CHICAGO — Therapy with nivolumab plus chemotherapy improved PFS compared with chemotherapy alone among patients with newly diagnosed advanced non-small cell lung cancer and PD-L1 expression less than 1%, according to phase 3 results from the CheckMate 227 study presented at ASCO Annual Meeting.
“Identifying effective treatment for patients without known predictive biomarkers remains an unmet need,” Hossein Borghaei, DO, MS, medical oncologist at Fox Chase Cancer Center, said during his presentation. “Results are encouraging in this analysis, which included only patients with less than 1% PD-L1 expression.”
Platinum chemotherapy has long been the standard for patients with newly diagnosed NSCLC. PD-1 immunotherapies have emerged as a new treatment option for this patient population; however, only a small percentage of patients with NSCLC respond.
Recent studies demonstrated the addition of anti-PD-L1 therapy to chemotherapy may improve outcomes compared with chemotherapy among patients with nonsquamous NSCLC.
As HemOnc Today previously reported, the open-label multipart CheckMate 227 study met its coprimary endpoint of prolonged PFS with nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) compared with chemotherapy among patients with high tumor mutational burden (10 mutations per megabase or greater).
Part 1 of CheckMate-227 included 1,739 patients with chemotherapy-naive, histologically confirmed stage IV or recurrent NSCLC, ECOG performance status of 0 or 1, and no known sensitizing EGFR or ALK mutations.
In part 1a, researchers assigned patients with PD-L1 expression of 1% or higher (n = 1,189) to one of three regimens: nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks (n = 396), nivolumab monotherapy dosed at 240 mg every 2 weeks (n = 396), or histology-based doublet chemotherapy (n = 397).
In part 1b, investigators assigned patients with PD-L1 expression less than 1% (n = 550) to one of three regimens: nivolumab plus ipilimumab (n = 187; median age, 63 years), nivolumab 360 mg every 3 weeks plus histology-based chemotherapy (n = 177; median age, 64 years), or chemotherapy alone (n = 186; ; median age, 64 years).
Treatment continued up to 2 years or until disease progression or unacceptable toxicity.
Secondary endpoints included PFS for nivolumab plus chemotherapy compared with chemotherapy alone among patients with less than 1% tumor PD-L1 expression.
A descriptive analysis presented at ASCO indicated 1-year PFS among patients with less than 1% PD-L1 expression — regardless of disease histology — who received nivolumab plus chemotherapy was 26% compared with 14% among patients who received chemotherapy alone.
The median PFS was 5.6 months in the nivolumab-chemotherapy group and 4.7 months in the chemotherapy group, for an HR of 0.74 (95% CI, 0.58-0.94).
“The addition of chemotherapy to nivolumab led to an increase in response rate of about 37% vs. 23% with chemotherapy alone; however, these responses did not appear to be durable,” Borghaei said.
The proportion of patients who remained in response at 1 year reached only 28% in the nivolumab-chemotherapy group and 24% in the chemotherapy-alone group.
Subgroup analysis suggested the addition of nivolumab to chemotherapy benefitted most patients, but especially those with nonsquamous disease (HR = 0.68) relative to squamous disease (HR = 0.92).
Among patients with high tumor mutational burden of 10 mutations per megabase or greater and less than 1% PD-L1 expression, those assigned nivolumab plus chemotherapy achieved longer median PFS than those assigned chemotherapy (6.2 months vs. 5.3 months; HR = 0.56; 95% CI, 0.35-0.91). Patients with lower tumor mutational burden of less than 10 mutations per megabase and less than 1% tumor PD-L1 expression who received nivolumab-chemotherapy or chemotherapy alone had the same median PFS (4.7 months for both; HR = 0.87; 95% CI, 0.57-1.33).
The ORR for patients with high tumor mutational burden who received nivolumab-chemotherapy was 60.5% compared with 20.8% of patients who received just chemotherapy.
The ORR for patients with low tumor mutational burden who received nivolumab-chemotherapy was 27.8% compared with 22% of patients who received just chemotherapy.
Patients with high tumor mutational burden and less than 1% tumor PD-L1 expression had the longest PFS with nivolumab-ipilimumab (7.7 months; HR = 0.48 vs. chemotherapy; 95% CI, 0.27-0.85) compared with nivolumab-chemotherapy (6.2 months; HR = 0.56 vs. chemotherapy; 95% CI, 0.35-0.91) and chemotherapy alone (5.3 months).
Patients with lower tumor mutational burden and less than 1% tumor PD-L1 expression only had median PFS of 3.1 months (HR = 1.17 vs. chemotherapy; 95% CI, 0.76-1.81) with nivolumab-ipilimumab.
Researchers observed treatment-related deaths across Part 1 (encompassing patients with PD-L1 expression of 1% or higher enrolled in Part 1a and patients with PD-L1 expression less than 1% enrolled in Part 1b) among four patients who received nivolumab-chemotherapy, seven who received nivolumab-ipilimumab group and six in the chemotherapy group.
More grade 3 to 4 adverse events occurred among patients who received nivolumab-chemotherapy (n = 52) compared with nivolumab-ipilimumab (n = 25) or chemotherapy alone (n = 35).
“Treatment-related adverse events in the [chemotherapy] arm were consistent with other reports,” Borghaei said.
The combination of nivolumab and chemotherapy appeared well tolerated among patients with more durable response rate.
“Tumor mutational burden may be clinically relevant to select patients for immuno-oncology plus chemotherapy in addition to immuno-oncology plus immuno-oncology [treatment].” – by Melinda Stevens
Borghaei H, et al. Abstract 9001. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: Borghaei reports consultant roles with AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, Merck and Novartis; research funding from Bristol-Myers Squibb, Celgene, Eli Lilly, Merck and Millennium; and travel accommodations or expenses from AstraZeneca, Celgene, Eli Lilly, Genentech, Merck and Novartis. Please see the abstract for all other authors’ relevant financial disclosures.