There is a lack of clinical evidence supporting the use of olaparib specifically for BRCA2 somatic-positive small cell lung cancer (SCLC). While early-phase trials show a biologic rationale for PARP inhibition and modest activity in unselected SCLC, no published data report outcomes specifically for BRCA2-mutated patients. The SUKSES-B trial included patients with BRCA2 mutations but reported only overall results for the homologous recombination-mutant cohort, showing limited single-agent act...
The latest National Comprehensive Cancer Network (NCCN) small cell lung cancer (SCLC) guidelines do not provide any recommendations for the use of olaparib or other poly(ADP-ribose) polymerase (PARP) inhibitors based on breast cancer gene 1 or 2 (BRCA1/2) germline or somatic mutations in SCLC. Available guideline summaries describe standard systemic therapy approaches (platinum-etoposide-based regimens, immunotherapy, lurbinectedin, topotecan, etc.) and do not list PARP inhibitors as recommended or biomarker-directed options for SCLC. [1]
Published reviews describe a biologic rationale for PARP inhibition in SCLC), including high PARP1 expression and increased DNA damage response pathway activity, along with preclinical studies showing greater sensitivity to olaparib compared with other lung cancer subtypes; however, these findings are not specific to BRCA2-mutated disease. Early clinical trials of PARP inhibitors in SCLC have generally shown limited activity as monotherapy, in...
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What data support the use of olaparib for the treatment of BRCA2 somatic positive small cell lung cancer?
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[1] National Comprehensive Cancer Network (NCCN). Small Cell Lung Cancer. Version 2.2026. Updated September 16, 2025. https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf
[2] Barayan R, Ran X, Lok BH. PARP inhibitors for small cell lung cancer and their potential for integration into current treatment approaches. J Thorac Dis. 2020;12(10):6240-6252. doi:10.21037/jtd.2020.03.89
[3] Knelson EH, Patel SA, Sands JM. PARP Inhibitors in Small-Cell Lung Cancer: Rational Combinations to Improve Responses. Cancers (Basel). 2021;13(4):727. Published 2021 Feb 10. doi:10.3390/cancers13040727
[4] Clinicaltrials.gov. Olaparib Monotherapy in Relapsed Small Cell Lung Cancer Patients With HR Pathway Gene Mutations Not Limited to BRCA 1/2 Mutations, ATM Deficiency or MRE11A Mutations (SUKSES-B; NCT03009682). Last updated February 18th, 2021. Accessed February 13th, 2026. https://clinicaltrials.gov/study/NCT03009682
[5] Park S, Kim YJ, Min YJ, et al. Biomarker-driven phase 2 umbrella trial: Clinical efficacy of olaparib monotherapy and combination with ceralasertib (AZD6738) in small cell lung cancer. Cancer. 2024;130(4):541-552. doi:10.1002/cncr.35059
[6] Woll P, Gaunt P, Danson S, et al. Olaparib as maintenance treatment in patients with chemosensitive small cell lung cancer (STOMP): A randomised, double-blind, placebo-controlled phase II trial. Lung Cancer. 2022;171:26-33. doi:10.1016/j.lungcan.2022.07.007
[7] Krebs MG, Delord JP, Jeffry Evans TR, et al. Olaparib and durvalumab in patients with relapsed small cell lung cancer (MEDIOLA): An open-label, multicenter, phase 1/2, basket study. Lung Cancer. 2023;180:107216. doi:10.1016/j.lungcan.2023.107216
[8] Farago AF, Yeap BY, Stanzione M, et al. Combination Olaparib and Temozolomide in Relapsed Small-Cell Lung Cancer. Cancer Discov. 2019;9(10):1372-1387. doi:10.1158/2159-8290.CD-19-0582