MIRV Plus Bevacizumab Feasible For Recurrent Ovarian Cancer

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Preliminary findings suggest that the folate receptor α (FRα) targeted antibody–drug conjugate mirvetuximab soravtansine (MIRV) has manageable tolerability when given in combination with bevacizumab to patients with recurrent ovarian cancer. 

The results from the phase Ib FORWARD II trial cohort were reported at the virtual 2020 ASCO Annual Meeting by Lucy Gilbert, from McGill University Health Centre in Montreal, Quebec, Canada, who explained that MIRV has previously shown “encouraging activity” in platinum-resistant ovarian cancer. 

The current study investigated the tolerability of MIRV when given alongside bevacizumab to women who are candidates for non-platinum doublet therapy for recurrent epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer.  

This included 60 women aged a median of 60 years who had a medium (45%) or high (55%) FRα membrane score on immunohistochemistry. Most (98%) participants had also previously received a taxane, 40% bevacizumab and 32% a PARP inhibitor. 

Patients were given MIRV 6 mg/kg adjusted to ideal bodyweight plus bevacizumab 15 mg/kg on day 1 of a 3-week cycle, the presenter said. 

Around a fifth (22%) of patients discontinued MIRV and/or bevacizumab because of treatment-related adverse events (TRAEs), but most AEs were low-grade. The most common any-grade TRAEs were gastrointestinal side effects such as diarrhoea (68%) and nausea (55%), and blurred vision (63%) that was manageable with lubricating and steroid eye drops.  

The most common grade 3 or more severe TRAEs were hypertension (12%) and myelosuppression (10%). There were no grade 3 cases of the special TRAE pneumonitis, but three grade 1 asymptomatic cases and one grade 2 episode were reported. 

The objective response rate (ORR) for the total cohort was 47%, including 64% of patients with high FRα expression and 26% of those with medium FRα expression. 

And among the high FRα subgroup, the ORR was a comparable 59% and 69% for the patients with platinum-resistant and platinum-sensitive disease, respectively, despite 13% of the platinum-sensitive patients having a platinum-free interval of at least a year.  

“This is important because it shows that our responses were not driven by platinum sensitivity”, commented Lucy Gilbert. 

The majority (92%) of patients experienced a reduction in tumour burden, with the high FRα subgroup experiencing “deeper and more durable” decreases than the medium FRα patients, the presenter said. 

Specifically, the high FRα patients showed responses within 6 weeks of treatment, including one patient with a complete response and four other patients with 100% decrease of target lesions. Almost half (46%) of the high FRα subgroup remain on treatment and both the progression-free survival and overall survival results are immature after a median 8.5 months of follow-up, the investigator told delegates. 

“With a confirmed 64% ORR, the combination of MIRV with bevacizumab has promising activity in high FRα recurrent ovarian cancer, regardless of platinum status, and is encouraging with respect to available therapies reported in similar populations”, concluded Lucy Gilbert. 

She added: “The combination of MIRV and bevacizumab may benefit an increasing population of recurrent ovarian cancer for whom a non-platinum based regimen would be appropriate.” 

Reference  

Gilbert L, Oaknin A, Matulonis UA, et al. Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients (pts) with platinum-agnostic ovarian cancer. J Clin Oncol; 38: suppl; abstr 6004. DOI: 10.1200/JCO.2020.38.15_suppl.6004