Abstract 921P
Background
Recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) bears a dismal prognosis. Although checkpoint inhibitors (CPI) demonstrated efficacy in R/M HNSCC, only a subset of patients benefits. Taxane based CPI combination therapy might improve the outcome. Thus, we performed this prospective phase I/II trial to investigate the efficacy and safety of docetaxel (DTX) plus pembrolizumab (P) in this setting.
Methods
Patients with R/M HNSCC of the oropharynx, hypopharynx, larynx or oral cavity, who failed prior platinum therapy, were included. Patients received DTX 75mg/mˆ2 plus P 200mg, q21, for up to six cycles followed by P maintenance therapy for a maximum of two years. The primary endpoint was overall response rate (ORR) and safety. Patients were monitored for response every 12 weeks employing iRECIST criteria. Secondary endpoints comprised disease control rate (DCR), overall survival (OS) and progression free survival (PFS).
Results
Twenty-two patients were enrolled. The median age was 63 (44-77) years. Nine patients (40.9%) had a primary tumor in the oropharynx, 8 (36.4%) in the oral cavity, 3 (13.6%) in the hypopharynx and 2 (9.1%) in the larynx. While 4 (50%) oropharyngeal carcinoma patients were p16 positive, all patients showed PDL-1 expression defined as a combined positive score (CPS) ≥1. The ORR was 22.73% (95% CI 10.12%-43.44%) and one (4.5%) complete response was achieved. Disease control occurred in 12 patients resulting in a DCR of 54.55% (95% CI 34.6%-73.08%). The median PFS was 5.8 months (95% CI 2.7-11.6) and the median OS 20.4 months (95% CI 6.3-NR). The 1 year PFS and OS rates were 27.3% and 68.2%, respectively. While the most frequent adverse event (AE) was myelosuppression, which was reported in all 22 patients, 3 (13.6%) patients experienced grade 3 febrile neutropenia. The most common immune related AEs were grade 1/2 fatigue (68.2%), skin rash (40.9%) and hypothyroidism (40.9%). One patient (4.5%) experienced grade 5 immune thrombocytopenia.
Conclusions
DXT in combination with P shows promising activity accompanied with a manageable side effect profile in pre-treated R/M HNSCC patients and warrants further investigations in larger clinical trials.
Clinical trial identification
NCT02718820.
Editorial acknowledgement
Legal entity responsible for the study
Medical University of Vienna.
Funding
Merck Sharp & Dohme.
Disclosure
T. Fuereder: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Sharp & Dohme; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Amgen; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Merck Darmstadt; Honoraria (self): Accord; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Pfizer; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Sanofi; Honoraria (self), Honoraria (institution): Bristol-Myers Squibb; Honoraria (self), Honoraria (institution): Roche; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim. C. Minichsdorfer: Honoraria (institution), Travel/Accommodation/Expenses: Merck Sharp & Dohme; Honoraria (self), Honoraria (institution): Boehringer Ingelheim; Honoraria (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses: Merck Darmstadt; Honoraria (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb. F. Oberndorfer: Honoraria (self): Merck Sharp & Dohme. All other authors have declared no conflicts of interest.