NCCN Guidelines Update Adds Mirvetuximab Soravtansine Plus Bevacizumab for FRα-Expressing, Platinum-Sensitive Ovarian Cancer

Mirvetuximab soravtansine (Elahere; Immunogen) plus bevacizumab was added to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology as a 2B recommendation for patients with platinum-sensitive ovarian cancer and folate receptor alpha (FRα)-expressing tumors. The updated guidelines (version 1.2024) also changed mirvetuximab soravtansine plus bevacizumab from a category 2B to a category 2A recommendation for platinum-resistant ovarian cancer with FRα-expressing tumors.

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The regimen was first added to the NCCN Clinical Practice Guidelines in Oncology as a category 2B recommendation for platinum-resistant disease expressing FRα. The change to category 2A from 2B indicates uniform NCCN panel consensus that the intervention is appropriate vs simply consensus.

The FDA granted accelerated approval to mirvetuximab soravtansine for women with platinum-resistant, FRα-positive advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers in November 2022.² The approval was based on results from the SORAYA study, which showed anti-tumor activity, durable responses, and tolerability in patients with FRα-positive, platinum-resistant ovarian cancer. With its accelerated approval, it became the first antibody drug conjugate approved for platinum-resistant disease.

Mirvetuximab soravtansine in combination with bevacizumab has been shown active and well-tolerated, with findings published in Gynecologic Oncology showing an objective response rate of 44% (95% CI, 33-54), median duration of response of 9.7 months (95% CI, 6.9-14.1), and median progression-free survival (PFS) of 8.2 months (95% CI, 6.8-10.0).³

As a single agent, mirvetuximab soravtansine is a category 2A preferred regimen for platinum-resistant disease with tumors expressing FRα.¹

Positive results from the confirmatory MIRASOL trial were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, confirming that mirvetuximab soravtansine confers progression-free survival (PFS) and overall survival (OS) benefits compared with previous standards of care.⁴ At a median follow-up of 13.1 months, patients treated with mirvetuximab soravtansine who had previously received bevacizumab experienced 36% better PFS and 26% better OS vs physician’s choice chemotherapy. Those who had received bevacizumab experienced 34% better PFS and 49% better OS vs chemotherapy.

The full MIRASOL results, published in the New England Journal of Medicine, further demonstrated significantly longer OS and PFS in the mirvetuximab soravtansine cohort compared with physician’s choice chemotherapy.⁵ Median OS was 16.46 months with mirvetuximab soravtansine vs 12.75 months with chemotherapy (HR for death, 0.67; 95% CI, 0.50-0.89; P = .005). In the mirvetuximab soravtansine cohort, 42.3% of patients experienced an objective response, compared with 15.9% in the chemotherapy cohort (OR, 3.81; 95% CI, 2.44-5.94; P < .001).

Other updates in the new guidelines related to recurrence therapy for platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer included the addition of oral cyclophosphamide, pembrolizumab, and bevacizumab as a category 2A regimen in the “other recommended regimens” category; as well as fam-trastuzumab deruxtecan-nxki as a category 2A recommendation for HER2-positive tumors (immunohistochemistry result of 3+ or 2+).¹

References

1. NCCN. Clinical Practice Guidelines in Oncology. Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer, version 1.2024. Accessed January 19, 2024.

2. Joszt L. FDA approves mirvetuximab soravtansine-gynx for platinum-resistant ovarian cancer. AJMC. November 15, 2022. Accessed January 19, 2024. https://www.ajmc.com/view/fda-approves-mirvetuximab-soravtansine-gynx-for-platinum-resistant-ovarian-cancer

3. Gilbert L, Oaknin A, Matulonis UA, et al. Safety and efficacy of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer. Gynecol Oncol. 2023;170:241-247. doi:10.1016/j.ygyno.2023.01.020

4. Caffrey M. MIRASOL: Mirvetuximab soravtansine Improves PFS, OS in certain women with recurrent ovarian cancer. AJMC. June 4, 2023. Accessed January 19, 2024. https://www.ajmc.com/view/mirasol-mirvetuximab-soravtansine-improves-pfs-os-in-certain-women-with-recurrent-ovarian-cancer

5. Moore KN, Angelergues A, Konecny GE, et al. Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer. N Engl J Med. 2023;389(23):2162-2174. doi:10.1056/NEJMoa2309169