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J. Thorac. Oncol., Available online 29 June 2023 | https://doi.org/10.1016/j.jtho.2023.06.013 Durvalumab in Combination with Olaparib Versus Durvalumab Alone as Maintenance Therapy in Metastatic NSCLC: The Phase 2 ORION Study

Myung-Ju Ahn¹, Igor Bondarenko ², Ewa Kalinka ³, Byoung Chul Cho ⁴, Shunichi Sugawara ⁵, Gabriella Gálffy ⁶, Byoung Yong Shim ⁷, Nikolay Kislov⁸, Rajnish Nagarkar ⁹, Ingel Demedts ¹⁰, Steven J M Gans ¹¹, Dolores Mendoza Oliva ¹², Ross Stewart ¹³, Zhongwu Lai ¹⁴, Helen Mann¹³, Xiaojin Shi ¹⁵, Maen Hussein ¹⁶

¹Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
²Dnipropetrovsk Medical Academy, Dnipro, Ukraine.
³Polish Mother's Memorial Hospital - Research Institute, Lodz, Poland.
⁴Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
⁵Sendai Kousei Hospital, Sendai, Japan.
⁶Pest County Pulmonology Hospital, Törökbálint, Hungary.
⁷Department of Medical Oncology, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Republic of Korea.
⁸State Budget Institution of Health Yaroslavl Region "Regional Clinical Oncology Hospital", Yaroslavl, Russia.
⁹HCG Manavata Cancer Centre - Nashik, Nashik, Maharashtra, India.
¹⁰AZ Delta, Roeselare, Belgium.
¹¹Ziekenhuis St Jansdal, Harderwijk, Holland, The Netherlands.
¹²Centro Potosino de Investigación Médica, San Luis Potosí, Mexico.
¹³AstraZeneca, Cambridge, UK.
¹⁴AstraZeneca, Waltham, MA, USA.
¹⁵AstraZeneca, Gaithersburg, MD, USA.
¹⁶Florida Cancer Specialists - Sarah Cannon Research Institute, Leesburg, FL, USA.

^*Corresponding author: Prof. Myung-Ju Ahn

Abstract

Introduction: Increased DNA damage triggered through poly (ADP-ribose) polymerase inhibition may modify tumor immunogenicity, sensitizing tumors to immunotherapy. ORION (NCT03775486) evaluated the combination of olaparib with durvalumab as maintenance therapy in patients with metastatic NSCLC.

Methods: ORION is a Phase 2, randomized, multicenter, double-blind, international study. Patients with metastatic NSCLC (without activating EGFR/ALK aberrations) and ECOG PS 0/1 were enrolled to receive initial therapy with durvalumab (1500 mg IV; Q3W) plus platinum-based chemotherapy for four cycles. Patients without disease progression were then randomized (1:1) to maintenance durvalumab (1500 mg; Q4W) plus either olaparib (300 mg orally) or placebo (both twice daily); randomization was stratified by objective response during initial therapy and tumor histology. The primary endpoint was investigator-assessed PFS (RECIST v1.1).

Results: Between January 2019 and February 2020, 269/401 patients who received initial therapy were randomized. As of January 11, 2021 (median follow-up: 9.6 months), median PFS was 7.2 months (95% CI: 5.3-7.9) with durvalumab-plus-olaparib versus 5.3 months (3.7-5.8) with durvalumab-plus-placebo (HR = 0.76; 95% CI: 0.57-1.02; p = 0.074). Safety findings were consistent with the known profiles of durvalumab and olaparib. Anemia was the most common AE with durvalumab-plus-olaparib (26.1%; vs. 8.2% with durvalumab-plus-placebo). The incidence of grade 3/4 AEs (34.3% vs. 17.9%) and AEs leading to treatment discontinuation (10.4% vs. 4.5%) was numerically higher with durvalumab-plus-olaparib versus durvalumab-plus-placebo.

Conclusions: Maintenance therapy with durvalumab in combination with olaparib was not associated with a statistically significant improvement in PFS versus durvalumab alone, although numerical improvement was observed.

논문정보

형식Research article
게재일2023년 06월 (BRIC 등록일 2023-08-07)
연구진국내(교신)+국외 연구진
분야 의약학 > 종양의학

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