Neoadjuvant and Adjuvant Nivolumab and Lirilumab in Patients with Recurrent, Resectable Squamous Cell Carcinoma of the Head and Neck.

PURPOSE: Surgery often represents the best chance for disease control in locoregionally recurrent squamous cell carcinoma of the head and neck (SCCHN). We investigated dual immune-checkpoint inhibition [anti-PD-1, nivolumab (N), and anti-KIR, lirilumab (L)] before and after salvage surgery to improve disease-free survival (DFS). PATIENTS AND METHODS: In this phase II study, patients received N (240 mg) + L (240 mg) 7 to 21 days before surgery, followed by six cycles of adjuvant N + L. Primary endpoint was 1-year DFS; secondary endpoints were safety, pre-op radiologic response, and overall survival (OS). Correlatives included tumor sequencing, PD-L1 scoring, and immunoprofiling. RESULTS: Among 28 patients, the median age was 66, 86% were smokers; primary site: 9 oral cavity, 9 oropharynx, and 10 larynx/hypopharynx; 96% had prior radiation. There were no delays to surgery. Grade 3+ adverse events: 11%. At the time of surgery, 96% had stable disease radiologically, one had progression. Pathologic response to N + L was observed in 43% (12/28): 4/28 (14%) major (tumor viability, TV ≤ 10%) and 8/28 (29%) partial (TV ≤ 50%). PD-L1 combined positive score (CPS) at surgery was similar regardless of pathologic response (P = 0.71). Thirteen (46%) recurred (loco-regional = 10, distant = 3). Five of 28 (18%) had positive margins, 4 later recurred. At median follow-up of 22.8 months, 1-year DFS was 55.2% (95% CI, 34.8-71.7) and 1-year OS was 85.7% (95% CI, 66.3-94.4). Two-year DFS and OS were 64% and 80% among pathologic responders. CONCLUSIONS: (Neo)adjuvant N + L was well tolerated, with a 43% pathologic response rate. We observed favorable DFS and excellent 2-year OS among high-risk, previously treated patients exhibiting a pathologic response. Further evaluation of this strategy is warranted.See related commentary by Sacco and Cohen, p. 435.

Observational study of talimogene laherparepvec use in the anti-PD-1 era for melanoma in the US (COSMUS-2).

AIM: Talimogene laherparepvec (T-VEC) is an intralesional therapy for unresectable, metastatic melanoma. T-VEC real-world use in the context of anti-PD1-based therapy requires further characterization. MATERIALS & METHODS: A retrospective review of T-VEC use from 1 January 2017 and 31 March 2018 for melanoma patients was conducted at seven US institutions. RESULTS: Among 83 patients, three categories of T-VEC and anti-PD-1 therapy were identified: T-VEC used without anti-PD-1 (n = 29, 35%), T-VEC after anti-PD-1-based therapy (n = 22, 27%) and concurrent T-VEC and anti-PD-1-based therapy (n = 32, 39%). 25% of patients discontinued T-VEC therapy due to no remaining injectable lesions, 37% discontinued T-VEC due to progressive disease. Discontinuation of T-VEC did not differ by anti-PD-1-based therapy use or timing. CONCLUSION: In real-world settings, T-VEC may be used concurrently with or after anti-PD-1-based therapy.

Etanercept therapy for silicone granuloma.

A patient developed a typical, painful, and debilitating reaction on the thighs following injection of ostensibly medical grade "silicone" to achieve alteration of body contours. The refractory silicone granuloma responded dramatically to treatment with etanercept.