor on endothelial cells, in combination with docetaxel. Clearly, there is a survival advantage compared with standard chemotherapy alone. This was observed not just in adenocarcinoma, but also in squamous cell. It’s certainly an option in the second-line setting, and we have compelling data for an EGFR monoclonal antibody necitumumab (Portrazza) in combination with the gemcitabine regimen, which has led to a survival advantage in the frontline setting. The options are expanding, but not as quickly as nonsquamous.
What are some of the toxicities of some of these agents, either in combination or as monotherapies?
Pemetrexed compared with a taxane is generally less toxic. We don’t see the hair loss that’s typically associated with taxanes—much less neuropathy—and there is virtually no neuropathy with pemetrexed. We do see some rash, and sometimes gastrointestinal toxicity or myelosuppression.