Mirvetuximab Soravtansine Gains Traction in Heavily Pretreated FRα+ Platinum-Sensitive Ovarian Cancer

Although mirvetuximab soravtansine-gynx (Elahere) continues to be evaluated in earlier treatment lines and various combinations, it is also poised to become an effective treatment option in the third line and beyond for patients with folate receptor alpha (FRα)–positive recurrent, platinum-sensitive ovarian cancer, particularly those with resistance to PARP inhibitors, according to Angeles Secord, MD, MHSc.

Findings from the phase 2 PICCOLO trial (NCT05041257), which were presented at the 2024 ESMO Congress, reinforce the agent’s efficacy in this heavily pretreated patient population.1 Among all patients (n = 79), the overall response rate (ORR) with mirvetuximab soravtansine was 51.9% (95% CI, 40.4%-63.3%); this included a complete response rate of 7.6%, a partial response rate of 44.3%, stable disease in 36.7% of patients, and progressive disease in 8.9%. The median duration of response (DOR) was 8.25 months (95% CI, 5.55-10.78), and the median time to response was 1.58 months.

Moreover, mirvetuximab soravtansine generated responses across all key subgroups. Notably, in patients who were previously treated with (n = 64) or progressed on a prior PARP inhibitor (n = 59), the ORRs were 46.9% (95% CI, 34.3%-59.8%) vs 45.8% (95% CI, 32.7%-59.2%), respectively. Median DORs were 8.4 months (95% CI, 7.0-not reached) and 7.33 months (95% CI, 5.03-10.78) in patients without progressive disease on a prior PARP inhibitor vs with, respectively. Regarding safety, the agent demonstrated a differentiated safety profile with primarily low-grade toxicities.

“[These data show] that mirvetuximab soravtansine offers a very viable treatment option for those patients who are heavily pretreated, had BRCA mutations, received a prior PARP inhibitor, or received prior bevacizumab [Avastin],” Secord said in an interview with OncLive®.

In the interview, Secord, who is a professor of obstetrics and gynecology at Duke Cancer Institute in Durham, North Carolina, highlighted key efficacy findings from the phase 2 PICCOLO trial, advised on the best way to manage toxicities associated with mirvetuximab soravtansine, and emphasized the importance of testing for FRα expression in ovarian cancer.

OncLive: What key efficacy findings from the PICCOLO trial were presented at the meeting?

Secord: PICCOLO is a phase 2 global, open-label, single-arm, study of mirvetuximab soravtansine in individuals with heavily pretreated platinum-sensitive ovarian cancer. The key primary end point was investigator-assessed ORR, and we found that the response rate was 51.9% in this very heavily pretreated patient population. The key secondary end point was DOR. In this trial, we saw that the DOR was over 8 months.

How did response rates with mirvetuximab soravtansine compare across key subgroups?

When we conducted our sensitivity analysis across various subgroups, we found that mirvetuximab soravtansine works in patients who have platinum-sensitive disease and across all the subgroups. In patients who had a BRCA mutation or had not been previously treated with a PARP inhibitor, the response rates were over 70%. For patients who had previously been treated with and progressed on a PARP inhibitor, the response rate was 45.8%. The other group that’s important is the bevacizumab-pretreated population, where the response rate was [49%].

What was the safety profile of mirvetuximab soravtansine in this trial?

The good news is that the safety profile was very tolerable, and there were no new safety signals. In fact, the incidence of grade 3 or higher adverse effects [AEs] was very low. The most common AEs we saw were mild gastrointestinal toxicity, neurosensory toxicity, and reversible ocular events.

How would you recommend managing these toxicities?

In terms of the ocular events, it’s important to have conversations with your patients about what they should expect, and then have [a conversation] with the physician or provider who’s going to be performing the ocular exams. I work closely with an optometrist, and he’s been wonderful in helping me treat patients. It is also incredibly important to counsel patients about the use of a steroid and lubricating eye drops.

Are any further investigations planned for this research?

The findings from the study are very provocative and promising. In terms of the ORR, [among] patients who were heavily pretreated and have been treated with and progressed on a PARP inhibitor, the response rate was higher than what we would have anticipated, given some of the prior reports of diminished response in that group who gets treated with subsequent therapy. The results are exciting to explore further in that specific patient population, and [provide] an option for all of our patients who have heavily pretreated platinum-sensitive disease.

Why is it important to test patients with ovarian cancer for FRα expression?

In terms of FRα, it is incredibly important to get testing done for our patients. Understanding the level of FRα expression will help us determine the next best treatment for [patients] for them to have the highest chance of receiving benefit from a therapy, and it really helps me in terms of determining the sequence of therapy.

Reference

Secord AA, Corr BR, Lewin S, et al. Mirvetuximab soravtansine (MIRV) in recurrent platinum-sensitive ovarian cancer (PSOC) with high folate receptor-alpha (FRα) expression: results from the PICCOLO trial. Ann Oncol. 2024;35(suppl 2):S549-S550. doi:10.1016/j.annonc.2024.08.780