Trabectedin (Yondelis) plus pegylated liposomal doxorubicin (PLD) has similar efficacy as the combination of carboplatin plus PLD in patients with recurrent ovarian cancer whose disease has progressed after their last platinum line, according to research presented at the European Society for Medical Oncology Virtual Congress 2020.
In a phase 3 international randomized study known as INOVATYON, at a median follow-up of 44 months, median overall survival (OS) was 21.5 months versus 21.3 months for the trabectedin plus PLD and carboplatin plus PLD arms, respectively (hazard ratio [HR], 1.10; P = .284), reported Nicoletta Colombo, MD, PhD, Director, Medical Gynecologic Oncology, European Institute of Oncology, Milan, Italy, and Director, Ovarian Cancer High Specialty Center, University of Milano Bicocca, Milan.
Because the study was powered to detect superiority of trabectedin plus PLD on the end point of OS, it did not meet its primary end point. However, trabectedin plus PLD did show a trend toward improved OS in those patients with 2 previous lines of platinum therapy.
“Platinum-based regimens remain the standard of care in patients with recurrent ovarian cancer progressing within 6 to 12 months after last platinum line,” said Dr Colombo. “The similar OS still indicates a possible role for trabectedin pus PLD in patients with multiple previous lines of platinum, who may need a longer recovery time from platinum-specific toxicities.”
PLD had previously demonstrated an improvement in progression-free survival (PFS) over carboplatin plus paclitaxel combination in a similar population in the CALYPSO trial, noted Dr Colombo in laying out the rationale for the INOVATYON study.
A total of 617 patients with relapsed ovarian cancer whose disease progressed within 6 to 12 months after their last platinum line were enrolled in INOVATYON, which was conducted at 117 European sites. Patients were randomized 1:1 to the combination of trabectedin (1.1 mg/m2) plus PLD (30 mg/m2) or carboplatin (area under the curve 5) plus PLD (30 mg/m2). Treatment continued for 6 cycles or until disease progression.
At progression, all patients in the trabectedin plus PLD arm had mandatory platinum rechallenge, whereas subsequent therapy was administered at investigators’ discretion for those in the carboplatin plus PLD arm.
The median treatment-free interval from the last platinum line was 8.4 months in the carboplatin plus PLD arm and 8.3 months in the trabectedin plus PLD arm. Approximately 30% of patients in each arm received 2 previous platinum lines.
Median PFS was statistically longer for carboplatin plus PLD at 9.0 months compared with 7.5 months in patients assigned to the trabectedin plus PLD arm (P = .005).
Approximately three-fourths of patients in each arm received subsequent therapy versus 74.0% in the carboplatin plus PLD arm.
For patients in the trabectedin plus PLD arm, 63.2% received platinum-based subsequent therapy, per protocol, compared with 17.8% of those in the carboplatin plus PLD arm. Poly (ADP-ribose) polymerase inhibitor maintenance was used in 6.6% of the carboplatin plus PLD arm. Median PFS calculated from the start of subsequent therapy was 7.4 months in the trabectedin plus PLD arm versus 5.7 months with carboplatin plus PLD (HR, 0.84; P = .086).
Among the patients who received 1 previous line of treatment, there was a trend toward improved OS in the carboplatin plus PLD arm, whereas in those receiving 2 previous lines, a trend toward improved OS was observed in the trabectedin plus PLD arm.
Grade ≥3 treatment-emergent adverse events were more frequent in the trabectedin plus PLD arm than in the carboplatin plus PLD arm (69% vs 36%). The rate of grade ≥3 neutropenia was 39% for trabectedin plus PLD versus 22% for carboplatin plus PLD (P <.001). Grade ≥3 gastrointestinal adverse events (18% vs 7%; P <.001) and grade ≥3 hepatotoxicity (18% vs 1%; P <.001) were also significantly more likely for trabectedin plus PLD versus carboplatin plus PLD.
Several quality of life end points on the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ)-C30 scale favored carboplatin plus PLD, including fatigue, nausea and vomiting, appetite loss, and global health status. According to the EORTC QLQ-OV28 instrument, attitude to disease/treatment, hormonal/menopausal symptoms, and other chemotherapy side effects again favored carboplatin plus PLD.