Abstract 1326P
Background
The aim of this study is to assess whether combined anti-programmed-cell-death-1 (anti-PD-1) therapy and stereotactic ablative radiotherapy (SABR) improves outcomes in patients with metastatic non-small cell lung cancer (NSCLC) and melanoma in oligoprogression to anti-PD-1.
Methods
This prospective study from 4 hospitals in Spain included patients with metastatic NSCLC or melanoma who were in confirmed progression to anti-PD-1 but maintained the same line due to clinical benefit. All patients were referred for palliative SABR. Prior to SABR, we selected 1-5 measurable lesions for treatment and, if applicable, up to 2 non-target lesions outside of the planned radiation field to evaluate the abscopal response (AR). SABR was administered in 5 non-consecutive fractions (3 in case of dose-limiting constraints). Anti-PD-1 was administered concurrently and continued until progression and loss of clinical benefit or in the event of limiting toxicities. Response was assessed by RECIST 1.1 The primary endpoint was the objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), local control (LC), acute toxicity (CTCAE v.4.3), time to new systemic treatment and AR.
Results
We enrolled 61 patients from September 2017 to August 2020. Of those, 50 fulfilled the study criteria for follow-up and could be included for analysis. These had a median age of 64 (range 39-87) and were in progression to nivolumab (n=23) or pembrolizumab (n =27). With a median follow-up of 33 months (range 5-45), ORR was 42% (15 complete and 6 partial responses). Median PFS was 14.2 months (95% CI, 6.9 – 29) and median OS was 37.4 months (95% CI, 22.9 – not reached). LC was 84%. Toxicity rates were similar before and after SABR. Patients maintained the same anti-PD-1 for a median of 11 months post-SABR (range 1–45). AR was measurable in 40/50 patients. Of these, 26 (65%) presented AR at 2 months.
Conclusions
In patients with stage IV NSCLC and melanoma which become unresponsive to anti-PD-1, SABR to oligoprogressive sites can unleash immune-related systemic effects that improve disease control and delay further progression, allowing for the continuation of anti-PD-1.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
D. Rodriguez: Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb; Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Institutional, Advisory Board: Merck Sharp & Dohme; Financial Interests, Institutional, Invited Speaker: F. Hoffmann-La Roche; Financial Interests, Institutional, Advisory Board: F. Hoffmann-La Roche; Financial Interests, Institutional, Invited Speaker: Pierre Fabre; Financial Interests, Institutional, Advisory Board: Pierre Fabre; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Advisory Board: Lilly; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Advisory Board: AstraZeneca. All other authors have declared no conflicts of interest.