Squamous NSCLC Treatments Incorporating Immunotherapy Combinations

Ipilimumab/Nivolumab Improves Survival in NSCLC Regardless of PD-L1 Status

Martin Dietrich, MD, PhD, discusses the study design and results of the CheckMate 9LA trial of ipilimumab and nivolumab for patients with non–small cell lung cancer.

Martin Dietrich, MD, PhD, medical oncologist at Florida Cancer Specialists and Research Institute and assistant professor of Internal Medicine at the University of Central Florida, discusses the study design and results of the CheckMate 9LA trial (NCT03215706) of ipilimumab (Yervoy) and nivolumab (Opdivo) for patients with non–small cell lung cancer (NSCLC).

The previous phase 3 CheckMate 227 trial (NCT02477826) compared the combination of ipilimumab, nivolumab, and up to 4 cycles of chemotherapy versus nivolumab plus chemotherapy or chemotherapy alone, while the CheckMate 9LA trial combined ipilimumab, nivolumab, and 2 cycles of chemotherapy versus chemotherapy alone.

According to Dietrich, the combination of dual PD-L1 and CTLA-4­–targeted immunotherapy plus chemotherapy was designed to induce a strong response early on in treatment to maximize the long-term survival benefit for more patients.

CheckMate 9LA demonstrated significant improvement in overall survival (OS) not only for patients with PD-L1 expression of 50% or greater, but for those with PD-L1 expression of 1% to 50% and PD-L1 expression below 1%, which was also observed in CheckMate 227. Patients with PD-L1 expression below 1% who received the combination had a median OS of 16.8 months versus 9.8 months with chemotherapy alone. Those with positive PD-L1 expression also had an OS benefit of 5 to 6 months. Dietrich says this suggests an absolute benefit for immunotherapy in the first-line setting.

TRANSCRIPTION:

0:08 | The CheckMate 9LA trial built on CheckMate 227, which was an evaluation of combination approaches in immunotherapy in the first-line NSCLC setting. It's very clear that even though we've made progress in the long-term outcomes, there's significant amount of room for improvement and that only a small percentage of patients really do benefit with long-term benefits. So the idea was, is the induction of a more aggressive immune response helpful and feasible and [would it] actually induce a longer-lasting responses in this trial, too?

CheckMate 9LA compared combination immunotherapy plus chemotherapy [with] chemotherapy alone. So it should be seen in context with [CheckMate] 227 where we had a more clear distinction between what the impact is of the individual immunotherapies both in the PD­-L1–positive and the PD-L1–negative space. But what we've seen very clearly across the spectrum for the CheckMate 9LA patients—both for PD-L1 positives and PD-L1 negatives—[are]…very similar survival outcomes; [this is] suggesting something that we haven't seen before, which is a very similar absolute benefit for immunotherapy in the first-line setting.