Sintilimab and anlotinib combination therapy in PD-L1-positive recurrent/metastatic cervical carcinoma: A 3-year follow-up of ALTER-C201 study.

e17526 Background: Sintilimab plus Anlotinib has been shown to be effective in advanced cervical cancer in the ALTER-C201 Study. Here, we report an updated, post-hoc analysis of overall survival from ALTER-C201 Study, after 3 years of follow-up. Methods: ALTER-C201 study was a multicenter, single-arm, prospective phase II trial. Patients with PD-L1–positive (Combined Positive Score ≥ 1) R/M CA who progressed after at least one prior systemic chemotherapeutic regimen or could not tolerate chemotherapy were eligible for the phase II trial. The patients received 200 mg sintilimab once on day 1 and 10 mg anlotinib once daily on days 1-14 every 3 weeks. The second endpoint was OS. The post-hoc analysis included Duration of Response (DoR), second progression-free survival (PFS2), as well as the efficacy of other treatments received by patients after disease progression. Results: Between December 2019 and December 2020, 42 patients were enrolled. We followed up for 38.0 (range, 0.6 - 44.0) months. The median overall survival was 17.59 months (95% CI, 12.831-36.163). Through multivariable analysis, it was found that PIK3CA (HR 3.430; 95%CI 1.040 - 11.310; P = 0.043) and KMT2C (HR 0.236; 95%CI 0.056 - 0.998; P = 0.049) are independent prognostic factors associated with overall survival (OS). In post-hoc analysis, the median DoR was 19 months (95%CI, 8.66 - not reach). Thirteen patients who experienced disease progression were subsequently treated with other anti-tumor therapies. Among them, nine received chemotherapy, three received radiotherapy, four received combination therapy with immune checkpoint inhibitors. The median PFS2 was 23.56 months (95%CI, 14.045 - not reach). The overall response rate (ORR) was 53.84%, with 2 patients (15.38%) achieving complete response (CR) and 5 patients (38.46%) achieving partial response (PR), Among the 4 patients who received immune checkpoint inhibitors, 3 of them achieved a partial response (PR). Conclusions: Sintilimab plus Anlotinib showed durable antitumor activity in patients with heavily pre-treated, PD-L1-positive advanced cervical cancer. PIK3CA and KMT2C may serve as potential prognostic biomarkers, but further studies are needed to validate their effectiveness. Patients who experience progression after treatment with the sintilimab plus anlotinib may still benefit from treatment with chemotherapy or combination therapy of other immune checkpoint inhibitors. Clinical trial information: ChiCTR1900023015.