Mirvetuximab soravtansine is emerging as a promising treatment for patients with heavily pretreated, folate receptor alpha (FRα)-positive, platinum-sensitive ovarian cancer. Data from the phase 2 PICCOLO trial, presented at the European Society for Medical Oncology (ESMO) Congress 2024, reveal clinically meaningful antitumor activity and a favorable tolerability profile, offering hope for a challenging patient population. The study's findings suggest that mirvetuximab soravtansine could fill a critical gap in the treatment landscape for those who have exhausted other options.
Efficacy in Heavily Pretreated Patients
The PICCOLO trial enrolled patients with platinum-sensitive ovarian cancer who had received multiple prior lines of therapy. The overall response rate (ORR) with mirvetuximab soravtansine was 51.9% (95% CI, 40.4%-63.3%), including a complete response rate of 7.6% and a partial response rate of 44.3%. 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. These results are particularly encouraging given the heavily pretreated nature of the patient population.
"I'm very excited about the outcome of the study," said Dr. Angeles Alvarez Secord, professor of obstetrics and gynecology at Duke Cancer Institute and the trial's primary investigator. "The main findings are really that this has high evidence of efficacy in individuals who have FRα-positive, platinum-sensitive ovarian cancer."
Activity in PARP Inhibitor-Resistant Disease
A notable aspect of the PICCOLO trial was the activity of mirvetuximab soravtansine in patients who had previously been treated with and progressed on a PARP inhibitor. In this subgroup, the ORR was 45.8% (95% CI, 32.7%-59.2%), with a median DOR of 7.33 months (95% CI, 5.03-10.78). This finding is significant because PARP inhibitor resistance is a major challenge in ovarian cancer treatment.
"This is a challenging patient population to treat, and the response rate in that group was 45.8%, with a duration of response of over 7 months," Dr. Secord noted.
Safety and Tolerability
Mirvetuximab soravtansine demonstrated a manageable safety profile in the PICCOLO trial. The most common treatment-emergent adverse events (TEAEs) were blurred vision (63%), nausea (37%), and dry eye (37%). However, grade 3 or higher adverse events were rare, and most side effects were mild and tolerable. These included gastrointestinal, neurosensory, and reversible ocular events.
Addressing Unmet Needs
Dr. Secord emphasized the unmet therapeutic needs that mirvetuximab soravtansine could potentially address. In the platinum-sensitive space, a gap exists for heavily pretreated patients who may not be eligible for repeat platinum therapy due to hypersensitivity reactions or bone marrow suppression. Mirvetuximab soravtansine offers a potentially more effective and tolerable alternative to single-agent chemotherapy options like paclitaxel, liposomal doxorubicin, or gemcitabine.
Implications for Clinical Practice
The results of the PICCOLO trial suggest that mirvetuximab soravtansine could become an important tool in the treatment of heavily pretreated, FRα-positive, platinum-sensitive ovarian cancer. The drug's efficacy, even in patients with PARP inhibitor-resistant disease, and its manageable safety profile make it an attractive option for this challenging patient population. Further research is needed to confirm these findings and to explore the optimal sequencing of mirvetuximab soravtansine with other therapies.
