Shifting the MIRV Timeline
New study highlights the possibilities of MIRV plus carboplatin in platinum-sensitive ovarian cancer.
Mirvetuximab soravtansine (MIRV) is already established as a treatment for folate receptor-alpha (FRa) positive, platinum-resistant ovarian cancer (PROC) in patients who have had one to three chemotherapy treatments. But a new study suggests it can also be safe and effective to combine with carboplatin in the treatment of PROC, and to continue administering MIRV as a maintenance therapy after treatment with carboplatin.
Today’s late-breaking abstract, “Mirvetuximab soravtansine plus carboplatin in folate receptor alpha-expressing recurrent platinum-sensitive ovarian cancer,” highlighted the results of that trial and demonstrated how MIRV could enhance treatment going forward.
“It’s not a randomized study, so it’s not establishing a new standard of care, but it is the first study to explore a combination with an antibody drug conjugate and a platinum agent, which is novel,” said study author Gottfried Konecny, MD, lead clinician for gynecologic oncology in the Department of Medicine at UCLA. “It’s also the first larger study to explore the utility of a folate receptor targeting [antibody-drug conjugate] as a maintenance therapy in platinum-sensitive disease and provides new information on the feasibility of this treatment approach, its activity and safety.”
Although most folate receptor targeting ADCs that are in clinical development are being assessed in platinum-resistant disease, Dr. Konecny said this study is exploring a new direction of moving the drug up into earlier lines of treatment, combining an ADC with a platinum agent and studying this combination regimen in platinum-sensitive disease.
“The study has many new pieces of information that may not be practice-changing yet, but the information gained from it will inform the field where we are going,” he said.
The study included 125 patients with measurable, recurrent FRa-expressing PSOC and one prior line of platinum-based chemotherapy. Primary and secondary endpoints were objective response rate (ORR) by the end of six combination cycles. Additional secondary endpoints included duration of response, progression-free survival, overall survival, and treatment-emergent adverse events.
The study found that MIRV plus carboplatin in recurrent PSOC with an FRa greater than or equal to 25% can be safely administered with minor dose modifications and proactive adverse event management. It also achieved favorable objective response rates and progression-free survival rates, showed comparable efficacy to pre-poly (ADP-ribose) polymerase (PARP) inhibitor era benchmarks, and established the safety and efficacy of continuing MIRV after carboplatin for the first time. Dr. Konecny said the manageable toxicity rates demonstrated in the study were very encouraging.
“The safety data showed that there were no major toxicities beyond those known for each of these drugs as a single agent,” he said. “We have seen manageable rates of myelotoxicity and otherwise very manageable toxicities.”
Another encouraging finding of the study, Dr. Konecny said, is that most of the patients were pre-treated with maintenance therapy with a PARP inhibitor, which has not been the case for much of the earlier data that has been available in this area.
“We know with maintenance therapy with a PARP inhibitor the response to subsequent platinum-based chemotherapy may not be that good, and our study does confirm that those who received prior PARP inhibitor treatment had somewhat lower clinical response rates,” he said. “But the preliminary data shows those rates may be better that what has been seen for standard platinum-based regimens, so that’s reassuring.”
Dr. Konecny added that these findings highlight the possibility of using the combination of MIRV plus carboplatin, particularly in platinum-sensitive patients whose tumors express more than 25% FOLR1 and who have received a PARP inhibitor following their frontline platinum-based chemotherapy.
The other promising study finding is the responses seemed to deepen when the patients went on to receive the ADC as a maintenance therapy. But Dr. Konecny said it is important to watch for new toxicities that could come along with this prolonged exposure to an ADC.
“It’s of note that the pulmonary toxicity rate in this study was higher than what’s been known for MIRV up to this point,” he said. “The rate of pneumonitis has historically been around 10%, mostly mild in nature. But in this study, particularly for those patients who continued the treatment for a very long time, the rate was 15% — again mostly mild cases, and the majority were reversible. But this is a signal that we have to pay particularly close attention to pulmonary toxicity when we use the drug beyond six cycles of combination chemotherapy as a maintenance. There is also a need for close surveillance and proactive management so that pulmonary toxicities remain mild and reversible.”
Dr. Konecny said he believes the findings in this study support further evaluation of MIRV plus carboplatin as a treatment option in recurrent PSOC. In fact, he said there are some trials going on right now that are doing just that.
“There’s a neoadjuvant study where the combination is being explored, where the response to neoadjuvant chemotherapy could be used as a surrogate marker to assess the activity,” he said. “There are interesting studies going on that are looking at the maintenance therapy in a randomized setting. So [our study] is in line with several trials that are currently ongoing with the intent to move MIRV up into earlier lines where the impact on long-term outcomes may be more significant than when used solely in platinum-resistant disease as a later line of therapy.”
