Treatment with mirvetuximab soravtansine elicited a statistically significant benefit vs investigator’s choice of chemotherapy for the OV28 abdominal/gastrointestinal symptom subscale in patients with folate receptor alpha–positive, advanced ovarian cancer.
Kathleen N. Moore, MD, MS
Treatment with mirvetuximab soravtansine elicited a statistically significant benefit vs investigator’s choice of chemotherapy for the OV28 abdominal/gastrointestinal (GI) symptom subscale in patients with folate receptor alpha (FRα)–positive, advanced ovarian cancer, according to an analysis of patient-reported outcomes (PROs) from the phase 3 FORWARD-1 trial (NCT02631876) presented at the 2022 ESMO Congress.
Findings showed that among PRO-evaluable patients in the intent-to-treat (ITT) population who received mirvetuximab soravtansine (n = 142), 31.7% reported an improvement of at least 15% in OV28 abdominal/GI symptom score at week 8/9, compared with 14.0% of patients in the chemotherapy arm (n = 50; P = .0162).
Additionally, among patients with FRα-high disease, 27.3% of those treated with mirvetuximab soravtansine (n = 88) experienced a symptom score improvement of at least 15%, compared with 13.3% of those treated with chemotherapy (n = 30; P = .1426).
“Improved PROs were observed with mirvetuximab soravtansine treatment compared with IC chemo across multiple symptoms, including chemotherapy [adverse] effects [AEs], sexuality, hair loss, pain severity, body image, and general improvement in ovarian cancer–specific symptoms on the Functional Assessment of Cancer Therapy-Ovarian Symptom Index [FOSI],” lead study author Kathleen N. Moore, MD, MS, the associate director of Clinical Research at Stephenson Cancer Center of the College of Medicine at the University of Oklahoma, and colleagues, wrote in a poster presentation of the data.
Mirvetuximab soravtansine, a first-in-class antibody-drug conjugate consisting of a FRα-binding antibody, cleavable linker, and maytansinoid DM4 payload; previously demonstrated clinically meaningful antitumor activity with a favorable safety profile as monotherapy and in combination for patients with FRα-positive ovarian cancer.
Preplanned and exploratory analyses of PRO data collected during the FORWARD-1 trial were used to determine differences between treatment with mirvetuximab soravtansine and chemotherapy, and to inform collection of PRO data from subsequent trials evaluating mirvetuximab soravtansine.
The open-label, randomized FORWARD-1 trial evaluated mirvetuximab soravtansine vs chemotherapy investigator’s choice of chemotherapy in patients with platinum-resistant, FRα-positive advanced epithelial ovarian cancer (n = 366).
Enrolled patients were randomly assigned to 6 mg/kg of mirvetuximab soravtansine once every 3 weeks (n = 248) or investigator’s choice of chemotherapy (n = 118).
PRO assessments were completed during screening, on day 1 of cycle 1, and every 9 weeks thereafter until disease progression and at the end-of-treatment visit. The OV28 abdominal/GI symptom score assessment consisted of a 28-item ovarian cancer supplemental module developed to augment the EORTC QLQ-C30 questionnaire, which was also given.
The primary objective of the PRO analysis was minimally important difference response in abdominal/GI symptoms at week 8/9 per the OV28 abdominal/GI symptom subscale score. An increase of at least 15 points was defined as improved, and an increase of less than 15 points was not improved. Time to symptom worsening served as a secondary objective.
Among all enrolled patients, the median age in the mirvetuximab soravtansine arm and chemotherapy arm was 64 years (range, 34-89) and 64 years (range, 31-86), respectively. Most patients in both arms had epithelial ovarian cancer (83.5% and 89% in the experimental and control arms, respectively), had an ECOG performance status of 0 (56.9% and 50.8%), received 1 or 2 prior lines of therapy (64.1% and 62.7%), and had high FRα expression (59.3% and 60.2%).
Exposure to prior treatment included platinum in 100% of patients in both arms, paclitaxel in 96.0% and 95.8% of patients bevacizumab (Avastin) in 48.8% and 46.6% of patients, and PARP inhibitors in 17.7% and 16.1% of patients in the mirvetuximab soravtansine arm and chemotherapy arm, respectively.
Additional data showed that in the ITT population, the median time to symptom worsening was 3.5 months for the mirvetuximab soravtansine arm compared with 3.0 months for the chemotherapy arm (P = .6850). Additionally, among the FRα-high population, the median time to symptom worsening was 4.0 months and 2.1 months in the mirvetuximab soravtansine and chemotherapy groups, respectively (P = .0229).
Compared to the chemotherapy arms, patients treated with mirvetuximab soravtansine in the ITT population had a 70% lower likelihood of deterioration of abdominal/GI symptoms (95% CI, 0.15-0.60; P = .0007). Those in the FRα-high subgroup treated with mirvetuximab soravtansine had an 80% lower chance of deterioration of abdominal/GI symptoms (95% CI, 0.10-0.54; P = .0007). Study authors noted that similar results for the likelihood of symptom deterioration with mirvetuximab soravtansine were observed on other OV28 subscales, including chemotherapy AEs, sexuality, hair loss, pain severity, and body image.
An analysis of PROs from the EORTC QLQ-C30 questionnaire also showed that mirvetuximab soravtansine demonstrated a statistically benefit in physical functioning vs chemotherapy in both the ITT and FRα-high populations. In the ITT population, the least squares (LS) mean overall change of mirvetuximab soravtansine from chemotherapy was 4.10 (standard error [SE], 1.96; 95% CI, 0.25-7.96; P = .0369). In the FRα-high population, the LS mean overall change of mirvetuximab soravtansine from chemotherapy was 6.03 (SE, 2.33; 95% CI, 1.42-10.63; P = .0106).
An analysis of FOSI scores found that by cycle 7, 88.9% of patients in the ITT population in the chemotherapy arm declined, compared with 70.3% in the mirvetuximab soravtansine arm. Those rates were 88.1% for the chemotherapy arm and 65% for the mirvetuximab soravtansine arm in the FRα-high population.
Additionally, FOSI scores showed that the median time to symptom worsening was 2.9 months and 2.1 months for the mirvetuximab soravtansine and chemotherapy groups, respectively, in the ITT population (P = .5423). Among those in the FRα-high subgroup, those treated with mirvetuximab soravtansine achieved a median time to symptom worsening of 3.5 months compared with 2.0 months for those given chemotherapy, per FOSI scores (P = .0199).
“These positive PRO findings, in conjunction with the safety profile of mirvetuximab soravtansine in recurrent ovarian cancer [and] along with significant antitumor activity, support mirvetuximab soravtansine as a potential new standard of care for patients with FRα-positive ovarian cancer,” study authors concluded.
Moore KN, Oza AM, Colombo N, et al. Analyses of patient-reported outcomes (PROs) with mirvetuximab soravtansine (MIRV) versus standard chemotherapy in the randomized phase III FORWARD I study in ovarian cancer (GOG 3011). Ann Oncol. 2022;33(suppl 7):S790-S791. doi:10.1016/j.annonc.2022.07.660