655MO - Quality of life in patients with p16+ oropharyngeal cancer receiving accelerated radiotherapy (RT) with either cisplatin or cetuximab in NRG/RTOG 1016

Background

This phase 3 randomized non-inferiority de-escalation trial compared cetuximab (cetux) vs cisplatin (cis), concurrent with accelerated RT 70 Gy/6 weeks, in p16+ oropharyngeal cancer (OPC). Quality of life (QOL) was an important secondary endpoint.

Methods

EORTC QLQ-C30/HN35 was completed at baseline, end of treatment, 3, 6, and 12 months post. The substudy aimed for 400 eligible patients. We report completion rates and compare by arm for change from baseline in each domain (0.05 two-sided alpha and MID of 10 points) using linear mixed models.

Results

Consent was 91% (381/419 offered substudy); 6 protocol deviations excluded (n=375). No significant differences in patient/tumor characteristics were found by participation status. Completion rates (%) at the 5 times did not differ by arm (cis/cetux): 92/94, 74/77, 76/81, 76/81, and 73/74. The swallowing domain of HN35 (previously reported) did not differ significantly by arm. No significant difference was seen by arm for the 6-mo change from baseline on any domain. At end of RT (only), dry mouth was significantly worse for RT+cetux. At end of treatment, all domains showed statistically and clinically significant mean worsening across both arms except Emotional Functioning, Dyspnea, Diarrhea, and Teeth. Most domains returned within 10 points of baseline by 6 mo, with the following maintaining significant impairment: Senses (taste/smell), Social Eating, Opening Mouth, Dry Mouth, Sticky Saliva. At 12 mo post-treatment, worsening from baseline persisted for Senses, Dry Mouth, Sticky Saliva, and Weight Gain. Pain Killer use improved significantly from baseline to 3, 6, and 12 mo.

Conclusions

Although replacing RT+cis with RT+cetux did not benefit QOL, this study has confirmed the responsiveness of EORTC QLQ-C30/HN35 to the effects of concurrent systemic/RT for OPC. Dry Mouth, Sticky Saliva, and Senses showed large, significant, and persistent impairments, and remain worthwhile targets for future de-escalation efforts. Domains related to eating (Swallowing, Appetite, Nutritional Supplements, Social Eating, Weight Loss) did not show sustained significant impairment on this instrument in this study.

Clinical trial identification

NCT01302834.

Editorial acknowledgement

Legal entity responsible for the study

NRG Oncology.

Funding

This project was supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology).

Disclosure

M.L. Gillison: Financial Interests, Personal, Funding, Consulting: Istari Oncology Inc, LLX Solutions, Llc, Kura Oncology, Mirati Therapeutics, BioNtech AG, Shattuck Labs, INC, EMD Serono, INC, Depiopharm, Merck & Co, Ipsen Biopharmaceuticals Inc, Gilead Sciences, Inc, Bristol-Myers Squibb, Bicara Therapeutics, Bayer Healthcare Pharmaceutics, Genocea Biosciences, Inc, Coherus; Financial Interests, Personal, Invited Speaker: OncLive, Roche; Financial Interests, Personal, Advisory Board: Seagen, Sensei Biotherapeutics, Inc; Financial Interests, Personal and Institutional, Research Grant: Genocea Biosciences, Inc, Bristol-Myers Squibb, Genentech, Kura, Cullinan Labs, Agenus; Financial Interests, Personal, Advisory Board, DSMB: SQZBiotech, BioMimetix, Kura. E.M. Sturgis: Non-Financial Interests, Personal, Member of the Board of Directors, also Exec committee of Board: The Immunization Partnership; Non-Financial Interests, Personal, Research Grant: Trinity, Roche Diagnostics. E.M. Basch: Non-Financial Interests, Personal, Member of the Board of Directors: ASCO; Financial Interests, Institutional, Research Grant: NCI, PCORI; Financial Interests, Personal, Funding, consulting: AstraZeneca, Resilience, Sivan, N-Power, Carevive. S.A. Koyfman: Financial Interests, Personal, Advisory Role, consulting: Merck, Regeneron; Financial Interests, Personal, Invited Speaker: Varian; Financial Interests, Personal, Funding, travel expenses: Castle Biosciences; Financial Interests, Personal, Advisory Board, DSMB: Alpha Tau; Financial Interests, Personal and Institutional, Research Grant: BMS, Merck. J.E. Bates: Financial Interests, Personal, Advisory Board: Castle Biosciences, Galera Therapeutics . P. Torres-Saavedra: Non-Financial Interests, Institutional, Research Grant, NRG Oncology SDMC Grant: US NCI. Q. Le: Financial Interests, Personal and Institutional, Funding, support for group related travel (to NRG retreats): RTOG Foundation; Non-Financial Interests, Personal, Leadership Role, RTOG Group Chair: NRG Oncology. B. Movsas: Financial Interests, Personal, Research Grant: Varian, Philips, ViewRay. All other authors have declared no conflicts of interest.