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Recent advances with immune checkpoint inhibitors could improve outcomes for patients with squamous cell non-small cell lung cancer, a traditionally hard to treat histology.
Benjamin P. Levy, MD
Recent immune checkpoint inhibitor advancements could improve outcomes for patients with squamous cell non-small cell lung cancer, a traditionally hard to treat histology, explained Benjamin P. Levy, MD, in an interview with OncLive.
Levy, the director, Thoracic Medical Oncology at Mount Sinai Beth Israel, and the associate director of Cancer Clinical Trials Office at Mount Sinai Hospital, recently sat down with OncLive to discuss updates in the field of squamous cell lung cancer.Levy: I think we’re in a real time of excitement with immunotherapeutic approaches in lung cancer. There are multiple agents being looked at. The unique thing about these drugs is that they harness the patient’s own immune system against the cancer.
We found out recently that one of the drugs, nivolumab, has a very good outcomes reported from the CheckMate-063 Study. This study looked specifically at squamous cell patients who had progressed on multiple lines of chemotherapy. By instituting nivolumab, we saw a response rate of around 15%. Keep in mind that historically response rates in this setting are around 5-10%. A 1-year survival rate of over 40% was also observed in these patients, which is unprecedented. Historical controls would suggest this number to be around 10-15% at 1-year. We saw 40%.
I don’t think we know who the patients that are most likely to respond are yet. The biomarker search is on to define molecularly who the patients are that are going to garner the most benefit. Nevertheless, it’s tremendously exciting to see these drugs at work and we are excited to see where these drugs will fit into the non-small cell lung cancer treatment paradigm.I think there’s been a lot of searching for actionable mutations in lung cancer, specifically in non-small cell lung cancer adenocarcinoma. We’ve identified patients who have EGFR mutations and ALK mutations and for these patients, we can deliver TKIs and we’ve witnessed unprecedented outcomes. I think what we have to remember is that for the large majority of our patients, we don’t have targeted therapies and we have to default to chemotherapy.
What we know is that chemotherapy improves survival in the advanced stage setting and it also improves quality of life. I think we have to remain grounded that not all patients have actionable mutations, and in fact a large majority of them don’t, and I think for that that patient population, we should really be advocates for systemic chemotherapy but I also think we have to be realistic about the benefits of systemic chemotherapy.
I think one of the new treatment paradigms is the role of maintenance chemotherapy in non-small cell lung cancer for patients who at least do well and achieve stable disease after 4 cycles of platinum chemotherapy. I think what we know is that if patients are doing well on chemotherapy, they should stay on chemotherapy. You should probably drop the platinum and continue drugs like pemetrexed, which have shown survival advantages in multiple studies.
The take home point is that, yes, we have actionable mutations for lung cancer; yes, we have targeted drugs for those actionable mutations. However, most of our patients we have to default to chemotherapy and for that patient population we should be offering systemic chemotherapy. The goal should be realistic, but I also think we should be talking about maintenance chemotherapy for these patients. Maintenance chemotherapy has been looked at for many years but up until recently, hasn’t shown a survival advantage. What we’ve learned in the past 5 years is that maintenance chemotherapy for patients in non-small cell lung cancer works, specifically pemetrexed. There have been two studies looking at maintenance pemetrexed as a treatment approach. One was a switch maintenance study and the other was the PARAMOUNT data.
What we saw in both of those studies was that maintenance pemetrexed improves survival. The PARAMOUNT study improved survival by 3 months. This should be put into the context that many non-small cell lung cancers studies don’t show a survival advantage.
Based on these studies, maintenance chemotherapy should be discussed with our patients. I think we should have that discussion at the beginning of treatment rather than at the time that they’re about to receive treatment. Not all patients are going to do well on maintenance chemotherapy so this is a discussion that has to happen and the conversation needs to happen in the beginning, to discuss the benefits of maintenance chemotherapy.Squamous cell non-small cell lung cancer has historically been more difficult to treat. It seems to be more refractory to chemotherapy and the mutational load of squamous cell makes it resistant to certain therapies. Because of this, squamous cell has become important to focus on so we can really try to advance squamous cell the way we’ve advanced adenocarcinoma.
One of the techniques has been immunotherapy. The CheckMate-063 study looked at nivolumab, specifically in squamous cell and as a third-line agent, demonstrated competitive outcomes.
The Lung-MAP study is a study that is specifically looking at squamous cell. Patients who have progressed on platinum chemotherapy are genetically profiled and then they’re randomized to different arms based on the biomarker that is discovered during the profiling.
Hopefully we’ll have some better targeted drugs for this patient populations.