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Background Surgical salvage is often the only potentially curative treatment in patients with recurrent head and neck squamous cell carcinoma (HNSCC). However, local control rates after salvage remain at 33-50% with a dismal long term overall survival of 20-40%. Many patients are ineligible for re-irradiation and chemotherapy alone has no survival benefit after salvage surgery necessitating new therapies. Although immune checkpoint inhibitors have demonstrated clinical activity in the metastatic setting, immunotherapy has not been explored after salvage surgery. Therefore, we initiated a multi-center Phase II investigation of adjuvant nivolumab after salvage resection in HNSCC patients (NCT03355560) supported by BMS. Methods HNSCC patients who failed definitive radiation, subsequently treated with curative intent salvage resection, were enrolled to receive 6 months of nivolumab beginning 4 to 11 weeks after surgery. Safety was evaluated with CTCAE v5.0 and disease free survival (DFS) was evaluated using time to event endpoints and Kaplan-Meier curves. Results Eighteen of 35 planned patients have been enrolled. Median age is 70 years (range, [45-85]), 4/18 (22%) were female, 17/18 (94%) were white, disease sites included oropharyngeal 3/18 (17%), oral cavity 8/18 (44%) and larynx 7/18 (39%), and 5/18 (28%) had high risk (positive margins or extranodal spread) pathological features. Four patients have recurred with DFS estimated at 55% at 10.2 months. Although estimated DFS is less than the predicted 62.3% DFS at 10.2 months (extrapolated from 2-year DFS of 33%), the chi-square p-value was 0.861 suggesting there is not enough evidence to reject the null hypothesis and the trial should proceed to the 2nd stage. Most common adverse events included fever (22%), fatigue (17%), arthralgias (22%), cough (28%) and infections (28%) most of which were unrelated. Grade 3 related events included arthralgia and cough. Conclusions Adjuvant nivolumab after salvage surgery in HNSCC patients is safe however, increased enrollment is required to establish efficacy. Clinical trial identification NCT03355560. Legal entity responsible for the study Trisha Wise-Draper. Funding BMS. Disclosure T. Wise-Draper: Research grant / Funding (self): BMS; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Merck; Research grant / Funding (institution): Tesaro. All other authors have declared no conflicts of interest.

Background Patients with metastatic head and neck squamous cell carcinoma (HNSCC) have a poor prognosis, limited treatment options, and median survival of 6 to 9 months. Paclitaxel (TAX) and gemcitabine (GEM) have both shown activity in HNSCC. The optimal combination, dosing, and scheduling of both drugs is, however, unknown. Thus, we investigated the efficacy and safety of biweekly dose-intense GEM/TAX in patients with recurrent locoregional or metastatic HNSCC. Methods An open-label, single-institution, single-arm, phase II study was conducted for patients (pts) who were previously treated with no more than two cytotoxic regimens. The pts received paclitaxel (150 mg/m2IV) and gemcitabine (3000 mg/m2 IV) on day 1 and 15. The treatments were repeated every 28 days (one cycle), until disease progression or unacceptable toxicity. The primary end point was response rate. RECIST-defined response was evaluated every 2 cycles (8 wks) and toxicities were evaluated after each cycle (4 wks). Results Fifty-five pts were enrolled into the trial (M: F 42:13, median age (range): 56 years (23-84), performance status 0-2, 48 pts had previous radiation therapy and 39 had previous surgery), 41 of whom were response evaluable. Of these 41 patients, two pts (4.8%) achieved complete response (CR) and 17 (41.4%) demonstrated a partial response (PR). Thus, the overall response rate was 46%. Thirteen pts (31.7%) had stable disease (SD), resulting in tumor control in 32 of 41 pts (78% with CR, PR or SD), whereas 9 pts (21.1%) had disease progression (PD). Among those pts who achieved objective response or stable disease, the median response duration was 5 months and median time to progression was 4 months. Median overall survival (OS) was 15 months. Myelosuppression was the most common adverse event. Grade 3-4 neutropenia and anemia were observed in 5 (12%) and 11 (26%) pts, respectively. Eight (19%) pts developed grade 3 infection. None of these pts, however, had febrile neutropenia and there were no treatment-related deaths. Conclusions The combination of biweekly dose intense GEM/TAX was tolerable and active regimen in patients with recurrent locoregional or metastatic HNSCC. Our findings warrant further investigation in a larger patient population. Disclosure All authors have declared no conflicts of interest.