Transcript:Solange Peters, MD, PhD: Before PACIFIC was performed, immunotherapy had already kind of reached the level of standard of care in advanced disease. In the recent 5 years, I would say in lung cancer—a little bit longer in melanoma; maybe 10 years in melanoma—immunotherapy has been shown to be able to really improve the outcome of patients who suffer from metastatic disease, a palliative setting. In lung cancer, it started with late-line treatment, second-line treatment moving to frontline treatment. But in this scenario, in my opinion, every patient with advanced non—small cell lung cancer should receive immunotherapy at some point, because it really improves the outcome and allows for a long-term benefit in a small but significant proportion of patients.

Marina Chiara Garassino, MD: We have now 3 drugs for the second- and third-line treatment of non—small cell lung cancer. The drugs are nivolumab and atezolizumab for all-comers—so, you can administer the drug independently by the PD-L1 expression—and you have also pembrolizumab, which is approved for patients with a PD-L1 of more than 1%. So, if you select with the PD-L1 expression or not, there are things in favor of these and things against. What is clear is that there are several evidences that all the drugs work in patients with a PD-L1 less than 50%. And I have also, in my personal experience, seen patients with PD-L1 have a very negative experience with very long-lasting responses. So, I think that the use of PD-L1 in the second-line setting is not as mandatory as in first-line treatment.

What I think can be important is the history of smoking among the patients. Because if you look at the subgroup analysis of all the clinical trials, you can observe in all the clinical trials that patients, never smokers, benefit less with immunotherapy compared with patients who are current smokers or former smokers. So, the use of immunotherapy in the second-line setting for patients, never smokers, must be discussed with the patients because, potentially, they have other treatment options such as, for example, docetaxel plus antiangiogenics or something like that. There is no clear benefit of this kind of patient with immunotherapy.

We have 2 important randomized clinical trials suggesting that there is also a role of docetaxel plus antiangiogenics. The 2 drugs are ramucirumab and nintedanib, and they work better than docetaxel alone. So, this is another important option for second-line treatment in non—small cell lung cancer.

When we decide to use immunotherapy or the combination of these 2 drugs is another open question, because there are no randomized clinical trials comparing the 2 strategies. So, this is an important decision that must be shared with the patients, because the combination of chemotherapy plus antiangiogenics is totally different from immunotherapy. But it can be an important option for patients who have an early progression with the first-line treatment, because we have, in all the subgroup analyses, the idea that patients with early progression can benefit more from chemotherapy plus the antigen. So, we can decide to go with chemotherapy, chemotherapy plus antiangiogenics, and then immunotherapy as a third-line option. Or we can go with the first-line chemotherapy, immunotherapy, and then to leave again the chemotherapy as a third-line option.

There are no clear answers to these questions, so I think that we have to share the decisions with the patients, patient by patient, according to the toxicities and also with the expectations that we have from the drugs.