869P - Results of the multicenter phase II FRAIL-IMMUNE trial evaluating the efficacy and safety of durvalumab (D) combined with weekly paclitaxel carboplatin in 1st-line in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) not eligible to cisplatin

Background

For patients (pts) with R/M SCCHN, standard of care is pembrolizumab (P) either alone or combined with platin-5FU (KN 048 – median Overall Survival (OS): 13 months when combined). Pts who cannot receive platinum-5FU are treated by P alone or chemotherapy (CT) in monotherapy, with a poor OS. This population is generally excluded from clinical trials. After clinically significant results in patients with Performance Status (PS) ≤1, we investigated the efficacy and tolerance of PD-L1 inhibition with D combined with weekly carboplatin-paclitaxel as 1^st-line in frail R/M SCCHN pts with PS2.

Methods

This single-arm phase II enrolled pts in 1^st-line of their R/M SCCHN, not eligible to cisplatin-based CT, with a PS2. Pts received 4 CT cycles (carboplatin AUC2; paclitaxel 80mg/m² both at D1, D8, D15) and D 1500mg repeated every 4 weeks up to 12 months. The primary endpoint was OS rate at 12 months (m). The study used a A’Hern design (inefficacy boundary: 15% and target efficacy: 35%), requiring 10 successes among 38 pts. Main secondary endpoints were Progression-Free Survival (PFS), objective response rate (ORR) and tolerance.

Results

40 pts (median age 67.0y; 90.0% males) with PS2 were included, regardless of their PD-L1 status. Primary tumors were mainly located in oral cavity (40.0%) and oropharynx (35.0%) with 45.7% PD-L1 CPS>20. 50.0% were metastatic. The efficacy rule for OS was met with 20 pts (51.3%, unilateral 95%CI: [37.1%; - ]) alive at 12m among the 39 evaluable pts. With a median follow-up of 24.7 m, median OS was 12.4 m (95% CI [6.7 – 22.6]) and the 24m-OS rate was 29% [14%-45%]. Median PFS was 5.3 m (95% CI [3.7-7.2]). 23/38 pts (60.5%) achieved an OR (2 complete responses and 21 partial responses). 15.0% of pts experienced G≥3 D-related adverse events. Toxicity led to permanent discontinuation of D in 7.5% of pts. 3 SUSAR were reported (death of unknown cause).

Conclusions

The combination of D with weekly carboplatin/paclitaxel confirms its efficacy and good tolerance in 1^st-line R/M SCCHN and appears as an appropriate option for frail patients with PS2.

Clinical trial identification

GORTEC 2018-03 Sponsor ID: ET18-023 NCT0372967, dated Jan. 28^th, 2019.

Editorial acknowledgement

Legal entity responsible for the study

Centre Léon Bérard.

Funding

AstraZeneca.

Disclosure

J. Fayette: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Innate Pharma, Merck Serono, Roche, Pfizer, Hookipa; Non-Financial Interests, Principal Investigator: AstraZeneca, MSD, Pfizer, Meru, Calliditas, Isa. C. Toullec: Financial Interests, Personal, Invited Speaker: Amgen, BMS, MSD, Pierre Fabre, Viatris; Financial Interests, Personal, Advisory Board: Bayer, Merck Serono, Sanofi, Servier, AstraZeneca, Oncoscience. D. Perol: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Gilead, Ipsen, Pfizer, Novartis, Merck Sharp And Dohme, Roche, Takeda; Financial Interests, Personal, Advisory Board: Brenus Pharma; Other, Travel Expenses (ESMO Annual Meeting Madrid 2023): Novartis; Other, Travel Expenses (ESMO Annual Meeting Paris 2022): Roche. All other authors have declared no conflicts of interest.