Updated report of a phase II randomized trial of transoral surgical resection followed by low-dose or standard postoperative therapy in resectable p16+ locally advanced oropharynx cancer: A trial of the ECOG-ACRIN cancer research group (E3311).

Document Type


Publication Date


Publication Title

2021 ASCO Annual Meeting


oregon; portland; chiles


Research Funding:

U10CA180820, U10CA180794, UG1CA189953, UG1CA232760, UG1CA233184, UG1CA233196, UG1CA233247, UG1CA233329, UG1CA233331, UG1CA233337, U10CA180863, Canadian Cancer Society #704970

Background:Definitive or postoperative chemoradiation (CRT) is highly curative for human papillomavirus-associated (HPV+) oropharynx cancer (OPC) but induces significant toxicity. As a potential deintensification strategy, we studied primary transoral surgery (TOS) and, in intermediate pathologic risk patients, reduced dose postoperative RT (PORT).Methods:E3311 is a phase II trial with randomization to reduced- or standard-dose PORT for resected stage III-IVa (AJCC7) intermediate pathologic risk HPV+ OPC, stratified by smoking history. Primary endpoints have been reported; we now present updated 3-year PFS and patient-reported outcomes (PRO), including head and neck-cancer specific quality of life (FACT-H&N) and swallowing perception and performance (MDADI).Results:Of 519 enrolled patients, 495 underwent TOS. The primary oncologic endpoint was 2-year PFS for 50 Gy (Arm B) or 60Gy (Arm C). Among 360 eligible and treated patients (ETP), Arm A (observation, N = 38) enrolled 11%, Arms B (N = 100) or C (N = 109) randomized 58%, and Arm D (66Gy + weekly cisplatin, N = 113) enrolled 31%. With 35.1 months median follow-up, 3-year PFS Kaplan-Meier estimate is 96.9% (90% CI [91.9%, 100%]) for Arm A; 94.9% (90% CI [91.3%, 98.6%]) for Arm B; 93.5% (90% CI [89.4%, 97.9%]) for Arm C; and 90.7% (90% CI [86.2%, 95.4%]) for Arm D. Recurrences and death without recurrence were 4 and 1 in Arm B, and 5 and one in Arm C. Smokers ( > 10 pack-years) did not have worse 3-year PFS in Arms B or C. Treatment arm distribution and outcome for ineligible patients who started adjuvant therapy mirrored the 360 ETP. A comparison combining arms B/C versus arm D in the proportion of patients stable/improved in FACT-H&N total score, from baseline to 6 months post-treatment as a pre-specified endpoint, was 56% vs. 38% (p value = 0.011, one-sided Fisher’s exact test); however, underlying differences in treatment and risk may be confounding. An exploratory comparison between Arms B and C revealed improvement in FACT H&N (63% in Arm B vs. 49% in Arm C had a stable/improved score, p-value = 0.056).Conclusions:Primary TOS and reduced PORT retained outstanding oncologic outcome at 35 months follow up, with favorable QOL and functional outcomes, in intermediate risk HPV+ OPC. Clinical trial information: NCT 01898494.

Clinical Institute



Earle A. Chiles Research Institute




Robert L. Ferris, Yael Flamand, Gregory S. Weinstein, Shuli Li, Harry Quon, Ranee Mehra, Joaquin J. Garcia, Jolie Ringash, Jan S. Lewin, Umamaheswar Duvvuri, Bert W. O'Malley, Enver Ozer, Giovana R. Thomas, Wayne Koch, Michael E. Kupferman, Richard B. Bell, Nabil F. Saba, Miriam Lango, Lynne I. Wagner, Barbara Burtness