Poly (ADP-ribose) polymerase (PARP) inhibitor olaparib, combined with temozolomide, appeared safe and active in patients with relapsed small cell lung cancer (SCLC), according to the results of a single-arm phase 1/2 trial. The findings were published online August 15, 2019, in Cancer Discovery.1,2

The trial included a phase 1 dose-escalation portion followed by a dose-expansion protocol during phase 2. A total of 50 patients with previously treated SCLC were enrolled across the 2 phases of the trial. Patients received a median of 2 lines of prior therapy (range, 1–7), and the majority of patients (72%) had platinum-sensitive disease.

Four dose levels were evaluated during phase 1, and no grade 4/5 treatment-related events, serious adverse events, or dose-limiting toxicities were observed at any of dose levels evaluated. The recommended phase 2 dose (RP2D) ultimately selected was dose level 3, which was olaparib 200 mg orally twice daily and temozolomide 75 mg/m2 daily.

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Among the 48 patients evaluable for analysis, 20 (41.7%) achieved a response, all of which were partial responses. Among the 39 patients who received the RP2D, the overall response rate was 41.0%, median progression-free survival was 4.2 months (95% CI, 2.5-5.7), and median overall survival was 6.7 months (95% CI, 4.6-12.6).

During the phase 2 part of the trial, 2 grade 5 events occurred that were “possibly related” to the combination, including 1 case of pneumonia and 1 case of neutropenic sepsis.

“This combination showed significant clinical activity in patients with relapsed small cell lung cancer, and warrants investigation in a randomized study comparing olaparib plus temozolomide with the standard-of-care option,” said lead study author Anna Farago, MD, PhD, assistant professor of medicine at Harvard Medical School and Massachusetts General Hospital Cancer Center in Boston, Massachusetts, in a press release.

Disclosure: The original study was sponsored by AstraZeneca, the National Cancer Institute, the V Foundation, the National Institutes of Health, Uniting Against Lung Cancer, the Lung Cancer Research Foundation, the American Society of Clinical Oncology, the Deutsche Forschungsgemeinschaft, the Howard Hughes Medical Institute, the National Foundation for Cancer Research, and the Novartis-MGH Alliance.

Farago has a consulting/advisory role for PharmaMar, AbbVie, Loxo Oncology, Stemcentrx, Genentech/Roche, Bayer, AstraZeneca, Bristol-Myers Squibb, and Boehringer Ingelheim. Drapkin receives research funding from Novartis, AbbVie, Merck, and AstraZeneca.

References

  1. Farago AF, Yeap BY, Stanzione M, et al. Combination olaparib and temozolomide in relapsed small cell lung cancer [published online August 15, 2019]. Cancer Discov. doi: 10.1158/2159-8290.CD-19-0582
  2. American Association for Cancer Research. Combinatorial therapy shows early promise in patients with relapsed small cell lung cancer. Philadelphia, PA. Published August 15, 2019. Accessed August 18, 2019.