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Background Patients (pts) not candidates to platinum-based therapies have limited therapeutic options. The addition of P to PTX followed by RT + P may be an alternative to platinum-based therapy. This study aimed to evaluate the activity of P + PTX as induction treatment (Tx) in pts with LAHNC. Methods Phase II, single arm, multicenter study, in pts≥18 years with CT/RT-naive stage III-IVb LAHNC not candidates to aggressive Tx. All pts received PTX (80 mg/m2/week [w]) + P (6 mg/kg every 2w) during 9w as induction Tx followed by P and RT (70 Gy/35 fractions/7w).The primary endpoint was RR after induction Tx. With a Simon’s two stage design, p1 at the end of the study was defined as > 36 of 61 patients achieving complete (CR) or partial response (PR) to induction Tx. Results The study included 51 pts: median 70 years (range 45-84), 98% men. Reasons for cisplatin ineligibility: > 70 years old in 3 pts, mild or moderate adult comorbidity [ACE-27 comorbidity index] in 46 pts, severe adult comorbidity in 1 pt and ECOG: 2 in 1 pt. RR after induction was 66.7% (95% confidence interval [CI]: 53.7-79.6): 8 (15.7%) CR and 26 (51.0%) PR. Median progression-free survival was 12.2 months (m) (95% CI: 7.6 - 35.0] and median overall survival was 31.5 m (95%: 14.3 - not reached) with a median duration of follow-up of 31.9 m (range, 1-61). Incidence of grade 3/4 P and/or PTX-related Adverse Events (AEs) was 72.5%. Most frequent grade 3/4 P and/or PTX- related AEs (>5% of pts) were: 5.9% dermatitis, 5.9% neutropenia, 5.9% dry mouth, 5.9% stomatitis, 7.8% asthenia, 15.7% eruption, 15.7% skin toxicity and 27.5% mucosal inflammation. Five (9.8%) pts had fatal AEs, 2 (3.9%) of them related to P and/or PTX. Conclusions Despite the study ended prematurely, the RR observed is higher than the pre-specified boundary to consider the treatment active to justify further studies. PTX combined with P as induction Tx provide a clinically significant benefit with an acceptable safety profile. Clinical trial identification 2012-003038-17. Editorial acknowledgement Marta Munoz-Tuduri (TFS, S.L.). Legal entity responsible for the study Study carried out by Grupo Espanol de Tratamiento de Tumores de Cabeza y Cuello (TTCC). Funding Amgen S.A. Disclosure J. Martinez Trufero: Advisory / Consultancy: PharmaMar, Merck, Lilly, Eisai, Bristol-Myers; Honoraria (self), Medical meetings sponsor: PharmaMar, Merck, Lilly, Eisai. R. Mesia Nin: Advisory / Consultancy: Merck, BMS, MSD, AZ, Roche, Nanobiotix; Speaker Bureau / Expert testimony: Merck, BMS, MSD. M. Taberna Sanz: Non-remunerated activity/ies: Merck; Non-remunerated activity/ies: AstraZeneca; Honoraria (self): Merck; Honoraria (self): Nanobiotics; Honoraria (self): MSD; Honoraria (self): Bristol Myers. J. Lambea Sorrosal: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck-Serono, MSD, Bristol. All other authors have declared no conflicts of interest. L. Iglesias: Honoraria (self), Advisory / Consultancy: Merck Serono, MSD, BMS, Bayer, Sanofi; Honoraria (self), medical education with honoraria: Merck Serono, MSD, AstraZeneca y BMS; Research grant / Funding (institution): Merck Serono, MSD, AstraZeneca, BMS, Novartis, Kura Oncology, Sanofi y Kura Oncology. P. Perez Segura: Speaker Bureau / Expert testimony: BMS, Merck. J.J. Cruz-Hernandez: Honoraria (self): Amgen, AstraZeneca, Bristol-Myers Squibb, Novartis, Pfizer, Roche; Advisory / Consultancy, Advisory Board: Bristol-Myers Squibb, Merck, MSD, Roche, Pfizer, Janssen Cilag; Advisory / Consultancy, Consulting: Roche. |
