Randomized phase II trial investigating whether atezolizumab after chemoradiotherapy (CRT) prolongs survival in limited stage (LS) small cell lung cancer (SCLC).

LBA8005 Background: A majority of patients with LS SCLC relapse after potentially curative CRT and better treatment is needed. Immunotherapy prolongs survival in extensive stage SCLC and after CRT in non-small cell lung cancer. We investigated whether atezolizumab (“atezo”) after CRT prolongs survival in LS SCLC. Methods: Patients with PS 0-2 and non-progression (PD) after platinum/etoposide chemotherapy and concurrent twice-daily thoracic radiotherapy (TRT) of 45 Gy/30 or 60 Gy/40 fractions were randomized 1:1 to observation or atezo 1200 mg Q3W for 1 year, until PD or unacceptable toxicity. Atezo commenced 3-7 weeks after CRT. Randomization was stratified by performance status (PS) (0-1 vs. 2), CRT-response (stable disease [SD] vs. complete/partial response [CR/PR]) and TRT-dose (45 Gy vs. 60 Gy). CRT-responders were offered prophylactic cranial irradiation (PCI) of 25-30 Gy. PCI was allowed after start of atezo. Primary endpoint: Overall survival (OS). Secondary endpoints: Response rate (ORR), progression-free survival (PFS) and toxicity. To detect an increase in 2-year survival from 53% to 66% with a 1-sided a=0.1 and b=0.2, 75 patients were required in each group. Results: From July 2018-April 2022, 216 patients were included at 37 European hospitals. 170 (78.7%) were randomized (atezo: n=85, observation: n=85). Median age was 66 years, 46% were women, 92% had PS 0-1 and 82% stage III disease. ORR to CRT was similar in the atezo (95%) and observation (94%) groups. 67% in both groups received PCI. Median number of atezo-cycles was 8 (range 0-18), 2% of patients received 0 cycles and 34% completed 1 year of treatment. Atezo was discontinued due to PD (n=18), pneumonitis (n=8), endocrinopathy (n=3), neurotoxicity (n=2), myositis (n=2), other toxicity (n=9), patients’ wish (n=5), death from other disease (n=2) and other (n=5). Median time until discontinuation of atezo due to toxicity was 2.8 (range 0.1-12.1) months. After randomization (i.e. post CRT), G3-4 toxicity was reported for 34% in the atezo group (dyspnea [n=6], fatigue [n=5], endocrinopathies [n=5], cardiac disorder [n=4], other [n=36]), and 20% in the control group (anorexia [n=6], neuropathy [n=5], dyspnea [n=4], and other [n=24]). G3-4 pneumonitis occurred in 4 patients, 2 in each group. There were 3 treatment-related deaths (neurotoxicity, pneumonitis and pneumonia), all in the atezo group. After 99 events and median follow-up 45.1 months (95% CI 40.7-47.3), median OS from randomization was 43.3 months (95% CI 25.1-51.2) in the atezo and 38.8 months (95% CI 25.8-NR) in the observation group (HR 1.14, 95% CI 0.76-1.72; p=0.5). Median PFS was 21.1 months (95% CI 9.5-43.4) in the atezo and 15.9 (95% CI 10.6-23.2) in the observation group (HR 0.88, 95% CI 0.60-1.28, p=0.5). Conclusion: Atezolizumab therapy after CRT did not improve progression free or overall survival in patients with LS SCLC. Clinical trial information: NCT03540420 .