Summary
Findings from the phase III CheckMate-9LA trial demonstrated that nivolumab plus ipilimumab, given concomitantly with 2 cycles of chemotherapy, had a statistically significant and clinically meaningful survival benefit as a first-line treatment of metastatic non-small cell lung cancer (NSCLC).
The study, which met both its primary and key secondary endpoints, showed superior overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) for the immunotherapy plus chemotherapy combination compared to chemotherapy alone, according to data presented at the 2020 ASCO Annual Meeting (Abstract 9501).
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Original Article
Immunotherapy Combo Plus Chemo Improves Survival in First-Line NSCLC
Oncology Times
By Catlin Nalley
Findings from the phase III CheckMate-9LA trial demonstrated that nivolumab plus ipilimumab, given concomitantly with 2 cycles of chemotherapy, had a statistically significant and clinically meaningful survival benefit as a first-line treatment of metastatic non-small cell lung cancer (NSCLC).
The study, which met both its primary and key secondary endpoints, showed superior overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) for the immunotherapy plus chemotherapy combination compared to chemotherapy alone, according to data presented at the 2020 ASCO Annual Meeting (Abstract 9501).
“The nivolumab plus ipilimumab combination has been shown to increase survival in patients with first-line non-small cell lung cancer, and adding a limited course of chemotherapy may help mitigate the risk of early disease progression,” said study author Martin Reck, MD, PhD, Lung Clinic Grosshansdorf, German Center for Lung Research, in a statement.
“With these results from CheckMate-9LA, we now have evidence that this dual immunotherapy combination, when administered concomitantly with 2 cycles of chemotherapy, provides a survival benefit in this setting—a benefit that was observed early and sustained at 1 year of follow-up across key subgroups of patients,” he noted. “As the data become more mature, I see the potential for an improving survival benefit over time.”
Based on findings from CheckMate-9LA, the FDA recently approved nivolumab plus ipilimumab with 2 cycles of platinum-doublet chemotherapy as a first-line treatment for patients with metastatic or recurrent NSCLC, with no EGFR or ALK genomic tumor aberrations.
Study Methodology
CheckMate-9LA is a phase III randomized study evaluating nivolumab plus ipilimumab combined with 2 cycles of chemotherapy versus chemotherapy alone in first-line stage IV/recurrent NSCLC.
The researchers hypothesized that a “limited course of chemotherapy combined with nivolumab plus ipilimumab could provide rapid disease control while building on the durable OS benefit seen with dual PD-1 and CTLA-4 inhibition.”
Adults with treatment-naive, histologically confirmed stage IV/recurrent NSCLC with an ECOG performance status of 0-1, and no known EGFR/ALK alterations were randomized 1:1 to receive nivolumab (360 mg Q3W) and ipilimumab (1 mg/kg Q6W) plus chemotherapy (2 cycles) (n = 361) or chemotherapy (4 cycles) alone (n = 358). Patients were stratified by PD-L1 (< 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous).
Chemotherapy was based on histology, according to the study authors, who noted that patients with non-squamous NSCLC in the chemo-only arm could receive optional pemetrexed maintenance.
Patients underwent immunotherapy until disease progression, unacceptable toxicity, or for 2 years. OS was the primary endpoint. Secondary objectives included PFS and ORR by blinded independent central review, and efficacy by PD-L1 subgroups. Exploratory endpoints were safety/tolerability.
Key Findings
Across both arms, baseline patient characteristics were balanced. At the interim analysis (minimum follow-up 8.1 months), the researchers found that OS was significantly prolonged with nivolumab plus ipilimumab in combination with chemotherapy compared to chemotherapy alone (HR 0.69, 96.71% CI: 0.55–0.87; P = 0.0006). They also reported statistically significant improvements in PFS and ORR.
Additionally, with longer follow-up (minimum 12.7 months), dual immunotherapy and chemotherapy regimen continued to sustained OS improvements over chemotherapy alone (median OS of 15.6 months vs. 10.9 months). The clinical benefit was observed across all efficacy measures in key population subgroups, including PD-L1 expression and tumor histology.
In terms of safety, 47 percent of patients in the combination arm reported grade 3-4 treatment-related adverse compared to 38 percent in the chemotherapy only group.
“We have observed comprehensive improvement in all efficiency endpoints, including response, progression-free, and overall survival,” Reck said. “Furthermore, with additional follow up, there is an improvement in overall survival, favoring the combination.”
With these findings, he noted, “we now have a very active combination available for patients with untreated NSCLC,” he continued. “This combination works across the disease subgroups that we do see every day. It works across histologies and different PD-L1 expression stages, as well as independently from gender and ethnicity. So, what we have in hand now is a powerful new combination for the first-line treatment of NSCLC patients without any oncogenic alterations.”
Next steps include further follow-up, as well as a closer look at tolerability. “Does the intensity of this combination have any effect on the quality of life?” noted Reck. “We are preparing an abstract for the ESMO conference on patient-reported outcomes and quality-of-life data. This is a very important question when you transfer these observations into clinical medicine.
Another area that requires further investigation is the amount of chemotherapy needed to generate these benefits. “The question is, do we really need 2 cycles? Or are we able to reduce this dose of chemotherapy, which is always associated with some toxicities?” Reck concluded. “This is also a very important area of research that we are focusing on.”
Catlin Nalley is a contributing writer.