Randomized Phase II Trial of Nivolumab With Stereotactic Body Radiotherapy Versus Nivolumab Alone in Metastatic Head and Neck Squamous Cell Carcinoma

Abstract

Purpose: The objective response rate (ORR) for single-agent anti-programmed death receptor 1 (anti-PD-1) therapy is modest in patients with metastatic or recurrent head and neck squamous cell carcinoma (HNSCC). We aimed to test whether radiotherapy may act synergistically with anti-PD-1 therapy to improve response through the abscopal effect.

Patients and methods: We conducted a single-center, randomized, phase II trial of nivolumab (anti-PD-1 therapy) versus nivolumab plus stereotactic body radiotherapy (SBRT) in patients with metastatic HNSCC. Patients had at least two metastatic lesions: one that could be safely irradiated and one measurable by RECIST version 1.1. Patients were randomly assigned (1:1), stratified by human papillomavirus status, to nivolumab (3 mg/kg intravenously every 2 weeks) or nivolumab (same dose) plus SBRT (9 Gy × 3) to 1 lesion. The primary end point was ORR in nonirradiated lesions, which was assessed by RECIST in patients with at least one available set of on-treatment images; safety was assessed in a per-protocol population.

Results: Between March 11, 2016, and June 22, 2018, 62 patients were randomly assigned to nivolumab (n = 30) or nivolumab plus SBRT (n = 32). There was no statistically significant ORR difference between arms (34.5% [95% CI, 19.9% to 52.7%] v 29.0% [95% CI, 16.1% to 46.6%]; P = .86). There was no significant difference in overall survival (P = .75), progression-free survival (P = .79), or response duration (P = .26). Grade 3-5 toxicities were similar (13.3% v 9.7%; P = .70).

Conclusion: We found no improvement in response and no evidence of an abscopal effect with the addition of SBRT to nivolumab in unselected patients with metastatic HNSCC.

Trial registration: ClinicalTrials.gov NCT02684253.

Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

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Sean McBride

Consulting or Advisory Role: Janssen Pharmaceuticals, AstraZeneca

Research Funding: Genentech

Eric Sherman

Consulting or Advisory Role: Cota Healthcare, Goldilocks, Eisai, Regeneron Pharmaceuticals, UpToDate, Eli Lilly

Research Funding: Plexxikon

C. Jillian Tsai

Honoraria: Varian Medical Systems

Shrujal Baxi

Employment: Flatiron Health

Stock and Other Ownership Interests: Roche

Jahan Aghalar

Consulting or Advisory Role: Bayer AG, Janssen Oncology

Speakers’ Bureau: Janssen Oncology, Sanofi, EMD Serono

Travel, Accommodations, Expenses: Bayer AG

Loren Scott Michel

Research Funding: Exelixis (Inst)

Travel, Accommodations, Expenses: Immunomedics

Robert Young

Stock and Other Ownership Interests: Alexion, Agios, Biogen, Celgene, Gilead Sciences, Karyopharm Therapeutics, Spark Therapeutics, Regeneron Pharmaceuticals, Stemline Therapeutics, Vertex, Merck, Amgen

Consulting or Advisory Role: Agios, Puma Biotechnology, NordicNeuroLab, ICON Clinical Research

Research Funding: Agios (Inst)

Daniel Spielsinger

Stock and Other Ownership Interests: Guardant Health

Lara Dunn

Consulting or Advisory Role: Regeneron Pharmaceuticals, CUE Biopharma,

Research Funding: Pfizer, Regeneron Pharmaceuticals, Eisai

Alan Ho

Consulting or Advisory Role: Bristol Myers Squibb, Eisai, Genzyme, Merck, Novartis, Sun Pharma, Regeneron Pharmaceuticals, TRM Oncology, Ayala Pharmaceuticals, AstraZeneca, Sanofi, CureVac, Prelude Therapeutics, Kura Oncology, McGivney Global Advisors

Speakers’ Bureau: Medscape, Omniprex America, Novartis

Research Funding: Eli Lilly, Genentech, Roche, AstraZeneca, Bayer AG, Kura Oncology, Kolltan Pharmaceuticals, Eisai, Bristol Myers Squibb, Astellas Pharma, Novartis, Merck, Pfizer, Ayala Pharmaceuticals, Allos Therapeutics, Daiichi Sankyo, Elevar

Travel, Accommodations, Expenses: Janssen Oncology, Merck, Kura Oncology, Ignyta, Ayala Pharmaceuticals, Klus Pharma

Nadeem Riaz

Honoraria: PeerView

Consulting or Advisory Role: Mirati Therapuetics

Speakers’ Bureau: Illumina

Research Funding: Bristol Myers Squibb, Pfizer

Travel, Accommodations, Expenses: Varian Medical Systems

David Pfister

Consulting or Advisory Role: Boehringer Ingelheim, Incyte

Research Funding: Boehringer Ingelheim (Inst), AstraZeneca (Inst), Exelixis (Inst), Novartis (Inst), MedImmune (Inst), Merck (Inst), Genentech (Inst), Roche (Inst), Eli Lilly (Inst), Bayer AG (Inst), Eisai (Inst), Regeneron Pharmaceuticals (Inst), Atara (Inst), Meira (Inst), Hookipa (Inst)

Nancy Lee

Consulting or Advisory Role: Merck, Pfizer, Merck Serono, Sanofi

Research Funding: AstraZeneca, Pfizer (Inst)

No other potential conflicts of interest were reported.

Figures

FIG 1.

Trial profile. SBRT, stereotactic body radiotherapy.

FIG 2.

Overall survival (OS) in the intention-to-treat population (n = 62). Nivo, nivolumab; SBRT, stereotactic body radiotherapy.

FIG 3.

Overall survival (OS) by programmed death-ligand 1 (PD-L1)–positive (+) or –negative (−) status (n = 58).