Abstract 169P
Background
A standard for extensive-stage small cell lung cancer (ES-SCLC) is induction therapy followed by thoracic radiation therapy (TRT). PARP inhibitors including olaparib have demonstrated radiosensitization in preclinical lung cancer models. We performed an investigator-initiated, multi-institutional, single-arm, open label phase I study on concurrent olaparib with TRT.
Methods
Patients with progression-free ES-SCLC after 4 to 6 cycles of platinum/etoposide ± atezolizumab, were treated with olaparib for 3 weeks with concurrent low-dose TRT (30 Gy/10 fractions) in weeks 2 and 3. Olaparib dose escalation using the continuous reassessment method started at 50 mg twice daily, escalating at 50 mg/dose level. Patients were permitted to continue atezolizumab maintenance after completion of TRT per standard of care. The primary objective was the safety and MTD of olaparib+TRT. Secondary objectives were in-field local recurrence rate and progression-free (PFS) and overall survival (OS).
Results
Between 10/2018 and 03/2022, 24 patients were treated (median follow-up: 11.4 months [range: 2 to 48 months]). Median age was 68 years (range: 49 to 79 years); ECOG status was 0–1 for 13 and 2 for 11 patients, respectively. All patients were treated with platinum/etoposide; 10 patients also received atezolizumab. All patients received 30 Gy/10 fractions TRT. The MTD of olaparib+TRT was 200 mg twice daily. There were 4 grade 3 (G3) dose-limiting adverse events (AEs), including pneumonitis, lung infection, esophagitis, and abdominal pain (each n = 1). Olaparib-related G2+ AEs included cough, dyspnea, dehydration, anorexia, dysgeusia, alopecia, and diarrhea (each n = 1). The most common G2+ TRT or olaparib+TRT-related AEs were esophagitis (n = 7), pneumonitis (n = 2), vomiting, dehydration, dyspepsia, maculo-papular rash, fever, and weight loss (each n = 1). There were no G4 or 5 AEs. No significant additional AEs were observed with atezolizumab maintenance. The 12-month cumulative incidence of local recurrence was 27%, median PFS was 3.6 months, and median OS was 17.7 months.
Conclusions
This is the first report on the safety and MTD of olaparib with concurrent low-dose TRT. The MTD of olaparib was identified as 200 mg twice daily.
Clinical trial identification
NCT03532880.
Legal entity responsible for the study
Memorial Sloan Kettering Cancer Center.
Funding
AstraZeneca.
Disclosure
A. Rimner: Financial Interests, Personal, Advisory Board: AstraZeneca, Merck; Non-Financial Interests, Institutional, Funding, This study was funded and supported by AstraZeneca: AstraZeneca; Non-Financial Interests, Institutional, Funding: Merck, Boehringer Ingelheim, Pfizer, Varian Medical Systems; Non-Financial Interests, Institutional, Research Grant: National Institute of Health; Other, Personal, Member of the Board of Directors: International Mesothelioma Interest Group; Other, Personal, Leadership Role, Vice President: International Thymic Malignancies Interest Group. B. Lok: Financial Interests, Institutional, Research Grant: Pfizer, AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Non-Financial Interests, Personal, Other: AstraZeneca. R.R. Kotecha: Financial Interests, Personal, Advisory Board: Accuray, Elekta AB, Novocure, Kazia Therapeutic, Castle Biosciences; Financial Interests, Personal, Invited Speaker: ViewRay, Elsevier, Brainlab; Financial Interests, Institutional, Research Grant: Medtronic, Blue Earth Diagnostics, Novocure, GT Medical Technologies, AstraZeneca, Exelixis, ViewRay, Brainlab, Cantex Pharmaceuticals, Kazia Therapeutics. A. Shepherd: Financial Interests, Personal, Stocks/Shares: Arcellx, Doximity. D. Gomez: Financial Interests, Institutional, Research Grant: Varian Medical Systems, AstraZeneca, Merck, Bristol Myers-Squibb; Financial Interests, Personal, Advisory Board: Grail, Olympus, Johnson & Johnson, Varian Medical Systems, Medtronic; Financial Interests, Personal, Invited Speaker: MedLearning Group. N. Shaverdian: Financial Interests, Institutional, Research Grant: Novartis. C.B. Simone: Financial Interests, Personal, Invited Speaker: Varian Medical Systems. H.A. Yu: Financial Interests, Personal and Institutional, Research Grant, Research Funding and consulting: AstraZeneca, Daiichi Sankyo, Cullinan, Black Diamond, Blueprint Med, Janssen; Financial Interests, Institutional, Research Grant: Novartis, Pfizer, ERASCA; Financial Interests, Personal, Advisory Board: Taiho, AbbVie. R. Daly: Financial Interests, Personal, Advisory Board: Varian Medical Systems; Financial Interests, Personal, Stocks/Shares: Roche; Financial Interests, Personal, Stocks/Shares, Immediate family member owns Eli Lilly equity: Eli Lilly. M.D. Offin: Financial Interests, Personal, Advisory Board: Novartis, Jazz, PharmaMar; Financial Interests, Personal, Invited Speaker: Targeted Oncology, OncLive, American Society for Radiation Oncology; Financial Interests, Personal, Other, Travel reimbursement: Bristol Myers-Squibb, Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant: LUNGevity Foundation; Non-Financial Interests, Personal, Advisory Role: Mesothelioma Applied Research Foundation. M. Ginsberg: Financial Interests, Personal, Invited Speaker: Ultimate Opinions in Medicine LLC. All other authors have declared no conflicts of interest.