Patients With SLFN11-Expressing SCLC May Benefit From Immune Checkpoint Inhibitor Plus PARP Inhibitor

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Among patients with extensive-stage small cell lung cancer (SCLC) positive for expression of the Schlafen-11 gene (SLFN11), those who received maintenance treatment with the immune checkpoint inhibitor atezolizumab plus the PARP inhibitor talazoparib had significantly longer progression-free survival (4.2 months) than those who received atezolizumab alone (2.8 months). These results from the phase II S1929 trial, conducted by the SWOG Cancer Research Network, were reported by Abdel Karim et al at the 2023 ASCO Annual Meeting (Abstract 8504).

The work was led by and presented by Nagla Abdel Karim, MD, a SWOG investigator who directs the Early Therapeutics Program at the Inova Schar Cancer Institute and the University of Virginia.

“The results of S1929 demonstrate improvement in progression-free survival in patients with SLFN11-expressing SCLC,” Dr. Abdel Karim said. “This is a groundbreaking milestone in building future studies for SCLC towards a personalized approach to therapy. Progression-free survival is of great clinical significance, especially in this aggressive disease.”

More About S1929

The S1929 study randomly assigned 106 patients who received front-line chemotherapy with atezolizumab and whose tumors tested positive for SLFN11 expression to receive either maintenance atezolizumab or atezolizumab plus talazoparib; all randomized patients were included in the analysis. Progression-free survival was the primary endpoint in the trial.

Patients in the atezolizumab-plus-talazoparib arm had a risk of disease progression or death that was reduced by 30% (progression-free survival hazard ratio [80% confidence interval] = 0.70 [0.52–0.94], P = .056) compared to patients on the atezolizumab-only arm.

Secondary endpoints included overall survival. Median overall survival was similar between the two arms: 9.4 months in the atezolizumab-plus-talazoparib arm vs 8.5 months in the atezolizumab-only arm.

Patients receiving atezolizumab plus talazoparib experienced significantly more hematologic adverse events than those receiving only atezolizumab—50% vs 4%—although this increased rate of hematologic toxicity was expected. Nonhematologic adverse event rates were similar between the two arms: 15% vs 13%, respectively.

The authors noted that the S1929 study results also demonstrated, for the first time, the feasibility of conducting biomarker-selected trials in patients with SCLC, which could pave the way for future trials that evaluate new therapies for the disease in selected patient populations.

“Managing SCLC based on predictive biomarkers is now seen as a possibility that will change clinical practice,” Dr. Abdel Karim said.

Disclosure: Study S1929 was funded by the National Institutes of Health (NIH)/National Cancer Institute (NCI), and in part through a grant from the NIH/NCI’s Biomarker, Imaging, & QOL Studies Funding Program. Additional support was provided by Genentech, Pfizer, The University of Texas MD Anderson Cancer Center Lung Cancer Moonshot Program, and the Andrew Sabin Family Fellowship. For full disclosures of the study authors, visit

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