As reported in the Journal of Clinical Oncology by Stephen V. Liu, MD, and colleagues, an updated overall survival analysis in the phase I/III IMpower133 trial showed continued benefit with the addition of atezolizumab to carboplatin/etoposide as first-line treatment in patients with extensive-stage small cell lung cancer (SCLC). A benefit with atezolizumab was observed irrespective of PD-L1 or blood-based tumor mutational burden status.
The primary analysis of the trial showed improved progression-free and overall survival with the addition of atezolizumab, and supported the March 2019 approval of the agent in combination with carboplatin/etoposide in first-line treatment of adult patients with extensive-stage SCLC. At primary analysis, with a median follow-up of 13.9 months, median overall survival was 12.3 months in the atezolizumab group vs 10.3 months in the carboplatin/etoposide group (hazard ratio [HR] = 0.70, P = .007) and median progression-free survival was 5.2 months vs 4.3 months (HR = 0.77, P = .02).
“Adding atezolizumab to carboplatin/etoposide as first-line treatment for extensive-stage SCLC continued to demonstrate improved overall survival and a tolerable safety profile at the updated analysis, confirming the regimen as a new standard of care. Exploratory analyses demonstrated treatment benefit independent of biomarker status.”— Stephen V. Liu, MD, and colleagues
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Study Details
In the double-blind trial, 403 patients were randomly assigned to receive atezolizumab plus carboplatin/etoposide (n = 201) or placebo plus carboplatin/etoposide (control group, n = 202). Treatment consisted of four 21-day cycles of carboplatin (AUC = 5 mg per mL/min on day 1) plus etoposide (100 mg/m2 on days 1–3) plus either atezolizumab (1,200 mg on day 1) or placebo, with maintenance atezolizumab or placebo continued until disease progression, unacceptable toxicity, or loss of clinical benefit. PD-L1 testing was not required for enrollment. The two primary endpoints were investigator-assessed progression-free survival and overall survival.
Key Findings
At data cutoff for the preplanned updated analysis (January 2019), follow-up had continued for an additional 9 months. Median follow-up was 23.1 months in the atezolizumab group and 22.6 months in the control group.
At the updated overall survival analysis, median overall survival was 12.3 months (95% confidence interval [CI] = 10.8–15.8 months) in the atezolizumab group vs 10.3 months (95% CI = 9.3–11.3 months) in the control group (HR = 0.76, 95% CI = 0.60–0.95, descriptive P = .0154), with 12- and 18-month rates of 51.9% vs 39.0% and 34.0% vs 21.0%.
At updated analysis, median-progression-free survival was 5.2 months vs 4.3 months (HR = 0.77, 95% CI = 0.63–0.95). Updated response analysis showed confirmed objective response rates of 60.2% vs 64.4% (descriptive P = .3839). Median duration of response was 4.2 months vs 3.9 months (HR = 0.67, 95% CI = 0.51–0.88).
Among 137 patients with available PD-L1 status, median overall survival among those with PD-L1 expression on tumor cells or tumor-infiltrating immune cells < 1%, ≥ 1%, and ≥ 5% was 10.2 vs 8.3 months (HR = 0.51, 95% CI = 0.30–0.89), 9.7 vs 10.6 months (HR = 0.87, 95% CI = 0.51–1.49), and 21.6 vs 9.2 months (HR = 0.60, 95% CI = 0.25–1.46).
Among 346 patients with available blood-based tumor mutational burden status, hazard ratios were 0.73 (95% CI = 0.49–1.08) and 0.73 (95% CI = 0.53–1.00) for blood-based tumor mutational burden scores < 10 and ≥ 10, and 0.79 (95% CI = 0.60–1.04) and 0.58 (95% CI = 0.34–0.99) for scores < 16 and ≥ 16.
Adverse events were consistent with those reported in the primary analysis. Immune-related adverse events that required systemic corticosteroid treatment occurred in 20.2% vs 5.6% of patients. The most common immune-related adverse events were rash (20.2% vs 10.7%), hypothyroidism (12.6% vs 0.5%), hepatitis (7.6% vs 4.6%), and infusion-related reactions (5.6% vs 5.1%); immune-related pneumonitis occurred in 2.5% vs 2.6% of patients.
The investigators concluded, “Adding atezolizumab to carboplatin/etoposide as first-line treatment for extensive-stage SCLC continued to demonstrate improved overall survival and a tolerable safety profile at the updated analysis, confirming the regimen as a new standard of care. Exploratory analyses demonstrated treatment benefit independent of biomarker status.”
Dr. Liu, of Georgetown Lombardi Comprehensive Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by F. Hoffmann-La Roche Ltd/Genentech, Inc, a member of the Roche Group. For full disclosures of the study authors, visit ascopubs.org.
