Association of Palmar-plantar erythrodysesthesia syndrome (PPES), hypothyroidism, and clinical outcomes in previously treated endometrial cancer (EMC) with pMMR status: A subgroup analysis of FRUSICA-1.

Abstract

e17612 Background: FRUSICA-1(NCT03903705) is an open label, single-arm, pivotal phase II study, demonstrated the promising efficacy and favorable safety of fruquintinib (F) + sintilimab (S) in previously treated advanced EMC patients (pts) with pMMR status, with objective response rate (ORR): 35.6%; median progression-free survival (mPFS): 9.5mo; median overall survival (mOS): 21.3mo (Wu X, et al; 2024 ASCO). PPES and hypothyroidism are two common adverse events in the combination therapy of angio-genesis tyrosine kinase inhibitors and PD-1 antibody. Researches have indicated patients with PPES may experience better treatment outcomes in various cancer types. Immune related adverse events (irAE) were also deemed as predictor of response in gynecologic cancers. Therefore, we launched a subgroup analysis of the treatment outcome in patients who developed PPES or hypothyroidism in FRUSICA-1. Methods: EMC pts with centrally confirmed pMMR status who progressed after ≤ 2 platinum-based systemic therapy were treated with F (5mg QD orally, 2w on/1w off) + S (200mg IV, Q3W), in a 3-week cycle until disease progression or unaccepted toxicity. Patients who developed PPES or hypothyroidism were extracted and the efficacy analysis was then conducted accordingly. Results: As of 15th May 2024, 98 eligible pts were enrolled and evaluated with a median follow-up of 22.0 mo (95%CI: 20.5, 23.7). In the full analysis set (FAS), 38 (38.8%) pts experienced PPES, 45 (45.9%) experienced hypothyroidism. Assessed by independent review committee (IRC), Patients who developed PPES showed numerically higher efficacy with an ORR 47.4% (95% CI: 31.0, 64.2), DCR 92.1% (95% CI: 78.6, 98.3), mPFS and mOS not reached (NR), 15-mo PFS rate 60.7% (95% CI: 39.3, 76.6), 24-mo OS rate 59.3% (95% CI: 40.5, 73.9). Patients who had irAE hypothyroidism, also showed a higher efficacy, with an ORR 44.4% (95% CI: 29.6, 60.0), DCR 93.3% (95% CI: 81.7, 98.6), mPFS 16.6 mo (95% CI: 6.9, 27.4), mOS 24.0 mo (95% CI: 17.7, NR), the maturity of PFS and OS were 53.3% (24/45) and 46.7% (21/45). Conclusions: In FRUSICA-1 study, PPES and irAE hypothyroidism may be associated with higher ORR, longer PFS and OS in advanced EMC patients. PPES and irAE hypothyroidism could potentially be predictive of clinical outcomes for pts with treatment with fruquintinib plus Sintilimab. Clinical trial information: NCT03903705 .