The combination of immunotherapy agents nivolumab (Opdivo) and low-dose ipilimumab (Yervoy) offered improved overall survival (OS) compared with chemotherapy as a first-line treatment for advanced non–small cell lung cancer (NSCLC), according to the results of a new phase III study. The results could be practice-changing, but some work on patient selection and optimizing of combinations is still needed.
“Nivolumab and ipilimumab present with distinct but complementary mechanisms of action,” said Solange Peters, MD, PhD, of the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, adding that the combination has already been shown to be effective in other malignancies, including renal cell carcinoma and melanoma.
Peters presented results of the new study at the European Society for Medical Oncology (ESMO) 2019 Congress, held September 27 to October 1 in Barcelona, Spain.
The CheckMate-227 trial included a total of 1189 patients with chemotherapy-naive stage IV or recurrent NSCLC without EGFR or known ALK alterations. Patients who were considered PD-L1-positive (≥1%) were randomized to 1 of 3 treatment groups: nivolumab plus low-dose ipilimumab (396 patients); nivolumab alone (396 patients); or chemotherapy alone (397 patients).
After a minimum follow-up of 29.3 months, (OS) was significantly better with the immunotherapy combination than with chemotherapy. The median OS was 17.1 months with nivolumab and ipilimumab, compared with 14.9 months with chemotherapy, for a hazard ratio (HR) of 0.79 (97.72% CI, 0.65-0.96; P = 0.007). The median OS with nivolumab alone was 15.7 months, for an HR compared to chemotherapy of 0.88 (95% CI, 0.75-1.04).
The combination therapy also performed better with regard to progression-free survival, objective response rates, and the duration of response in patients who were PD-L1-positive.
In a small analysis of patients with PD-L1 expression below 1%, the results were similar. The median OS in 187 such patients treated with nivolumab plus ipilimumab was 17.2 months, compared with 12.2 months in 186 patients treated with chemotherapy. The OS benefit was seen in an analysis of the entire cohort as well, combining the PD-L1-positive and -negative patients.
In the full cohort, grade 3-4 treatment-related adverse events occurred in 33% of patients who received nivolumab plus ipilimumab, 19% of those treated with nivolumab alone, and in 36% of those who received chemotherapy.
“In my opinion these data are practice changing,” Peters said, according to a press release.
During her presentation at ESMO, she added “The dual immunotherapy represents a new first-line treatment option for patients with advanced NSCLC.”
Marina Chiara Garassino, MD, of the Istituto Nazionale dei Tumori in Milan, Italy, commented on the study for ESMO, said that this does represent a new treatment option for advanced NSCLC.
“We don’t yet know if the findings are practice changing,” she said. “We need to understand which treatment is best for each patient.”
She also noted that the study was initiated before immunotherapy-chemotherapy combinations were approved in this setting, so the nivolumab-ipilimumab combination was not compared to current standards of care.