New Ovarian Cancer Drug Extends Survival in Resistant Disease

— “Note changing” findings for tricky-to-treat patient population

by
Ed Susman, Contributing Creator, MedPage This day
June 4, 2023

CHICAGO — An antibody-microtubule inhibitor conjugate improved survival in selected sufferers with evolved platinum-resistant ovarian cancer as in contrast with customary chemotherapy, representing the principle original drug to attain so in a section III trial for this subtle-to-treat population.

Females in the trial treated with the lately approved drug, mirvetuximab soravtansine (Elahere), experienced a first-rate 1.6-month improvement in development-free survival (PFS) and a nearly 4-month be triumphant in in median total survival (OS) versus those assigned to physician’s selection of chemotherapy, reported Kathleen N. Moore, MD, of the Stephenson Most cancers Center on the College of Oklahoma in Oklahoma City.

The outcomes will doubtless be “apply changing,” she stated at some point of a press convention right here on the American Society of Clinical Oncology (ASCO) annual meeting.

“There has never been a presentation or a clinical trial of a original agent in the platinum-resistant dwelling that has demonstrated improvement in total survival, till now,” stated Moore, noting that bevacizumab’s 2014 approval in this environment was as soon as in accordance to a PFS merit on my own.

The so-known as MIRASOL trial included 453 females with platinum-resistant, evolved excessive-grade epithelial ovarian, fundamental peritoneal, or fallopian tube cancers and excessive folate receptor α (FRα) expression. While most excessive-grade serous ovarian cancers categorical FRα, about 35-40% of tumors comprise excessive stages of expression, she stated.

Response to remedy was as soon as very a lot higher with mirvetuximab soravtansine (42%, including 12 full responses) versus chemotherapy (12%, no full responses, P<0.0001), and the survival improvement was as soon as equivalent regardless of prior bevacizumab publicity, Moore reported.

“Right here is in actual fact crucial for our sufferers,” stated ASCO-designated professional Merry Jennifer Markham, MD, of the College of Florida in Gainesville. “The MIRASOL recognize is apply changing for this population of females who comprise platinum-resistant ovarian cancer and this folate receptor α excessive expression.”

She explained that over time, females with platinum-resistant ovarian or fallopian tube cancers are usually resistant to other chemotherapy alternatives as successfully.

“These females by some means could want their customary chemotherapy, but this permits the prolong and suspending of those toxic therapies that all americans knows comprise a extraordinarily heart-broken survival curve,” stated Markham. “Females are completely delighted to prolong toxic chemotherapy after they’re facing this prognosis.”

She added that till now, the most attention-grabbing suggestion for subsequent remedy in this population has been enrollment in a clinical trial. “These females had been ready a lengthy time for growth, and I deem this MIRASOL recognize is growth.”

Moore fundamental that the drug has also shown activity in sufferers with decrease stages of FRα expression as successfully.

To be eligible for the recognize, females needed to had been diagnosed with excessive-grade serous, platinum-resistant disease, and comprise FRα detected in no decrease than 75% of tumor cells. Sufferers had been also required to comprise undergone one to a pair old strains of remedy, with prior publicity to bevacizumab and PARP inhibitor remedy allowed. BRCA-particular sufferers had been eligible to signal up as successfully, Moore stated.

Females in the recognize had been about age Fifty three years and roughly 60% had been diagnosed with stage III cancer at their preliminary prognosis. Nearly all had beforehand been treated with taxanes, approximately 60% had a historic past of bevacizumab remedy, and about 55% had been treated with PARP inhibitors.

Eligible sufferers had been randomized 1:1 to either mirvetuximab soravtansine (6 mg/kg each and each 3 weeks) or investigator’s selection of chemotherapy — paclitaxel, pegylated liposomal doxorubicin, or topotecan. Sufferers had been stratified by the make of chemotherapy and by replace of strains of old chemotherapy.

In the fat recognize population, the median PFS was as soon as 5.62 months in the mirvetuximab soravtansine arm as in contrast with 3.98 months in the chemotherapy arm, representing a 35% reduction in the threat for disease development or loss of life (HR 0.65, 95% CI 0.52-0.81, P<0.0001).

OS reached 16.46 months with the recognize drug versus 12.75 months with chemotherapy, a 33% reduction in the threat for loss of life over the course of the trial (HR 0.67, 95% CI 0.50-0.89, P=0.0046).

In females who had obtained bevacizumab, the PFS was as soon as 36% higher in the mirvetuximab soravtansine arm, while OS was as soon as 26% higher. For folks that had now not, PFS was as soon as 34% higher and OS was as soon as 49% higher with the antibody-microtubule inhibitor conjugate.

The security profile of mirvetuximab soravtansine was as soon as often in accordance to prior reports, with negative events (AEs) predominantly consisting of low-grade gastrointestinal and ocular toxicity, including blurred imaginative and prescient (41%), keratopathy (32%), and dry ticket (28%).

Grade ≥3 AEs had been less frequent with mirvetuximab soravtansine (42% vs 54% with customary chemotherapy) as had been serious AEs (24% vs 33%). While extra sufferers on mirvetuximab soravtansine had dose reductions for AEs (34% vs 24%), fewer discontinued remedy for toxicity (9% vs 16%).

“It be so successfully tolerated, the hematologic toxicity is nil, and it in actual fact works,” stated Moore.