723MO Tisotumab vedotin (TV) + carboplatin (Carbo) in first-line (1L) or + pembrolizumab (Pembro) in previously treated (2L/3L) recurrent or metastatic cervical cancer (r/mCC): Interim results of ENGOT-Cx8/GOG-3024/innovaTV 205 study

Abstract

Methods: Participants with high grade ovarian, fallopian tube, primary peritoneal cancer who relapsed within 12 months of previous platinum-based therapy were randomised, with stratification for germline BRCA1/2 mutation status, prior PARP inhibitor (PARPi) or anti-angiogenic therapy, to receive O (300mg daily) or either wP (80mg/m 2 d1,8,15, q28) or O+C (300mg/20mg daily respectively). Treatment continued until disease progression or unacceptable toxicity. Primary endpoint was Progression Free Survival (PFS). Secondary endpoints were safety and tolerability of the combination of O+C, overall survival, objective response rate, and quality of life. A sample size of 138 (46 per arm) was sufficient to observe HR 0.64 in favour of O+C compared to O alone and 1.44 for wP compared to O (20% one-sided type I error, 80% power, 15% dropout, one-sided p-value <0.2).Results: OCTOVA recruited 139 participants, median 65 years (IQR:38-84), from 15 UK centres over 34 months. 31 (22%) had had prior PARPi therapy, 47 (34%) prior antiangiogenic therapy. 41 (29%) had known germline BRCA1/2 mutations. 125 (90%) had relapsed <6 months after prior platinum. Median 2 prior lines of chemotherapy (range 1-7). There was no difference in PFS between wP and O (HR¼0.97, 60%CI: 0.79, 1.19; p¼0.55). PFS was increased for O+C compared to O (HR¼0.70; 60%CI: 0.57, 0.86; p¼0.08). There were 239, 176, and 137 treatment related adverse events (all grades) in the O+C, wP and O arms respectively. Conclusions:The OCTOVA trial demonstrated that the combination of O+C showed greater efficacy than O alone, but we did not find evidence that wP was inferior to O in women with multiply relapsed OC.

Top advances of the year: Cervical cancer

“…Interest in improving the efficacy of TV in cervical cancer continues, and preliminary results of the combinations of TV with carboplatin and pembrolizumab have been reported. The carboplatin combination (up to one prior line of chemotherapy; ORR, 55%) and the pembrolizumab combination (two to three prior lines; ORR, 35%) were presented at the European Society of Medical Oncology meeting in 2021 16 . Most recently, the interim results of a phase 2 trial in which patients were treated with TV and pembrolizumab if they had not received prior systemic therapy (aside from CRT) were reported at the American Society of Clinical Oncology (ASCO) in 2022 17 .…”

Treatment strategies in cervical cancer: treatment of advanced disease

“…Despite the mitigation measures, ocular treatment-related AEs happened in 54 patients (25 with grade 1 and 27 with grade 2 events). Two patients suffered from a grade 3 AE (ulcerative keratitis) [58] .…”

Advancing antibody-drug conjugates in gynecological malignancies: myth or reality?

“…The ENGOT-Cx8/GOG-3024/innovaTV 205 trials are investigating the efficacy of tisotumab vedotin in combination with carboplatin in first-line treatment of patients with recurrent/metastatic cervical cancer or in combination with pembrolizumab in the second or third line of treatment [ 87 ]. In the first-line setting, the combination of tisotumab vedotin and carboplatin resulted in an ORR of 55% and a mPFS of 9.5 months (4.0–not reached).…”

“…In the first-line setting, the combination of tisotumab vedotin and carboplatin resulted in an ORR of 55% and a mPFS of 9.5 months (4.0–not reached). In the second or third line, the combination of tisotumab vedotin and pembrolizumab showed an ORR of 38% and a mPFS of 5.6 months (2.7–13.7) [ 87 ]. These preliminary results support the continued investigation of tisotumab vedotin for the treatment of cervical cancer.…”