Phase I Dose Escalation Trial Combining Olaparib and Thoracic Radiation Therapy in Extensive-Stage Small Cell Lung Cancer
Mené sur 24 patients atteints d'un cancer du poumon à petites cellules de stade étendu (âge médian : 68 ans ; durée médiane de suivi : 11,4 mois), cet essai de phase I détermine la dose maximale tolérée de l'olaparib en combinaison avec une radiothérapie thoracique puis évalue l'efficacité de cette combinaison du point de vue du taux de récidive locale, de la survie sans progression et de la survie globale
Purpose: Patients with extensive-stage small cell lung cancer (ES-SCLC) are commonly treated with induction systemic therapy and consolidative thoracic radiation therapy (TRT). PARP inhibitors have demonstrated radiosensitization in preclinical lung cancer models. We performed an investigator-initiated, multi-institutional, single-arm, open label phase I study of concurrent olaparib with TRT.
Patients and Methods: Patients without progression after induction platinum/etoposide +/- atezolizumab were treated with oral olaparib for 3 weeks and concurrent low-dose TRT (30 Gy/10 fractions) in weeks 2 and 3. Olaparib dose started at 50mg twice daily and escalated in 50mg/dose increments in cohorts of 3 patients each. Primary objectives were the safety and maximum tolerated dose (MTD) of olaparib + TRT. Secondary objectives included in-field local recurrence rate, progression-free survival (PFS), and overall survival (OS).
Results: Between 10/2018 and 03/2022, 24 patients with a median age of 68 years were treated (median follow-up: 11.4 months) with platinum/etoposide and 30 Gy/10 fractions TRT; 10 patients also received atezolizumab. The MTD of olaparib with TRT was 200mg twice daily. There were 3 grade 3 (G3) dose-limiting adverse events (AEs), including pneumonitis/pneumonia, esophagitis, and abdominal pain. The most common G2-3 treatment-related AEs were esophagitis (n=12) and pneumonitis/pneumonia (n=2). There were no G4 or 5 AEs. The 12-month cumulative incidence of local recurrence was 27%, median PFS and OS were 3.6 months and 17.7 months, respectively.
Conclusions: This study defined a MTD and recommended phase II dose of 200mg twice daily olaparib with concurrent low-dose TRT, and the combination appeared safe without unexpected toxicities.
Clinical Cancer Research , résumé, 2025