Given the beneficial PFS, the low toxicity rate, and the high responses in the brain, it’s a pretty easy drug to use in the first-line setting. However, there are many questions that are unanswered about how long patients will live. Will patients live longer and better? At the end of the day, these patients expect to have multiple options and to have good quality of life for a long period of time—and we have to help them get there.
Durvalumab (Imfinzi) was another interesting agent seen in the PACIFIC trial this year. Can you comment?
Durvalumab is not yet approved for lung cancer; we anticipate an approval based on the PACIFIC trial and the improvement in PFS, which was dramatic for patients who have locally advanced NSCLC following chemotherapy and radiation. The data are impressive, and it will be easy to use once we have approval. We anticipate that approval given the very highly positive results.
What combination regimens are being looked at currently that seem promising?
Today, there are multiple combinations that are being evaluated. Lung cancer is different than melanoma; we haven’t seen the same benefit with the CTLA-4/PD-1 or PD-L1 combinations. The toxicity in patients with lung cancer may be less tolerable because of comorbidities that these patients have, so this is still playing out.
Outside of CTLA-4, most of the other combinations are all in the running. We have to do better because response rates are still 20% or less when we use single-agent [immunotherapy] in the first-line setting. When [a patient is] highly selective, it may be closer to 50%; however, that is still a large number of patients who don’t respond. We need to do better. I don’t think there is a clear winner in terms of combinations today.
What are the biggest remaining challenges in the field of lung cancer?
The biggest challenges are resistance—resistance to immunotherapy and resistance that develops to targeted therapy. We need to overcome that because we have great therapies and more patients respond and live longer, but our patients don’t live forever so we are not curing this disease and we have a long way to go.
The second biggest challenge is cost and, as we have come forward with more new therapies, the cost may be prohibitive and we need to find a way, again, to get more people the right therapies to help them live longer and better. However, there is a huge cost associated with that—with testing and with treatments.
How would you describe 2017 as a pivotal year for lung cancer treatment?
The biggest advancements in 2017 would be looking at more effective first-line agents as we saw with alectinib (Alecensa) for ALK
-positive disease and osimertinib for EGFR-mutant disease, and starting to learn how to better sequence them but also provide more efficacy with less toxicity for patients. For patients with BRAF
mutations, we now have an FDA-approved combination.
Then, the advance of immunotherapy [went] even further; now we have it available in the first-line setting. Clearly, immunotherapy changes the biology of the disease as we see patients have better survival. This is despite the fact that even patients who potentially get chemotherapy in the first-line setting and would get second-line immunotherapy still had lesser survival than those who got it in the first-line setting. There is a clear change in the biology, so the frontier in front of us has a clear vision to try and understand that because, if we can change that biology for more people, we may help more people live longer.