Data from the phase 3 MIRASOL trial support mirvetuximab soravtansine as a new standard of care for patients with folate receptor α–positive, platinum-resistant ovarian cancer, says Kathleen N. Moore, MD, MS.
Mirvetuximab soravtansine-gynx (Elahere) is the first novel therapy to produce an overall survival (OS) benefit among patients with folate receptor α (FRα)–high, platinum-resistant ovarian cancer in a phase 3 setting, according to exploratory analysis findings from the phase 3 MIRASOL trial (NCT04209855) presented at the 2023 Annual Global Meeting of the International Gynecologic Cancer Society (IGCS).
Among patients who were naïve to treatment with PARP inhibitors, the median OS was 14.82 months (95% CI, 11.33-not reached [NR]) with mirvetuximab soravtansine (n = 97) vs 15.44 months (95% CI, 12.39-17.41) with investigator’s choice of chemotherapy (n = 94; HR, 0.90; 95% CI, 0.59-1.38; P = .6319). Among those who previously received a PARP inhibitor, the median OS was 19.88 months (95% CI, 15.61-NR) in the mirvetuximab soravtansine arm (N = 124) vs 11.37 months (95% CI, 9.89-13.77) in the chemotherapy arm (n = 127; HR 0.48; 95% CI, 0.33-0.71; P = .0002).
In a population of patients who received 1 or 2 prior lines of therapy, the median OS was 16.46 months (95% CI, 12.88-NR) with mirvetuximab soravtansine (n = 122) vs 13.77 months (95% CI, 11.20-16.69) with chemotherapy (n = 123; HR, 0.66; 95% CI, 0.45-0.98; P = .0375). For those who received 3 prior lines of treatment, the median OS was 17.35 months (95% CI, 12.81-20.24) in the mirvetuximab soravtansine arm (n = 105) vs 12.39 months (95% CI, 9.63-13.34) in the chemotherapy arm (n = 103; HR, 0.65; 95% CI, 0.43-0.96; P = .0308).
“[We believe] these data are practice-changing and position mirvetuximab as a new standard of care for patients with FRα-positive platinum-resistant ovarian cancer,” senior author Kathleen N. Moore, MD, MS, associate director of clinical research at Stephen Cancer Center in The University of Oklahoma College of Medicine, said during the presentation.
In the open-label MIRASOL trial, 453 patients were randomly assigned 1:1 to receive mirvetuximab soravtansine at 6 mg/kg every 3 weeks or investigator’s choice of paclitaxel, pegylated liposomal doxorubicin, or topotecan. Patients were stratified by the type of chemotherapy they received and number of prior lines of therapy.
The study’s primary end point was investigator-assessed progression-free survival (PFS), with key secondary end points including investigator-assessed overall response rate (ORR), OS, and patient-reported outcomes. Other secondary end points included duration of response (DOR), PFS2, and safety/tolerability.
Those with platinum-resistant, FRα–high disease as detected via immunohistochemistry; high-grade serous histology; and who previously received 1 to 3 prior lines of therapy were eligible to enroll on the trial. Patients who previously received treatment with PARP inhibitors and bevacizumab (Avastin), as well as those with disease harboring BRCA mutations, were able to enroll on the trial.
According to Moore, a higher proportion of patients in the PARP inhibitor–naïve cohort underwent 1 or 2 previous lines of therapy, although most patients across the entire population received 3 prior lines of treatment. Additionally, it was more probable for those who were PARP inhibitor naïve to have no response to their most recent line of therapy.
In the PARP inhibitor naïve population, the median PFS was 5.39 months (95% CI, 3.32-5.85) vs 4.27 months (95% CI, 2.83-5.52) with mirvetuximab soravtansine and chemotherapy, respectively (HR, 0.74; 95% CI, 0.54-1.03; P = .0685). The median PFS among patients previously treated with a PARP inhibitor was 5.85 months (95% CI, 4.57-7.06) vs 3.91 months (95% CI, 2.60-4.37) in each respective treatment arm (HR, 0.58; 95% CI, 0.43-0.78; P = .0002).
The median PFS among patients who received 1 to 2 prior lines of treatment was 5.68 months (95% CI, 4.96-6.97) with mirvetuximab soravtansine vs 4.04 months (95% CI, 2.83-5.29) with chemotherapy (HR, 0.61; 95% CI, 0.45-0.81; P = .0007). Additionally, investigators reported a median PFS of 4.37 months (95% CI, 3.32-5.85) vs 3.98 months (95% CI, 2.66-4.34) in each respective arm among patients who received 3 prior lines of treatment (HR, 0.71; 95% CI, 0.52-0.98; P = .0362).
Treatment with mirvetuximab soravtansine elicited an ORR of 42% (95% CI, 36%-49%) compared with 16% (95% CI, 11%-21%) among patients who received chemotherapy in the overall population (odds ratio [OR], 3.81; 95% CI, 2.44-5.94; P <.0001).
The ORR in the PARP inhibitor–naïve population was 40% (95% CI, 30%-51%) with the experimental treatment vs 14% (95% CI, 8%-23%) with chemotherapy (OR, 4.19; 95% CI, 2.06-8.54; P <.0001). Among patients previously treated with a PARP inhibitor, the ORR was 45% (95% CI, 36%-54%) vs 17% (95% CI, 11%-25%) in each respective arm (OR, 3.93; 95% CI, 2.20-7.02; P <.0001).
Among patients who received 1 or 2 prior lines of treatment, the ORR was 46% (95% CI, 37%-55%) with mirvetuximab soravtansine vs 15% (95% CI, 9%-22%) with chemotherapy (OR, 4.95; 95% CI, 2.68-9.14; P <.0001). Additionally, the ORR with each respective treatment was 38% (95% CI, 29%-48%) vs 18% (95% CI, 11%-26%) among those previously treated with 3 lines of therapy (OR, 2.91; 95% CI, 1.53-5.53; P = .0009).
Any-grade treatment-emergent adverse effects (TEAEs) affected 96% of patients who received mirvetuximab soravtansine compared with 94% of those who received chemotherapy. Additionally, 9% and 16% of patients in each respective arm discontinued study therapy following TEAEs. According to Moore, mirvetuximab soravtansine demonstrated a favorable safety profile compared with chemotherapy, and that most toxicities associated with the experimental agent consisted of low-grade ocular, neurosensory, and gastrointestinal events.
Van Gorp T, Sabatier R, Konecny GE, et al. Efficacy of mirvetuximab soravtansine in folate receptor alpha high, platinum-resistant ovarian cancer by type and number of prior treatment regimens: an exploratory analysis. Presented at the 2023 Annual Global Meeting of the International Gynecologic Cancer Society (IGCS); November 5-7, 2023; Seoul, South Korea.