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J Immunother Cancer. 2020 Jan;8(1). pii: e000492. doi: 10.1136/jitc-2019-000492.

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.

Author information

1
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
2
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States.
3
Department of radiation oncology, Allegheny General Hospital, Houston, Texas, United States.
4
Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, China.
5
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States JWelsh@mdanderson.org.
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Contributed equally

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

PMID:
31996395
DOI:
10.1136/jitc-2019-000492
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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.

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