A significant milestone was reached for patients with low-grade serous ovarian cancer (LGSOC). The U.S. Food and Drug Administration granted accelerated approval to a new combination therapy—avutometinib plus defactinib (marketed together)—for adults whose disease has a KRAS mutation and who have already been treated with at least one systemic therapy.

LGSOC is a rare ovarian cancer subtype that responds poorly to standard chemotherapy. Many patients suffer disease progression despite prior treatments and options have been very limited. The approval of this combination represents the first time a therapy has been specifically approved to target KRAS-mutated LGSOC.

Key Clinical Findings

The decision was based on results from a mid-stage (Phase II) trial involving about 57 patients, all of whom had undergone prior therapy. Among them those with KRAS mutations showed especially strong benefit. The overall response rate (ORR) was notably higher in the KRAS-mutant subgroup than in patients without that mutation. The therapy also showed acceptable safety; side effects were manageable and the treatment was generally well tolerated.

Patients with the KRAS mutation saw deeper and more durable responses. While the trial was not large, the results were considered robust enough given the unmet need in this disease to justify accelerated approval under FDA’s regulatory framework.

Clinical Importance

This approval changes the landscape for LGSOC. Where treatments have often been borrowed from other ovarian cancer types, or simply exhausted without achieving durable responses, the availability of a therapy that specifically addresses a molecular driver (KRAS mutation) is a meaningful advance.

For clinicians this means new considerations in patient testing: identifying KRAS status becomes more important, since the mutation determines whether a patient is likely to benefit. Tumor molecular profiling may become more standard in LGSOC to guide targeted therapy decisions.

It also offers hope to patients who have had few options. For those who have already received systemic therapy, this approval introduces a therapy that has shown efficacy where chemotherapy alone often fails.

Remaining Questions

Even though the approval is welcome, it comes as a reminder that several uncertainties remain. It is not yet clear how long responses will last in broader populations and whether this therapy will improve overall survival or quality of life in the long run. Larger trials or real-world data will be needed to confirm how durable the benefit is.

Safety in longer follow up is another open question. While no unexpected safety signals emerged in the trial, accelerated approval often means post-marketing monitoring will be especially important. Side effect profiles over time, especially in patients with comorbidities, will need careful tracking.

Lastly, access and cost will matter. As with many newly approved oncology therapies, how quickly this will become available to patients in practice—and under what reimbursement terms—will affect its impact.

Overall this approval marks a turning point for LGSOC with KRAS mutation. It is a much needed targeted therapy in a cancer subtype with limited options. For clinical researchers the case underscores how molecular stratification and trial design aimed at specific genetic alterations are increasingly essential.