Results of the multicenter phase II FRAIL-IMMUNE trial evaluating the efficacy and safety of durvalumab combined with weekly paclitaxel carboplatin in first-line in patients (pts) with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) not eligible for cisplatin-based therapies.
Jérôme Fayette, Claire Cropet, Julien Gautier, Clémence Toullec, Mickaël Burgy, Amandine Bruyas, Christian Sire, Aurélie Lagrange, Florian Clatot, Benoît Calderon, Marie Vinches, Mariana Iacob, Laurent Martin, E. Bérard, Marie‐Christine Kaminsky, Damien Vansteene, Sébastien Salas, Anne Champagnac, David Pérol, Jean Bourhis
Abstract
6003 Background: For pts with R/M SCCHN, new standard of care (SoC) has been recently established with pembrolizumab either alone or combined with platin-5FU (KN 048 – median Overall Survival (OS): 13 months when combined). For pts who need chemotherapy, platinum-5FU-pembrolizumab as first-line treatment appears associated with substantial toxicity that precludes its use in fragile patients. In this context, we investigated the efficacy and tolerance of PDL-1 inhibition with durvalumab combined with weekly carboplatin-paclitaxel as first-line treatment in frail R/M SCCHN pts. Methods: This single-arm phase II study enrolled pts in first-line of their R/M SCCHN and not eligible to standard cisplatin-based CT with an ECOG PS of 0 or 1. Pts received 4 cycles of CT (carboplatin AUC2; paclitaxel 80mg/m² both at D1, D8, D15) and durvalumab (D) 1500mg repeated every 4 weeks for a maximum of 12 months. The primary endpoint was OS Rate at 12 months (m). The study used a Fleming A’Hern design (inefficacy boundary: 47% and target efficacy: 65%), requiring 38 successes among 64 pts. Secondary endpoints were Progression-Free Survival (PFS), Time to Treatment Failure (TTF), objective response rate (ORR) and tolerance. Results: 64 pts (median age 69.5y; 90.6% males, 62.5% PS1) were included, regardless of their PDL-L1 status. Primary tumors were mainly located in oropharynx (37.5%) and larynx (28.1%) with 37.3% PD-L1 CPS≥20. 54.9% were metastatic. The efficacy rule for OS was met with 40 pts (62.5%, unilateral 95%CI: [51.5% - ]) alive at 12m. With a median follow-up of 27.1 m, median OS was 18.0 m (95% CI [11.9-NR]) and the 24m-OS rate was 45% [32%-57%]. Median PFS was 7.0 m (95% CI [5.4-9.9]) and median TTF was 6.0 m (95% CI [4.7-9]). 44/62 pts (71%) achieved an OR (11.3% complete response and 59.7% partial response). Median duration of response was 5.9 m (95% CI [3.4-9.6]). 20.3% of pts experienced G≥3 adverse events related to D, Toxicity led to permanent discontinuation of D in 3.1% of pts. No D-related death was reported. Conclusions: This study performed in fragile patients not amenable to cisplatin-based CT met its primary endpoint on OS and showed a 18 months median OS rate. This combination of durvalumab with weekly carboplatin/paclitaxel was associated with a favorable toxicity profile. Clinical trial information: NCT0372967 .