1221P - Stereotactic ablative radiotherapy in combination with nivolumab for early stage operable non-small cell lung cancer: A phase II study

Background

Stereotactic ablative radiotherapy (SABR) is routinely used in patients with early-stage non–small cell lung cancer (NSCLC) who are not candidates for surgery. Despite excellent local tumor control, it is associated with a high rate of regional and distant recurrences. Combining SABR with PD-1 inhibitors have shown encouraging results for patients with curative intent, but how it affects the tumor microenvironment and pathologic response remains unclear.

Methods

This is a phase II, open-label, single-arm study aimed to evaluate the efficacy and safety of neoadjuvant nivolumab combined with SABR in patients with NSCLC measuring up to 4 cm without positive lymph nodes. Patients were required to be eligible for surgery. Nivolumab at 360 mg every 21 days was given for three doses, combined with SABR, which was initiated concomitantly with the first cycle. Surgical resection was performed after 10 weeks from the last dose of radiation. The primary endpoint was pathological complete response (pCR) rate at surgery. Secondary endpoints included major pathological response (MPR) rate, safety, event-free survival (EFS) and overall survival (OS) at 12 months as well as a comprehensive biomarker analysis.

Results

25 patients were enrolled between Nov 2019, and Feb 2022. Mean age was 68 years and 68% were female. Mean tumor size at baseline was 2.47 cm. 24 patients fully completed the experimental therapy and proceeded with surgery. The primary endpoint of pCR was achieved by 19/24 patients analysis (79.2%; 95% CI, 57%-92%, p-value 0.0875, in the per protocol analysis). MPR was observed in 20 cases (83.3%; 95% CI, 61.8%-94%). Four patients have not achieved an MPR, with one of them with 100% of residual viable tumor. No patient relapsed to date, with 12-month EFS and OS of 84%. The sole patient who was not operated died of relapsed alcoholic hepatitis during neoadjuvant treatment, unrelated to experimental therapy. Two patients died from surgical complications.

Conclusions

The neoadjuvant combination of three doses of nivolumab and SABR produced a high pCR rate without major adverse events. Further research is warranted to evaluate this treatment modality in inoperable patients and whether surgery could be safely omitted.

Clinical trial identification

NCT04271384.

Editorial acknowledgement

Legal entity responsible for the study

Hospital Israelita Albert Einstein.

Funding

Bristol Myers Squibb.

Disclosure

G. Schvartsman: Financial Interests, Personal, Research Funding: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: MSD, Sanofi, Amgen, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Adium, Janssen, Roche. All other authors have declared no conflicts of interest.