Mirvetuximab Soravtansine Elicits Benefits in Ovarian Cancer Regardless of Dose Modifications

Mirvetuximab soravtansine-gynx (Elahere) generated clinically meaningful improvements in progression-free survival (PFS), overall response rate (ORR), and overall survival (OS) vs investigator’s choice of chemotherapy in patients with folate receptor alpha (FRα)–positive, platinum-resistant ovarian cancer who required dose modifications during the phase 3 MIRASOL trial (NCT04209855), according to findings from post-hoc analyses of the study presented at 2024 ESMO Gynecological Cancers Congress.¹

Among patients in MIRASOL who received modified doses of mirvetuximab soravtansine (n = 124), the median PFS was 7.23 months (95% CI, 5.85-8.48) vs 5.59 months (95% CI, 4.34-6.47) in those who received modified doses of investigator’s choice of chemotherapy in the control arm (n = 114; HR, 0.58; 95% CI, 0.43-0.78; nominal P = .0002).

“Dose modifications should be considered to maximize the potential of remaining on mirvetuximab soravtansine and also then having the opportunity to derive benefit,” Susana Banerjee, MBBS, MA, PhD, FRCP, a consultant medical oncologist and research lead of the Gynaecology Unit at The Royal Marsden NHS Foundation Trust in London, United Kingdom, said in the presentation.

MIRASOL was an open-label trial that enrolled 453 patients with platinum-resistant ovarian cancer that was FRα high and high-grade serous who had received 1 to 3 prior lines of therapy. Patients were allowed to have received prior bevacizumab (Avastin) and PARP inhibitors, and patients with BRCA mutations were permitted to enroll. Patients with first platinum-refractory disease were excluded.

Patients were randomly assigned 1:1 to receive either mirvetuximab soravtansine at 6 mg/kg per adjusted ideal body weight every 3 weeks (n = 227) or investigator’s choice of chemotherapy (n = 226). Patients were stratified by the type of prior investigator’s choice chemotherapy they had received (paclitaxel vs pegylated liposomal doxorubicin [PLD] vs topotecan) and number of prior lines of therapy (1 vs 2 vs 3).

Investigator-assessed PFS served as the primary end point. Key secondary end points included ORR as assessed by the investigators, OS, and the primary patient-reported outcome analysis. Other secondary end points included safety and tolerability, duration of response, CA-125 response, and time to second progression.

In the MIRASOL trial, mirvetuximab soravtansine elicited significant and clinically meaningful survival improvements in PFS (HR, 0.65; 95% CI, 4.3-5.9; P < .0001) and OS (HR, 0.67; 95% CI, 0.50-0.88; P = .0046) vs investigator’s choice of chemotherapy.² Based on these findings, in March 2024, mirvetuximab soravtansine was granted full FDA approval for the treatment of adult patients with FRα-positive, platinum-resistant ovarian cancer who have received 1 to 3 prior systemic therapies.

In MIRASOL, 55% of patients who received mirvetuximab soravtansine and 50% of those who received chemotherapy had dose modifications, defined as dose delays, reductions, or interruptions from day 1 of cycle 1 onward.¹ Therefore, investigators conducted post-hoc analyses to determine the effect of dose modifications on the safety and efficacy of mirvetuximab soravtansine and chemotherapy, as well as to provide data on the safety and efficacy of these agents in patients who had dose modifications in the MIRASOL trial.

Among the patients in the mirvetuximab soravtansine arm who had dose modifications, the median age was 63 years (range, 32-88), and 15% had BRCA mutations. Furthermore, 36%, 55%, and 100% of patients had prior exposure to bevacizumab, PARP inhibitors, and taxanes, respectively. Most patients had a primary platinum-free interval of 12 months or less (63%) or a platinum-free interval of more than 3 months but less than or equal to 6 months (55%). In total, 12%, 40%, and 48% of patients had received 1, 2, and 3 prior lines of therapy, respectively. Forty-four percent, 35%, and 21% of patients had received prior paclitaxel, PLD, and topotecan, respectively.

Among the patients in the chemotherapy arm who had dose modifications, the median age was 64 years (range, 29-87), and 18% had BRCA mutations. Furthermore, 45%, 59%, and 100% of patients had prior exposure to bevacizumab, PARP inhibitors, and taxanes, respectively. Most patients had a primary platinum-free interval of 12 months or less (56%), and 49% of patients had a platinum-free interval of 3 months or less. In total, 10%, 41%, and 49% of patients had received 1, 2, and 3 prior lines of therapy, respectively. Fifty-four percent, 23%, and 24% of patients had received prior paclitaxel, PLD, and topotecan, respectively.

In the mirvetuximab soravtansine and chemotherapy arms, the respective ORRs were 60% (95% CI, 50.5%-68.4%) and 26% (95% CI, 18.5%-35.4%), translating to an ORR difference of 33.4% (95% CI, 21.5%-45.2%; odds ratio, 4.14; 95% CI, 2.39-7.18; nominal P < .0001). Best overall responses in the mirvetuximab soravtansine arm included complete response (8.1%), partial response (51.6%), stable disease (35.5%), progressive disease (4.0%), and not evaluable (NE; 0.8%). These respective rates in the chemotherapy arm were 0.0%, 26.3%, 53.5%, 15.8%, and 4.4%.

The median OS was 20.2 months (95% CI, 17.4-NE) with mirvetuximab soravtansine vs 13.1 months (95% CI, 11.4-16.7) with chemotherapy (HR, 0.45; 95% CI, 0.30-0.68; nominal P = .0001).

Regarding safety, all patients in both arms had any treatment-emergent adverse effects (TEAEs). In the mirvetuximab soravtansine arm, 53% of patients had grade 3 or higher TEAEs, 24% of patients had serious AEs, and 1 patient died during treatment or within 30 days of their last dose of the study drug. Moreover, 59%, 85%, and 10% of patients had dose reductions, delays, and discontinuations, respectively, due to TEAEs. In the chemotherapy arm, 72% of patients had grade 3 or higher TEAEs, 39% of patients had serious AEs, and 2 patients died during treatment or within 30 days of their last dose of the study drug. Moreover, 42%, 82%, and 22% of patients had dose reductions, delays, and discontinuations, respectively, due to TEAEs.

The most common TEAEs in the mirvetuximab soravtansine arm were neutropenia (any-grade, 17%; grade ≥3, 2%), anemia (12%; 2%), thrombocytopenia (6%; 2%), peripheral neuropathy (24%; 2%), alopecia (2%; 0%), diarrhea (26%; 2%), nausea (26%; 2%), stomatitis (5%; 0%), blurred vision (56%; 12%), keratopathy (48%; 15%), and dry eye (40%; 6%). The most common TEAEs with control paclitaxel were neutropenia (any-grade, 44%; grade ≥3, 31%), anemia (44%; 15%), thrombocytopenia (5%; 0%), peripheral neuropathy (34%; 7%), alopecia (31%; 0%), diarrhea (34%; 2%), nausea (30%; 3%), stomatitis (11%; 0%), blurred vision (3%; 0%), and dry eye (5%; 0%). The most common TEAEs with control PLD were neutropenia (any-grade, 15%; grade ≥3, 4%), anemia (8%; 0%), peripheral neuropathy (15%; 0%), alopecia (8%; 0%), diarrhea (4%; 0%), nausea (35%; 0%), stomatitis (15%; 4%), blurred vision (4%; 0%), and dry eye (8%; 0%). The most common TEAEs with control topotecan were neutropenia (any-grade, 63%; grade ≥3, 48%), anemia (70%; 33%), thrombocytopenia (78%; 44%), alopecia (4%; 0%), diarrhea (%; 2%0), nausea (41%; 4%), stomatitis (11%; 0%), and blurred vision (4%; 0%).

“[Mirvetuximab soravtansine] is the new standard of care for patients with FRα-positive platinum-resistant ovarian cancer, and I very much hope that we will have access [to this agent] beyond the United States as soon as possible,” Banerjee concluded.

Mirvetuximab soravtansine is currently under investigation in patients with platinum-sensitive ovarian cancer, both as monotherapy and in combination with other agents.

References

Banerjee S, Van Gorp T, Konecny GE, et al. Safety and efficacy results in patients who received dose modifications in the phase III MIRASOL (GOG 3045/ENGOT-ov55) trial of mirvetuximab soravtansine vs investigator’s choice chemotherapy (ICC) in platinum-resistant ovarian cancer (PROC) with high folate receptor-alpha expression. Presented at: 2024 ESMO Gynecological Cancers Congress; June 20-22, 2024; Florence, Italy. Abstract 44O.

FDA approves mirvetuximab soravtansine-gynx for FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. FDA. Accessed March 22, 2024. Accessed June 21, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mirvetuximab-soravtansine-gynx-fra-positive-platinum-resistant-epithelial-ovarian