Marina Chiara Garassino, MD
The treatment landscape of non–small cell lung cancer (NSCLC) has had a number of encouraging findings in the last 3 years, particularly with checkpoint inhibitors that target the PD-1/PD-L1 pathway.
Marina C. Garassino, MD, medical consultant, Medical Oncology Division, Fondazione IRCCS Istituto Nazionale dei Tumori, discussed the evolving paradigm of immunotherapy in NSCLC, with a specific focus on durvalumab and the role of combination therapy.
OncLive: What is the current role of immunotherapy in lung cancer?
: In the last 3 years, there was a big change in the paradigm of cancer care with immunotherapy. With the advance of immunotherapy now, we’ve changed the paradigm in several points of disease in patients with NSCLC, starting from stage III disease—which is the big novelty of this year with the PACIFIC trial. We also have several new drugs for the first-line treatment, in particular for patients with PD-L1 expression. The survival of patients treated with pembrolizumab (Keytruda) presented [at the IASLC 18th World Conference on Lung Cancer], was 30 months. Before it was about 17 months, so it really has radically changed the treatment of NSCLC.
We also have several drugs in the second-line treatment of patients with NSCLC. We have nivolumab for all comers, pembrolizumab for patients with PD-L1 more than 1%, and atezolizumab (Tecentriq) for all comers. Several other trials are starting in the neoadjuvant setting and the adjuvant setting.
What is the role of combination therapy in NSCLC?
We would really like to increase the number of patients still alive, and the promise is in combinations. In the future, treatment will be based on the immune phenotype, and we have at least 3 phenotypes right now: inflamed, immune excluded, and immune desert. According to the 3 phenotypes, we will be able to combine the first generation of immune checkpoint inhibitors with several other agents. Some of them could be an IDO inhibitor, but we also have TM3, GITR, and, again, chemotherapy. Chemotherapy can be a very important thing to add to the immune checkpoint inhibitors because it attacks the immune cycle of cancer. Therefore, we have several possibilities to increase the response rate, PFS, and OS.
Can you share your insight on the pivotal findings from the PACIFIC trial and how they will impact clinical practice?
The PACIFIC trial is a very important trial because it covers a huge unmet need for NSCLC, which is stage III locally advanced disease. The patients who are considered resectable were randomized to receive either durvalumab or placebo. The PFS was clearly in favor of patients who received the chemoradiation, and after chemoradiation they received durvalumab. There was an increase of more than 11 months PFS in treating patients with durvalumab for up to 1 year.
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