CheckMate 9LA: Long-Term Benefits of Immunotherapy and Chemotherapy in Advanced Lung Cancer
- New 6-year overall survival (OS) data from the phase 3 CheckMate 9LA trial (nivolumab plus ipilimumab with or without chemotherapy) demonstrate a sustained benefit with the addition of...
- Clinically significant findings were also seen among patients with tumor PD-L1 expression below 1%-a population that has historically represented a major therapeutic challenge.
- The 6-year findings showed that patients with PD-L1 expression of less than 1% had an OS rate of 20% compared with 7% for those treated with chemotherapy alone...
Six-year data for CheckMate 9LA (NCT03215706) continued to show benefits for patients with metastatic non-small cell lung cancer (NSCLC) who had received dual immune checkpoint inhibition plus chemotherapy.
This final analysis, which appeared in ESMO Open on May 29, 20251, had a minimum follow-up of 68.6 months. Findings showed that initial treatment with nivolumab (Opdivo) and ipilimumab (Yervoy), both from Bristol Myers Squibb, plus chemotherapy delivered a 26% overall survival (OS) benefit over that time compared with chemotherapy alone, with notable results for patients whose tumors were PD-L1 negative, making them difficult to treat.2
Study Design and patient Population
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Long-Term Survival Data From CheckMate 9LA Trial
New 6-year overall survival (OS) data from the phase 3 CheckMate 9LA trial (nivolumab plus ipilimumab with or without chemotherapy) demonstrate a sustained benefit with the addition of a short course of chemotherapy to dual immunotherapy in patients with advanced non-small cell lung cancer (NSCLC). The findings, presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, showed that the benefit was maintained irrespective of tumor histology. In patients with squamous NSCLC, 6-year OS rates were 14% with the combination vs 5% with chemotherapy (HR, 0.65; 95% CI, 0.49-0.85). For nonsquamous histology, the results were 17% vs 12% (HR, 0.79; 95% CI, 0.65-0.96). The greater magnitude of benefit observed in squamous NSCLC is noteworthy, as these patients typically have limited treatment options and poorer prognoses.5
encouraging Results Seen in PD-L1-Negative Patients
Clinically significant findings were also seen among patients with tumor PD-L1 expression below 1%-a population that has historically represented a major therapeutic challenge. These patients have tumors that don’t strongly express the PD-L1 protein, making them less responsive to single-agent PD-1/PD-L1 inhibitors, which rely on “uncloaking” cancer cells for immune system recognition. Without targetable driver mutations, these patients have been left with chemotherapy combined with immunotherapy as a common strategy, though this approach has typically yielded limited long-term benefits.2
The 6-year findings showed that patients with PD-L1 expression of less than 1% had an OS rate of 20% compared with 7% for those treated with chemotherapy alone (HR, 0.64; 95% CI, 0.49-0.84), representing a nearly 3-fold difference in long-term survival. The median OS was 17.7 months vs 9.8 months, respectively, demonstrating both early and sustained benefit.1,4
For patients with PD-L1 expression of at least 1%, 6-year OS rates were 15% with the dual immunotherapy combination vs 10% with chemotherapy alone (HR, 0.75; 95% CI, 0.61-0.92), with a median OS of 15.8 months vs 10.9 months. Although the absolute benefit was smaller in this subgroup than in patients with PD-L1 expression of less than 1%, the combination regimen still demonstrated consistent efficacy across the PD-L1 expression spectrum.
“The addition of a short course of chemotherapy to nivolumab plus ipilimumab appeared to provide greater response benefit [than] nivolumab plus ipilimumab,” the authors note in thier discussion of the results. “In the phase 3 CheckMate 227 study,6 [overall response rates] with nivolumab plus ipilimumab were 27% in patients with tumor PD-L1 < 1% and 36% in patients with tumor PD-L1 ≥1% compared with 31% and 43% with nivolumab plus ipilimumab with chemotherapy in the respective tumor PD-L1 expression subgroups in CheckMate 9LA.”1
The authors further note, “Long-term survival outcomes were similar between the 2 immunotherapy-based regimens, however, with 6-year OS rates of 16% and 22% with nivolumab plus ipilimumab in the tumor PD-L1 <1% and PD-L1 ≥1% subgroups…of CheckMate 227, respectively, compared with 20% and 15%, respectively, with nivolumab plus ipilimumab with chemotherapy in the current study.”1
“By simultaneously targeting both PD-1 and CTLA-4
Nivolumab, Ipilimumab, and Chemotherapy as First-Line Treatment for Metastatic NSCLC
Data from the six-year follow-up of the CheckMate 9LA trial demonstrate that nivolumab combined with ipilimumab and chemotherapy provides durable benefits as a first-line treatment for metastatic non-small cell lung cancer (NSCLC). The regimen shows particular efficacy in patient subgroups historically associated with poorer outcomes, including those with low PD-L1 expression and squamous histology.
Efficacy and Durability of Response
The CheckMate 9LA trial established nivolumab plus ipilimumab with chemotherapy as a highly effective standard-of-care option for first-line treatment of metastatic NSCLC. The study highlights the durability of clinical benefit achieved through the combination of dual immune checkpoint inhibition and chemotherapy. Specifically, the median duration of response (DOR) was 20.3 months with the nivolumab/ipilimumab/chemotherapy combination, compared to 16.3 months with platinum-doublet chemotherapy alone,as reported in the New England Journal of Medicine on October 26, 2023.
Impact on Patient Subgroups
This treatment combination delivers durable benefits across various patient subgroups. It is especially impactful for patients with PD-L1 levels less than 1%, a population that has historically experienced limited success with other therapies, and those with squamous histology NSCLC. The overall survival (OS) benefit was observed across all PD-L1 expression levels, with a hazard ratio of 0.77 (95% CI, 0.65-0.91) favoring nivolumab plus ipilimumab and chemotherapy, according to data presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #90811).
Clinical Trial Details and Results
CheckMate 9LA was a Phase 3, randomized, controlled trial involving 718 patients with metastatic NSCLC.Patients were randomized 1:1 to receive either nivolumab plus ipilimumab with platinum-doublet chemotherapy or platinum-doublet chemotherapy alone. The primary endpoint was overall survival. As of the six-year follow-up, the median overall survival was 25.6 months with nivolumab plus ipilimumab and chemotherapy, compared to 18.1 months with chemotherapy alone. These findings are detailed in the Bristol Myers Squibb press release issued January 18, 2024.