First‐Line Atezolizumab plus Chemotherapy in Extensive‐Stage Small‐Cell Lung Cancer

By L. Horn, A. Mansfield, A. Szczesna, L. Havel, M. Krzakowski, M. Hochmair, F. Huemer, G. Losonczy, M. Johnson, M. Nishio and 11 more. New England Journal of Medicine, 2018

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BACKGROUND Enhancing tumor‐specific T‐cell immunity by inhibiting programmed death ligand 1 (PD‐L1)–programmed death 1 (PD‐1) signaling has shown promise in the treatment of extensive‐stage small‐cell lung cancer. Combining checkpoint inhibition with cytotoxic chemotherapy may have a synergistic effect and improve efficacy. METHODS We conducted this double‐blind, placebo‐controlled, phase 3 trial to evaluate atezolizumab plus carboplatin and etoposide in patients with extensive‐stage small‐cell lung cancer who had not previously received treatment. Patients were randomly assigned in a 1:1 ratio to receive carboplatin and etoposide with either atezolizumab or placebo for four 21‐day cycles (induction phase), followed by a maintenance phase during which they received either atezolizumab or placebo (according to the previous random assignment) until they had unacceptable toxic effects, disease progression according to Response Evaluation Criteria in Solid Tumors, version 1.1, or no additional clinical benefit. The two primary end points were investigator‐assessed progression‐free survival and overall survival in the intention‐to‐treat population. RESULTS A total of 201 patients were randomly assigned to the atezolizumab group, and 202 patients to the placebo group. At a median follow‐up of 13.9 months, the median overall survival was 12.3 months in the atezolizumab group and 10.3 months in the placebo group (hazard ratio for death, 0.70; 95% confidence interval [CI], 0.54 to 0.91; P=0.007). The median progression‐free survival was 5.2 months and 4.3 months, respectively (hazard ratio for disease progression or death, 0.77; 95% CI, 0.62 to 0.96; P=0.02). The safety profile of atezolizumab plus carboplatin and etoposide was consistent with the previously reported safety profile of the individual agents, with no new findings observed. CONCLUSIONS The addition of atezolizumab to chemotherapy in the first‐line treatment of extensive‐stage small‐cell lung cancer resulted in significantly longer overall survival and progression‐free survival than chemotherapy alone. (Funded by F. Hoffmann–La Roche/Genentech; IMpower133 ClinicalTrials.gov number, NCT02763579.)

Subfields: Oncology

View Paper: https://www.semanticscholar.org/paper/b16ce24dd760ee75a6e14b0a29fba2ed8329f004

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Citations in the corpus

• Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133) (2021, methodology): “gov identifier: NCT02763579).(5) The trial was conducted in accordance with Good Clinical Practice and the Declaration of Helsinki.”
• Review of Indications of FDA-Approved Immune Checkpoint Inhibitors per NCCN Guidelines with the Level of Evidence (2020, background): “On 18 March 2019, atezolizumab, in combination with carboplatin and etoposide, received approval for first-line treatment in extensive-stage small-cell lung cancer, based on results from the Phase III IMpower133 study [83] (Category 1).”
• Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study (2020, background): “91) compared with placebo plus 4 cycles of etoposide and carboplatin.(9) In CASPIAN, the addition of durvalumab (anti–PD-L1) to 4 cycles of EP significantly improved the primary end point of OS compared with 6 cycles of EP (HR, 0.”