ASCO 2025: Real-World Outcomes of Frontline ICI Therapy in BRAF-Mutated Melanoma in the Community Setting

The emergence of immune checkpoint inhibitors (ICIs) has significantly improved outcomes for patients with advanced melanoma, including those with BRAF mutations who are at heightened risk for developing melanoma brain metastases (MBM). Yet, real-world evidence remains limited on how MBM impacts clinical outcomes among these patients—especially outside of academic centers.

Melanoma in situ. Image Credit: © David A Litman - stock.adobe.com

In a study presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois, Janet Espirito, PharmD, senior medical director at Ontada, and colleagues analyzed real-world clinical outcomes from a retrospective cohort of 757 patients with BRAF-mutated metastatic melanoma who initiated frontline ICI therapy between 2016 and 2022 in community oncology practices across the United States.

Using structured electronic health record (HER) and genomic testing data from The US Oncology Network and non-Network practices, the study assessed overall survival, real-world time to treatment discontinuation (TTD), and time to next treatment (TTNT). Although the observed rate of documented MBM was lower than expected (10%), outcomes for patients with MBM were comparable to those without, suggesting that MBM may not negatively impact frontline ICI effectiveness in this setting. Most patients received combination therapy (nivolumab [Opdivo; Bristol Myers Squibb] plus ipilimumab [Yervoy; Bristol Myers Squibb]), and the majority had V600E mutations.

In this interview with Pharmacy Times®, Espirito discusses the rationale for focusing on community practice data, the utility and limitations of real-world end points, and how the findings could inform treatment sequencing decisions in BRAF-mutated melanoma—especially among patients with brain metastases.

Pharmacy Times: What prompted this study to be focused within the US community oncology setting, and how might outcomes differ from those in academic centers?

Janet Espirito, PharmD, is a senior medical director at Ontada.

Janet Espirito, PharmD: This was a real-world data study utilized the iKnowMed EHR database. Because iKnowMed is an oncology specific EHR used by more than 2700 providers in over 600 sites of care in community oncology settings across the US, it reflects the care of patients specifically treated in the community setting. It is not known how these outcomes differ from those in academic centers. Characteristics of patients treated at referral centers can differ from those treated in the community, so these results may not be generalizable to other settings.

Pharmacy Times: Were there notable differences in outcomes based on the type of frontline ICI regimen used, particularly between monotherapy and combination regimens?

Espirito: All patients were required to receive a frontline ICI, and combination therapy was observed to be most frequently used. Assessment of treatment patterns was performed as part of the study, though we did not stratify outcomes by monotherapy and combination therapy. This would be an opportunity for future research.

Pharmacy Times: Given the exclusion of patients with co-mutations, how might your findings differ in a more molecularly heterogeneous population?

Espirito: Little is known about the outcomes of patients with co-mutations, and the observed frequency of co-mutations in our data was small. This would also be another area of opportunity for future research.

Pharmacy Times: Can you discuss the rationale for using real-world TTD and TTNT as key end points, and how these inform clinical decision-making?

Espirito: Real world time to TTD and TTNT are often used in real world data studies as proxy indicators for duration of therapy and progression-free survival, since treatment is often discontinued or switched when there is disease progression. These real world end points do have limitations, however, as treatment can be changed or switched for other reasons as well, such as tolerability. For clinical decision making, these end points may help provide overall insights into how patients are able to remain on therapy for longer and achieve a clinical benefit.

Pharmacy Times: Did you observe any differences in treatment tolerability or adverse event–driven discontinuation among patients with or without brain metastases?

Espirito: We did not have data on reasons for treatment discontinuation as part of this study.We agree this is another valuable variable that can help provide insight into whether discontinuation is due to progression, or other reasons such as tolerability.Based on our observed findings, all cause TTD and TTNT was similar among patients with brain metastases relative to the full study population.

Pharmacy Times: How do the lower-than-expected rates of documented brain metastases in your dataset compare to clinical expectations, and could this reflect limitations in imaging or reporting in community practice?

Espirito: This study utilized only structured EHR data. A potential reason for lower than expected rates of observed brain metastases may be due to under-documentation of sites of metastases as a structured data variable. Metastatic sites are often documented in unstructured progress notes but may not be explicitly checked as a structured data element. Imaging results are also unstructured data. Thus, further assessment for this is warranted.

Pharmacy Times: What are the implications of your findings for sequencing therapy—particularly regarding when to initiate ICI vs targeted therapy in patients with BRAF mutations and asymptomatic MBM?

Espirito: Treatment selection is an individualized decision for each patient. Many factors such as disease burden, symptoms, and onset of action are important to consider when selecting therapy. Patients with active brain metastases are also often excluded from clinical trials, so outcomes in these patients are not always known. This study provides real-world evidence on outcomes among patients with BRAF mutant melanoma brain metastases who received first-line ICI therapy.