Response and outcomes after anti-CTLA4 versus anti-PD1 combined with stereotactic body radiation therapy for metastatic non-small cell lung cancer: retrospective analysis of two single-institution prospective trials

Abstract

Background: This study compared response rates and outcomes of combined radiotherapy and immunotherapy (iRT) based on the type of checkpoint inhibitor (anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) vs antiprogrammed death-1 (PD1)) for metastatic non-small cell lung cancer (mNSCLC).

Methods: We retrospectively reviewed two prospective trials of radiation combined with anti-CTLA4 or anti-PD1 for patients with mNSCLC. Patients undergoing non-salvage stereotactic body radiation therapy (SBRT) to lung sites were selected from both trials and grouped by the immunotherapeutic compound received. Endpoints included in-field and out-of-field response rates, and overall response rate (complete or partial response) (all by response evaluation criteria in solid tumors). Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method.

Results: Median follow-up times for the 33 patients (n=17 SBRT+anti-CTLA4, n=16 SBRT+anti-PD1) were 19.6 and 19.9 months. Response rates for out-of-field lesions were similar between anti-PD1 (37%) and anti-CTLA4 (24%) (p=0.054). However, global response rates for all lesions were 24% anti-CTLA4 vs 56% anti-PD1 (p=0.194). The PFS was 76% for anti-CTLA4 vs 94% anti-PD1 at 3 months, 52% vs 87% at 6 months, 31% vs 80% at 12 months, and 23% vs 63% at 18 months (p=0.02). Respective OS values were 76% vs 87% at 6 months, 47% vs 80% at 12 months, and 39% vs 66% at 18 months (p=0.08).

Conclusions: Both anti-CTLA4 and anti-PD1 agents prompt a similar degree of in-field and out-of-field responses after iRT, although the global response rate and PFS were statistically higher in the anti-PD1 cohort. Further dedicated study and biological mechanistic assessment is required.

Trial registration numbers: NCT02239900 and NCT02444741.

Keywords: immunotherapy; radiotherapy.

Conflict of interest statement

Competing interests: JW has received grants from Bristol-Myers Squibb, Merck, Varian, and OncoResponse; he also is a cofounder of Healios, MolecularMatch, and OncoResponse (with ownership interest); he is on the scientific advisor board of Mavu, Reflexion Medical and Checkmate Pharmaceuticals, and receives laboratory research support from Varian, Incyte, Calithera, and Checkmate Pharmaceuticals.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Flowchart of patient selection for this analysis. CTLA4, cytotoxic T-lymphocyte-associated protein 4; F/U, follow-up; NSCLC, non-small cell lung cancer; RT, radiation therapy; SBRT, stereotactic body radiation therapy.

Figure 2

Waterfall and distribution plots of out-of-field responses. Values were derived from changes in the sum of the longest diameter of the out-of-field lesions, assessed according to response evaluation criteria in solid tumors guidelines: overall response rate (ie, PR/complete response) and disease control rate (ie, any response other than PD). CTLA4, cytotoxic T-lymphocyte-associated protein 4; PD, progressive disease; PD1, programmed death-1; PR, partial response; SD, stable disease.

Figure 3

PFS (A) and OS according to immunotherapy agent in two trials of stereotactic body radiation therapy given with either anti-CTLA4 or anti-PD1 for metastatic non-small cell lung cancer. CTLA4, cytotoxic T-lymphocyte-associated protein 4; OS, overall survival; PD1, programmed death-1; PFS, progression-free survival.