Avelumab alone or in combination with pegylated liposomal doxorubicin versus pegylated liposomal doxorubicin alone in platinum-resistant or refractory epithelial ovarian cancer: Primary and biomarker analysis of the phase III JAVELIN Ovarian 200 trial

Abstract

Objective: Avelumab monotherapy showed modest antitumor activity (objective response rate, ORR, 9.6%) and a manageable safety profile in a phase 1b study of patients with recurrent/refractory ovarian cancer (OC, n = 125). This randomized, open‐label, phase 3 trial (JAVELIN Ovarian 200; NCT02580058) evaluated avelumab (Ave) alone or in combination with pegylated liposomal doxorubicin (PLD) versus PLD alone in patients with platinum‐resistant or refractory OC (PRROC). Method: Eligible women (PRROC, ≤3 prior lines for platinum‐sensitive disease and no prior therapy for platinum‐resistant disease) were randomized 1:1:1 to Ave (10 mg/kg Q2W), Ave plus PLD (40 mg/m2 Q4W), or PLD. Primary endpoints were PFS (by blinded independent central review per RECIST version 1.1) and OS. Retrospective analysis of efficacy based on PD‐L1 status (PD‐L1 expression ≥1% of tumor cells or ≥5% of immune cells) was a secondary endpoint. Results: A total of 566 patients were randomized, including 142 (25%) with platinum‐refractory disease, 273 (48%) with only 1 prior line of therapy, and 210 (37%) with bulky disease (tumor ≥5 cm). At data cutoff (September 19, 2018), all patients had been followed for ≥16 months or had died, withdrew consent, or were lost to follow‐up. Ave did not improve PFS or OS versus PLD, and PFS or OS prolongation with Ave plus PLD versus PLD did not reach significance (Table 1). ORRs were 3.7% (95% CI 1.5–7.5) for Ave, 13.3% (95% CI 8.8–19.0) for Ave plus PLD, and 4.2% (95% CI 1.8–8.1) for PLD. At the time of writing, in patients evaluable for PD‐L1 status (n = 442), median PFS was similar between PD‐L1+ and PD‐L1− subgroups in both the Ave and Ave plus PLD arms but differed in the PLD arm (1.9 vs 3.7 months). In patients with PD‐L1+ tumors (58% of patients), trends for longer PFS and OS were seen for Ave plus PLD versus PLD (Table 1). In the Ave plus PLD arm, the ORR was 18.5% (95% CI 11.1–27.9) in the PD‐L1+ subgroup and 3.4% (95% CI 0.4–11.9) for the PD‐L1− subgroup. No new safety signals were observed; in the Ave, Ave plus PLD, and PLD arms, grade ≥3 treatment‐emergent adverse events occurred in 49.7%, 68.7%, and 59.3% of patients, respectively. Conclusion: Ave plus PLD showed clinical activity in patients with PRROC, but the trial did not meet its primary objectives of significantly improving PFS or OS versus PLD in the overall population. Planned analyses suggested improved PFS and OS for Ave plus PLD versus PLD in the PD‐L1+ subgroup. [Figure presented]