MAPK Mutations Linked to Better PFS, OS in Low-Grade Serous Ovarian Carcinoma

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Patients with low-grade serous ovarian/peritoneal carcinoma (LGSOC) have significantly better outcomes if they have MAPK-mutated tumors, according to research presented at the SGO 2022 Annual Meeting on Women’s Cancer.

MAPK mutations were associated with improved progression-free survival (PFS) and overall survival (OS), said David M. Gershenson, MD, of the University of Texas MD Anderson Cancer Center in Houston, when presenting this research at the meeting.

Dr Gershenson and colleagues had previously found that LGSOC patients with KRAS or BRAF mutations had significantly longer OS than patients with wild-type KRAS/BRAF.


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With the current study, the researchers set out to determine if other MAPK mutations are associated with outcomes in LGSOC patients as well. The researchers looked specifically at KRAS, NRAS, BRAF, MAP2K1, and RAF1

The team sequenced samples from 215 patients with LGSOC, using either an MD Anderson platform (n=149) or commercial platforms (n=66). 

There were 113 patients who had MAPK-mutated tumors and 102 who did not. The most common mutations were KRAS, NRAS, and BRAF

The median PFS was 31.4 months for patients with MAPK mutations and 23.7 months for patients without them (P =.002). The median OS was 147.8 months and 89.5 months, respectively (P =.01).

Dr Gershenson noted that because there is no universal definition for what constitutes a MAPK mutation, the researchers also looked at NF1 alone and included NF1, NF2, ERBB2, and EGFR in the MAPK-mutated tumor cohort, and results were unchanged. 

In a multivariable analysis, improved PFS was associated with early stage disease, primary cytoreductive surgery, and MAPK-mutated tumors. 

Less favorable OS was associated with stage IV disease and neoadjuvant chemotherapy. Improved OS was associated with being 35 years or older, having a prior diagnosis of serous borderline tumor, receiving primary therapy, and having MAPK-mutated tumors. 

Dr Gershenson highlighted data showing that younger patients had worse prognosis, even if they had MAPK mutations. For patients younger than 35 years, 32.6% had MAPK-mutated tumors and a median OS of 86.5 months. For patients age 35 and older, 58.0% had MAPK-mutated tumors and a median OS of 136.7 months.

“We must accelerate our efforts to discover better treatments for women, particularly younger women whose tumors lack MAPK signaling pathway mutations,” Dr Gershenson concluded. 

Disclosures: Dr Gershenson disclosed relationships with Genentech, Springworks, Onconova, Elsevier, Wolters Kluwer Health, Johnson & Johnson, Bristol Myers Squibb, and Procter and Gamble. 

Reference

Gershenson DM, Sun CC, Westin SN, et al. The genomic landscape of low-grade serous ovarian/peritoneal carcinoma (LGSOC) and its impact on clinical outcomes. Presented at SGO 2022; March 18-21, 2022. Abstract LBA 7.



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