PROs Strengthen Case for Mirvetuximab Soravtansine as SOC in FRα+ Ovarian Cancer

Gottfried E. Konecny, MD

Patient-reported outcomes (PROs) from the phase 3 MIRASOL trial (NCT04209855) showed that patients with folate receptor-alpha (FRα) positive, platinum-resistant ovarian cancer treated with mirvetuximab soravtansine (Elahere) had a better health-related quality of life (HRQOL) compared with the investigator’s choice of chemotherapy. Along with previously reported survival data, this positions mirvetuximab soravtansine as a new standard of care for this patient population, according to data presented at the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer.¹

Utilizing the abdominal and gastrointestinal (GI) symptom scale of the European Organization for Research and Treatment-QOL questionnaire and ovarian cancer specific model (EORTC QLQ-OV28), researchers found in the primary PRO analysis that 21% (n = 34) treated with mirvetuximab soravtansine met the end point of a 15-point improvement on the survey at week 8/9 compared with 15% (n = 23) in the chemotherapy arm (P = .2611). Further, in a sensitivity analysis of PRO improvement on the EORTC QLQ-OV28 scale, 29% (n = 47) of patients treated with mirvetuximab soravtansine met the 11-point improvement threshold compared with 18% (n = 27) in the chemotherapy arm at week 8/9 (P = .0318).¹

Utilizing a score ranging from 0-100, the EORTC QLQ-OV28 survey consists of 6 items including abdominal pain, bloating, clothes feeling too tight, bowel habits, gas/flatulence, and feeling full too quickly after eating, explained Gottfried E. Konecny, MD, who presented these PRO results at the SGO meeting. To define what result is considered clinically meaningful, they followed the recommendation of the FDA and other regulatory authorities. A pre-specified anchor-based analysis was then performed.

They did this by defining a cut-off around a single question of, what is your quality of life? The answers ranged from very poor to being very bad, and 2 steps of improvement was considered clinically meaningful for this patient population. They then performed the sensitivity analysis, which balanced sensitivity and specificity for discriminating between a responder and a non-responder, according to Konecny, professor in the department of medicine and hematology/oncology at the UCLA Health Jonsson Comprehensive Cancer Center. An 11-point change in the EORTC QLQ-OV28 score was deemed clinically meaningful.

“Overtime, patients that received mirvetuximab soravtansine had a significant decrease in abdominal symptoms over 8, 16, and 24 weeks with a P-vaule of .004, .002, and .0056, [respectively],” said Konecny.

At weeks 8/9, 15/16, and 24 a decrease in symptom score was seen in the mirvetuximab soravtansine compared with symptoms worsening in the investigator’s choice chemotherapy arm at -3.2 (95% CI, -5.5 to -0.8), -2.9 (95% CI, -5.2 to -0.6), and -2.7 (95% CI, -5.4 to 0.1) vs 1.8 (95% CI, -0.7-4.3), 2.5 (95% CI, 0.0-5.0), and 3.3 (95% CI, 0.1-6.6), respectively.1

“Now, these are nominal P-values, that means they are good for an exploratory analysis, but not as a key secondary end point,” he added. “But these data do allow me to conclude that patients treated with mirvetuximab soravtansine are more likely to maintain, or improve, their ovarian cancer specific HRQOL measure, particularly as it pertains to abdominal symptoms and GI symptoms.”

This PRO assessment was done after the MIRASOL trial met its primary end point of progression-free survival (PFS) and the key secondary end points of objective response rate (ORR) and overall survival (OS).2 The global, confirmatory, open-label, randomized, controlled trial, enrolled 453 patients and randomized them 1:1 to receive either 6 mg per kilogram of adjusted ideal body weight of mirvetuximab soravtansine every 3 weeks (n = 227) or investigator’s choice of chemotherapy (n = 226).

Median PFS in the mivetuximab soravtansine arm was 5.62 months (95% CI, 4.34-5.95) compared with 3.98 months (95% CI, 2.86-4.47) in the investigator’s choice of chemotherapy arm (HR 0.65; 95% CI, 0.52-0.81, P <.0001).²

Responses also favored the mirvetuximab soravtansine arm with an ORR of 42.3% (95% CI, 35.8%-49.0%) compared with 15.9% (95% CI, 11.4%-21.4%) in the chemotherapy arm.2 Between the 2 arms there was an ORR difference of 26.4% (95% CI, 18.4%-34.4%), which was found to be significant with an odds ratio of 3.81 (95% CI, 2.44-5.94, P <.0001). The median OS in the mirvetuximab soravtansine was 16.46 months (95% CI, 14.46-24.57) vs 12.27 months (95% CI, 10.91-14.36) in the chemotherapy arm (HR 0.67; 95% CI, 0.50-0.89, P =.0046).²

Safety also favored the antibody drug conjugate, targeting FRα in patients with ovarian cancer resistant to 1-2 lines of prior chemotherapy.2 Fewer grade 3 adverse events (AEs) occurred for patients on mirvetuximab soravtansine compared with chemotherapy at 41.7% vs 54.1%, respectively. Further, more patients discontinued treatment on chemotherapy compared with mirvetuximab soravtansine at 15.9% vs 9.2%, respectively.²

“With these [PRO] data, in line with improved PFS, ORR, and OS, it is fair to say that mirvetuximab soravtansine can be considered a new standard of care in patients with FRα-positive platinum-resistant ovarian cancer,” concluded Konecy.

References

1. Konecny GE, Moore KN, Lebreton C, et al. Patient-reported outcome results from phase III MIRASOL trial of mirvetuximab soravtansine versus investigator's choice of chemotherapy in FRα-positive, platinum-resistant ovarian cancer. Presented at: Society of Gynecologic Oncology 2024 Annual Meeting on Women’s Cancer; March 16-18, 2024; San Diego, CA.

2. Moore KN, Angelergues A, Konecny GE, et al; Gynecologic oncology group partners and the european network of gynaecological oncological trial groups. Mirvetuximab soravtansine in FRα-positive, platinum-resistant ovarian cancer. N Engl J Med. 2023;389(23):2162-2174. doi:10.1056/NEJMoa2309169