Mirvetuximab soravtansine improves survival in platinum-resistant ovarian cancer

Treatment with mirvetuximab soravtansine, an antibody-drug conjugate (ADC) targeting folate receptor-alpha (FRα), led to significantly better survival outcomes in women with platinum-resistant ovarian cancer (PROC) compared with the investigator’s choice of chemotherapy, according to the MIRASOL trial presented at ASCO 2023.

The MIRASOL study met its primary endpoint, demonstrating a statistically significant improvement in investigator-assessed progression-free survival (PFS) with mirvetuximab soravtansine vs investigator’s choice of chemo in this cohort of patients, said lead author Dr Kathleen Moore from Stephenson Cancer Center at the University of Oklahoma, US.

This global phase III trial evaluated 453 PROC patients with high FRα expression who had received 1–3 prior lines of chemotherapy. Participants were randomized 1:1 to receive mirvetuximab soravtansine 6 mg/kg adjusted to ideal body weight (median age 63 years) or investigator’s choice of chemo* (median age 62 years). Sixty-two percent of patients received prior bevacizumab while 55 percent had received PARP** inhibitors. [ASCO 2023, abstract LBA5507]

At a median follow-up of 13.1 months, patients on mirvetuximab soravtansine had significantly improved PFS than those on chemo, translating to a 35-percent reduction in the risk of death (median 5.62 vs 3.98 months; hazard ratio [HR], 0.65; p<0.0001).

Regarding key secondary endpoints, objective response rate (ORR) was higher with mirvetuximab soravtansine than with chemo (42 percent vs 16 percent; odds ratio [OR], 3.81; p<0.0001). “Mirvetuximab soravtansine more than doubled the response rate, which was highly statistically significant,” Moore noted.

These trends favouring mirvetuximab soravtansine over chemo were similarly seen in the BICR*** assessment (median 5.9 vs 4.3 months; HR, 0.72; p=0.0082 [PFS] and 82 percent vs 33 percent; OR, 3.22; p<0.0001 [ORR]). “BICR was very consistent for both of these key endpoints with that assessed by the investigator,” Moore said.

More patients on mirvetuximab soravtansine experienced target lesion reduction from baseline as opposed to those on chemo (80 percent vs 55 percent).

Interim OS analysis
Patients treated with mirvetuximab soravtansine had a significant improvement in overall survival (OS), with a 33-percent reduction in the risk of death vs chemo (median 16.46 vs 12.75 months; HR, 0.67; p=0.0046).

“Mirvetuximab soravtansine is the first novel treatment to demonstrate an OS benefit in PROC in a phase III trial,” said Moore.

Exploratory analysis
Median OS and PFS rates remained better with mirvetuximab soravtansine than with chemo in this analysis, both among bevacizumab-naïve (20.2 percent vs 14.4 percent [OS] and 7.0 percent vs 5.6 percent [PFS]) and prior bevacizumab-treated patients (15.4 percent vs 10.9 percent and 4.4 percent vs 3.0 percent, respectively).

Mirvetuximab soravtansine had a very consistent magnitude of benefit over investigator’s choice of chemo, regardless of the tumour’s prior exposure to bevacizumab, Moore noted.

Safety endpoints
Compared with those on chemo, mirvetuximab soravtansine recipients had fewer grade ≥3 treatment-emergent adverse events (TEAEs; 42 percent vs 54 percent), serious AEs (24 percent vs 33 percent), and AEs leading to treatment discontinuation (9 percent vs 16 percent).

Ocular toxicities (eg, blurred vision, keratopathy, dry eyes) were more frequent with mirvetuximab soravtansine than with chemo, but these were mostly low grade. “There are preventative and mitigation strategies that [could reverse these toxicities and allow] medication continuation to maximal benefit,” said Moore.

New standard of care?
“Overall, mirvetuximab soravtansine has demonstrated statistically and clinically significant improvements in PFS, ORR, and OS compared with investigator’s choice of chemotherapy, with a well-tolerated, differentiated safety profile,” said Moore.

“Importantly, mirvetuximab soravtansine is the first ADC for ovarian cancer with proven efficacy and is the only FDA-approved biomarker-directed therapy for PROC,” she continued.

“We believe these data are practice-changing and position mirvetuximab soravtansine as a new standard of care for patients with FRα-positive PROC,” Moore added.

*Paclitaxel, pegylated liposomal doxorubicin, or topotecan

**PARP: Poly ADP-ribose polymerase

***BICR: Blinded Independent Central Review