Progression-free survival benefit appears consistent in patients with recurrent or metastatic cervical cancer treated with tisotumab vedotin.
Treatment with tisotumab vedotin-tftv (Tivdak) resulted in a statistically significant and clinically meaningful overall survival (OS) benefit vs chemotherapy in patients with second- or third-line recurrent or metastatic cervical cancer, according to data from the phase 3 innovaTV 301/ENGOT-cx12/GOG-3057 (NCT04697628) that were originally presented at the 2023 European Society for Medical Oncology (ESMO) Congress and subsequently at the 2023 Annual Global Meeting of the International Gynecologic Cancer Society (IGCS).
The median OS among patients treated with tisotumab vedotin was 11.5 months (95% CI, 9.8-14.9) compared with 9.5 months (95% CI, 7.9-10.7) in the chemotherapy arm (HR, 0.70; 95% CI, 0.54-0.89; P = .0038). The 12-month OS rate was 48.7% vs 35.3% in each respective arm. The median follow-up was 10.8 months (95% CI, 10.3-11.6).
“These data support that tisotumab vedotin should be a potential standard of care for patients with recurrent or metastatic cervical cancer with disease progression on or after systemic first-line therapy,” Brian Slomovitz, MD, director of gynecologic oncology at Mount Sinai Medical Center, said during the presentation.
Patients were able to participate in the global, open-label trial if they had recurrent or metastatic cervical cancer and experienced disease progression during or following doublet chemotherapy with or without bevacizumab (Avastin) and an anti–PD-L1 therapy. Treatment with 2 or fewer previous lines of therapy, evidence of measurable disease per RECIST v1.1 criteria, and an ECOG performance status of 0 to 1 were also required.
Investigators included a total of 502 patients who were randomly assigned 1:1 receive treatment with either tisotumab vedotin at a dose of 2.0 mg/kg intravenously every 3 weeks (n = 253) or chemotherapy (n = 249); options for chemotherapy treatment included topotecan, vinorelbine, gemcitabine, irinotecan, and pemetrexed.
The study’s primary end point was OS, with key secondary end points including progression-free survival (PFS), overall response rate (ORR), and safety.
Investigators reported that baseline demographics and disease characteristics were well balanced across both cohorts. Most patients in the tisotumab vedotin and chemotherapy cohorts, respectively, had extra pelvic metastases (89.3% vs 90.4%), 1 prior systemic regimen (62.8% vs 59.8%), previous treatment with bevacizumab (64.8% vs 63.1%), and underwent prior cervical cancer radiotherapy (81.0% vs 81.5%). Among those with an evaluable biopsy, 92.4% (n = 194/210) of patients who received tisotumab vedotin and 94.3% (n = 183/194) of those who received chemotherapy had positive membrane tissue factor expression.
In terms of other study findings, investigators reported an overall response rate of 17.8% (95% CI, 13.3%-23.1%) in the experimental arm compared with 5.2% (95% CI, 2.8%-8.8%) in the control arm. The disease control rate in each respective arm was 75.9% (95% CI, 70.1%-81.0%) compared with 58.2% (95% CI, 51.8%-64.4%).
Investigators also reported a median PFS of 4.2 months (95% CI, 4.0-4.4) in the experimental arm compared with 2.9 months (95% CI, 2.6-3.1) in the control arm (HR, 0.67; 95% CI, 0.54-0.82; P <.0001). Additionally, the 12-month PFS rate was 30.4% vs 18.9% in each respective group.
Slomovitz reported that the OS and PFS benefits with tisotumab vedotin extended to key patient subgroups, and were considered consistent across the overall patient population.
Incidence of any-trade treatment-related adverse effects (TRAEs) was comparable across treatment groups. Most TRAEs in the experimental group were low grade. AEs of special interest were consistent with known safety signals; these included ocular, peripheral neuropathy, and bleeding events.
Any-grade TRAEs occurred in 87.6% of those in the tisotumab vedotin arm and 85.4% of those in the chemotherapy arm, with high-grade TRAEs occurring in 29.2% and 45.2%, respectively. The most common any-grade TRAEs in each respective arm included anemia (12.8% vs 43.9%) and neutropenia (6.4% vs 21.8%).
Slomovitz BM, Martin AG, Fujiwara K, et al. innovaTV 301/ENGOT-cx12/GOG-3057: a global, randomized, open-label, phase 3 study of tisotumab vedotin vs investigator's choice of chemotherapy in 2L or 3L recurrent or metastatic cervical cancer. Presented at 2023 Annual Global Meeting of the International Gynecologic Cancer Society; November 5-7, 2023; Seoul, Korea; abstract SE006/1616