Atezolizumab Linked to Long-Term Survival in SCLC

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Findings from a long-term analysis of the phase 1/3 IMPower133 study (NCT02763579) found that long-term survival was more likely with atezolizumab (Tecentriq) vs placebo in patients with extensive-stage small cell lung cancer (ES-SCLC).¹

Long-term survivors were observed more frequently in the atezolizumab arm vs the placebo arm (34% vs 20%), and the odds for living longer than 18 months in the atezolizumab arm was double that of the placebo arm (OR, 2.1; P <.03).

Overall survival (OS) in the RNA-sequencing biomarker-evaluable population (n = 271) was 11.8 months (95% CI, 9.7-14.4) with atezolizumab plus carboplatin and etoposide (CP/ET). Comparatively, OS was 10.4 months (95% CI, 9.4-11.5) in the placebo plus CP/ET arm (HR, 0.80; 95% CI, 0.58-1.09; P =.016).

Further, atezolizumab appeared to have a treatment benefit in subgroups of patients with T-effector and B-cell gene signature expressions. In the low T-effector subgroup, the median OS with atezolizumab plus CP/ET was 9.9 months compared with 9.1 months with placebo plus CP/ET (HR, 0.75; 95% CI, 0.52-1.10). In the high T-effector subgroup, median OS was 15.9 months in the atezolizumab arm vs 10.7 months in the placebo arm (HR, 0.65; 95% CI, 0.43-0.97). In the low B-cell subgroup, the median OS was 9.9 months in the atezolizumab arm vs 9.0 months in the placebo arm (HR, 0.66; 95% CI, 0.45-0.97). In the high B-cell subgroup, median OS was 12.4 months in the atezolizumab arm vs 10.6 months in the placebo arm (HR, 0.75; 95% CI, 0.51-1.11).

“SCLC is a highly aggressive lung cancer associated with exceptionally poor prognosis and outcomes, in part attributable to the lack of targeted treatment options, which has kept the disease outside the realm of precision medicine. Genomic profiling of SCLC tumors has revealed a high mutation burden mostly characterized by inactivation of the tumor suppressor genes TP53 and RB1,” study authors wrote. “Overall, these findings showed that long-term survival is more likely with atezolizumab than placebo, and they confirmed the first-line treatment benefit of atezolizumab in combination with CP/ET in ES-SCLC.”

The study randomized 403 patients to receive either atezolizumab plus CP/ET (n = 201) or placebo plus CP/ET (n = 202). In the induction phase, patients received 4 21-day cycles of intravenous CP on day 1 and ET on days 1-3 plus atezolizumab or placebo on day 1. Patients then received maintenance therapy with the same doses of atezolizumab or placebo until disease progression or unacceptable toxicity were observed.

The primary end points of the study were OS and investigator-assessed progression-free survival per RECIST 1.1.

Several prognostic indicators were associated with long-term survival. These included an ECOG performance status of 0 (OR, 1.8; P =.03), low lactate dehydrogenase levels (OR, 1.8; P =.03), and a low number of metastatic sites (OR, 0.8; P =.03). Moreover, long-term survival in both the atezolizumab and placebo arms was associated with elevated expression of T-effector infiltration markers CD8A, IFNG, CXCL9, CXCL10, GZMA, GZMB, PRF1, and TBX21, as well as B-cell infiltration markers CD79A, CD79B, CD20, and VPREB3.

“The observation that there were more LTS in the atezolizumab plus CP/ET arm than in the placebo plus CP/ET arm confirms that a subset of patients with ES-SCLC who receive immunotherapy derive durable benefit, and further supports the treatment benefits of atezolizumab and the IMpower133 regimen,” study authors concluded.

REFERENCE:

1. Liu SV, Mok TSK, Nabet BY, et al. Clinical and molecular characterization of long-term survivors with extensive-stage small cell lung cancer treated with first-line atezolizumab plus carboplatin and etoposide. Lung Cancer. 2023;186:107418. doi:10.1016/j.lungcan.2023.107418