MIRASOL PRO data boost mirvetuximab soravtansine potential in FRα-positive ovarian cancer

Patient-reported outcomes (PROs) from the phase III MIRASOL trial underpin the potential of the antibody drug conjugate mirvetuximab soravtansine (MIRV) to improve health-related quality of life (HRQoL) in women with folate receptor-alpha positive platinum-resistant ovarian cancer (FRα-positive PROC) as opposed to investigator’s choice of chemotherapy.

“MIRASOL was a positive study that met its primary endpoint, which was improvement in progression-free survival (PFS). It also met key secondary endpoints of improved overall survival (OS) and objective response rate (ORR),” said Dr Gottfried Konecny from the University of California, Los Angeles Jonsson Comprehensive Cancer Center, Los Angeles, California, US, during his presentation at SGO 2024.

“We now report on a key secondary endpoint – PROs using the European Organization for Research and Treatment of Cancer – ovarian cancer module (EORTC-OV28) Abdominal/Gastrointestinal (GI) Subscale ,” Konecny continued.

The EORTC-OV28 is a questionnaire specific for ovarian cancer patients consisting of six items: abdominal pain, bowel habits, bloating, gas/flatulence, whether clothing is feeling too tight, and whether a patient is feeling too full after a meal, he explained.

Using this measure in the primary PRO evaluation, Konecny and colleagues found that about a quarter (21 percent) of MIRV recipients met the endpoint of a 15-point improvement at week 8/9 vs 15 percent in the chemotherapy arm, but this did not reach statistical significance (p=0.2611).

However, using the 11-point improvement threshold on sensitivity analysis, the improvement with MIRV compared with chemotherapy met statistical significance (29 percent vs 18 percent; p=0.0318), noted Konecny.

Sustained symptom improvements

An exploratory analysis showed that over time, symptom scores dropped in the MIRV group (changes from baseline in least-squares mean [LSM] score, -3.2, -2.9, and -2.7 at weeks 8/9, 15/16, and 24, respectively). In the chemo arm, the corresponding symptom scores increased (changes from baseline in LSM score, 1.8, 2.5, and 3.3), which equated to worsening of symptoms.

The treatment differences between the MIRV and the chemotherapy arms were -5, -5.4, and -6 at the respective week 8/9, 15/16, and 24 timepoints. These differences corresponded to nominal p-values of 0.0041, 0.0020, and 0.0056, respectively.

Survival benefit

In the initial analysis of MIRASOL, the median PFS with MIRV was 5.62 months as opposed to 3.98 months with chemotherapy (hazard ratio [HR], 0.65, 95 percent confidence interval [CI], 0.52–0.81; p<0.0001). Responses also favoured MIRV over chemotherapy (42.3 percent vs 15.9 percent). The ORR difference of 26.4 percent between arms was deemed significant, with an odds ratio of 3.81 (95 percent CI, 2.44–5.94; p<0.0001). Median OS with MIRV was 16.46 months vs 12.27 months with chemotherapy (HR, 0.67, 95 percent CI, 0.50–0.89; p=0.0046). [N Engl J Med 2023;389:2162-2174]

Konecny highlighted that MIRV is the first novel treatment to demonstrate an OS benefit in a phase III trial on PROC. [ASCO 2023, LBA 5507]

Moreover, MIRV gained the upper hand over chemotherapy in terms of safety, targeting FRα in ovarian cancer patients who were resistant to 1–2 lines of prior chemotherapy. The rate of grade 3 adverse events was lower in the MIRV vs chemotherapy arm (41.7 percent vs 54.1 percent), as was the incidence of treatment discontinuation (9.2 percent vs 15.9 percent).

Poor QoL

Konecny noted that about 35–40 percent of patients with PROC express high levels of FRα. In PROC, patients experience poor HRQoL, which can be due to underlying disease symptoms (such as abdominal/GI symptoms due to ascites, small bowel obstructions, prior surgeries) and treatment-induced adverse events, which include haematologic, neurosensory, and GI symptoms, as well as alopecia.

In MIRASOL, Konecny and his team evaluated 453 women with platinum-resistant disease and FRα detected by immunohistochemistry (with positive staining intensity ≥2 intensity among 75 percent of viable tumour cells). Other key eligibility criteria were high-grade serous histology and 1–3 prior lines of therapy. Patients with BRCA mutations were permitted to enrol, as were those who have been previously treated with bevacizumab and poly (ADP-ribose) polymerase inhibitors.

The participants were randomized 1:1 to either MIRV 6 mg/kg of adjusted ideal body weight Q3W or investigator’s choice of chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan).

A potential SoC in FRα-positive PROC

“[The present] data allow me to conclude that patients treated with MIRV are more likely to maintain or improve their ovarian cancer-specific HR QoL measure, with marked improvements in abdominal/GI symptoms across all timepoints relative to chemotherapy,” said Konecny.

Importantly, the results build upon exploratory findings showing significant HRQoL improvements using the C30 questionnaire in MIRV-treated patients, and HRQoL deterioration among those who received chemotherapy, he added.

“The efficacy and safety of MIRV is supported by the PRO data, thus positioning MIRV as a new SoC for patients with FRα-positive PROC ,” Konecny concluded.