Novel combo therapy trumps chemo in NSCLC survival

By Naveed Saleh, MD, MS, for MDLinx
Published November 7, 2019

Key Takeaways

Combining nivolumab with low-dose ipilimumab could make for a novel first-line chemotherapy-free treatment for patients with advanced non-small cell lung cancer (NSCLC), according to results from the phase 3 CheckMate-227 trial presented at the European Society for Medical Oncology (ESMO) Congress 2019, hosted in Barcelona, Spain, September 27–October 1, 2019.

“In my opinion, these data are practice changing,” said lead author Solange Peters, MD, PhD, Oncology Department, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, and ESMO president-elect. “CheckMate-227 is the first trial showing that the combination of nivolumab and ipilimumab prolongs survival as compared to chemotherapy in treatment-naïve patients with metastatic NSCLC. We already have several front-line treatment options for these patients, including chemotherapy combined with an anti-PD1 agent or an anti-PDL1 agent alone. And now we have a chemotherapy-sparing option of nivolumab plus ipilimumab.”

In the CheckMate-227 trial, Dr. Peters and colleagues recruited chemotherapy-naïve patients with stage IV or recurrent NSCLC without EGFR or ALK mutations who had ECOG Performance Status scores of 0–1. In total, 1,189 patients with programmed death-ligand 1 (PD-L1) ≥ 1% were randomly assigned 1:1:1 to receive either: nivolumab 3 mg/kg every 2 weeks (Q2W) plus ipilimumab 1 mg/kg every 6 weeks (Q6W); nivolumab 240 mg Q2W; or chemotherapy alone. Additionally, 550 patients with PD-L1 < 1% were randomly assigned 1:1:1 to receive either: nivolumab 3 mg/kg Q2W plus ipilimumab 1 mg/kg Q6W; nivolumab 360 mg every 3 weeks plus chemotherapy; or chemotherapy alone.

Overall survival was significantly longer with nivolumab plus low-dose ipilimumab compared with chemotherapy alone in all patients. Progression-free survival, duration of response, and objective response rates were also higher in patients who received the combined immunotherapy option vs chemotherapy alone.

Patients with PD-L1 ≥ 1% who received nivolumab plus ipilimumab experienced a median overall survival of 17.1 months vs 14.9 months among those who received chemotherapy alone (HR: 0.79; 97.72% CI: 0.65–0.96, P = 0.007).

The rate of grade 3–4 adverse events among patients who received the immunotherapy combination was 33%, 36% in those who received chemotherapy, and 19% in those who received nivolumab.

Dr. Peters and fellow researchers noted that one limitation of their study was that it began before either chemotherapy/immunotherapy or immunotherapy on its own was approved as first-line treatment for NSCLC. Thus, the immunotherapy combination could not be stacked up against current standards of care. In other words, no treatment arm involving chemotherapy plus nivolumab was tested in the PD-L1–positive group. Nevertheless, according to exploratory analysis, the nivolumab-ipilimumab combination outperformed nivolumab monotherapy, which in turn outperformed chemotherapy in this group. The immunotherapy combination was more effective than nivolumab plus chemotherapy in PD-L1– negative patients, too.

Looking forward, Dr. Peters said, “The important step now is to develop an algorithm to select the best front-line treatment for each patient. We need to wait for a little more time to see which treatment really gives rise to improved long-term survival. The 5-year survival from trials with these treatments will teach us if any of the options are better than others. The second critical point will be to compare toxicities. We can then have an informed discussion with our patients.”

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