Novel Combinations of Immunotherapies or DNA Damage Repair Inhibitors in Platinum-Refractory Extensive-Stage Small Cell Lung Cancer: The Phase II BALTIC Study.
| Autor: | Reinmuth N; Department of Thoracic Oncology, Asklepios Lung Clinic Munich-Gauting, Gauting, Germany.; German Center of Lung Research, LMU Munich, Munich, Germany., Juan-Vidal O; Department of Medical Oncology, La Fe University Hospital, Valencia, Spain., Kowalski D; Department of Lung Cancer and Thoracic Tumours, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland., Bryl M; Oncology Department, E.J. Zeyland Wielkopolska Center of Pulmonology and Thoracic Surgery, Poznan, Poland., Kryzhanivska A; Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine., Vicente D; Hospital Universitario Virgen Macarena, Seville, Spain., Horváth Z; Bacs-Kiskun County Teaching Hospital, Kecskemét, Hungary., Gálffy G; Pulmonology Hospital Törökbálint, Törökbálint, Hungary., Csánky E; Department of Pulmonology, Semmelweis Hospital, Miskolc, Hungary., Pápai Székely Z; St George Hospital of Fejér County, Szekesfehervar, Hungary., Vynnychenko I; Sumy State University, Sumy, Ukraine., Armstrong J; AstraZeneca, Cambridge, United Kingdom., Dalvi T; AstraZeneca, Gaithersburg, Maryland., Xie M; AstraZeneca, Waltham, Massachusetts., Iyer S; AstraZeneca, Waltham, Massachusetts., Shrestha Y; AstraZeneca, Gaithersburg, Maryland., Jiang H; AstraZeneca, Gaithersburg, Maryland., Bondarenko I; Dnipropetrovsk State Medical Academy, Dnipropetrovsk, Ukraine. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Sep 13; Vol. 30 (18), pp. 4055-4067. |
| DOI: | 10.1158/1078-0432.CCR-24-0013 |
| Abstrakt: | Purpose: The phase II, multiarm, signal-searching BALTIC study (NCT02937818) assessed novel treatment combinations for platinum-refractory/resistant extensive-stage small cell lung cancer (ES-SCLC). Patients and Methods: Patients with ES-SCLC with progressive disease during or within 90 days of completing first-line platinum-based chemotherapy received one of three regimens: durvalumab plus tremelimumab followed by durvalumab monotherapy (arm A), adavosertib plus carboplatin (arm B), or ceralasertib plus olaparib (arm C). The primary endpoint was the objective response rate. Prespecified exploratory biomarker analyses were conducted in arms A and C. Results: In arm A (n = 41), arm B (n = 10), and arm C (n = 21), the confirmed objective response rates were 7.3%, 0%, and 4.8%, respectively. Safety profiles in all arms were consistent with those of the individual drugs. In arm A, patients with PD-L1 expression (tumor cells or immune cells) ≥1% seemed to have a greater likelihood of achieving disease control with durvalumab plus tremelimumab than those with PD-L1 (tumor cells and immune cells) <1%, and lower baseline ctDNA and reduction in the on-treatment ctDNA level were both associated with longer overall survival. Among patients treated with ceralasertib plus olaparib in arm C, specific immune response-relevant circulating chemokines and cytokines were identified as early biomarkers of survival and pharmacodynamic biomarkers. Conclusions: In BALTIC, all combination regimens demonstrated tolerable safety profiles, but antitumor activity was limited in refractory/resistant ES-SCLC. Among patients treated with durvalumab plus tremelimumab, an association of on-treatment reduction in ctDNA with longer overall survival suggests the potential use of ctDNA as a surrogate of treatment response, warranting further investigation. (©2024 The Authors; Published by the American Association for Cancer Research.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|