Efficacy of durvalumab and safety by treatment period in MATTERHORN: A randomized, phase 3 study of durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy in resectable gastric/gastroesophageal junction (G/GEJ) cancer.

4070 Background: In MATTERHORN (NCT04592913), perioperative durvalumab (D) + FLOT significantly improved event-free survival (EFS) and overall survival vs placebo (Pbo) + FLOT in participants (pts) with resectable G / GEJ cancer. Here, we report EFS by treatment period completion status. Methods: In this global, double-blind, Phase 3 study, pts with histologically confirmed, resectable, untreated G / GEJ adenocarcinoma were randomized 1:1 to D 1500 mg or Pbo every 4 weeks (Q4W) on Day 1 + FLOT every 2 weeks on Days 1 and 15 for 4 cycles (2 cycles each neoadjuvant and adjuvant adjuvant: 4–12 weeks post-surgery), followed by D 1500 mg or Pbo Q4W for 10 additional cycles (adjuvant monotherapy). EFS (time from randomization to progression, local or distant recurrence, or death) was assessed by treatment period completion status (Table). Safety was also assessed. Landmark EFS rates were calculated by the Kaplan–Meier method. Hazard ratios and their confidence intervals were estimated by the Cox proportional hazards model. Results: The number of pts who received treatment in each period was similar in the D + FLOT and Pbo + FLOT treatment arms (Table). EFS landmark rates at 12 and 24 months were highest in pts who completed all adjuvant D / Pbo in both arms; EFS was improved in the D + FLOT vs Pbo + FLOT arm irrespective of treatment periods started / completed (Table). A smaller proportion of Grade 3 – 4 adverse events (AEs) and serious AEs (SAEs) were reported in the adjuvant monotherapy period with D + FLOT and Pbo + FLOT (Grade 3 – 4: 21.2% and 20.5%; SAEs: 14.5% and 14.5%, respectively) when compared with the overall treatment period (Grade 3 – 4: 71.6% and 71.2%; SAEs: 48.2% and 44.1%, respectively). In the adjuvant monotherapy period, the rate of any AEs leading to discontinuation of D / Pbo was 5.8% in the D + FLOT vs 2.7% in the Pbo + FLOT arm. Conclusions: EFS landmark rates were greatest for pts who completed the full adjuvant regimen compared with those who discontinued prematurely in both arms. Moreover, the addition of D to FLOT improved EFS regardless of treatment periods started / completed. Safety was manageable and tolerable in the adjuvant monotherapy period. Clinical trial information: NCT04592913 . Received any neoadjuvant treatment but did not complete surgery (N=132) Received any neoadjuvant treatment and completed surgery (N=96)* Received any adjuvant treatment but did not complete D / Pbo (N=223) Completed all adjuvant D / Pbo (N=493) D + FLOT (n=62) Pbo + FLOT (n=70) D + FLOT (n=48) Pbo + FLOT (n=48) D + FLOT (n=116) Pbo + FLOT (n=107) D + FLOT (n=248) Pbo + FLOT (n=245) EFS landmark rate, % 12 mo 16.0 8.3 59.0 41.6 67.4 66.4 99.6 98.8 24 mo 10.0 6.2 49.2 33.3 46.7 29.8 91.8 87.2 EFS hazard ratio (95% CI) 0.80 (0.55–1.18) 0.65 (0.38–1.13) 0.65 (0.46–0.91) 0.63 (0.41–0.97) *These pts did not receive adjuvant treatment.