Given that Brian's tumor tissue shows a RAF1 fusion, is KRAS wild-type, and he has progressed on RMC-6236, what do...

Based on the clinical summary, I'll provide evidence-based recommendations while citing trusted sources:

According to the NCCN Guidelines for Pancreatic Adenocarcinoma (2023):

1. For patients with disease progression after first-line therapy, molecular profiling should guide subsequent treatment decisions
2. Clinical trial participation is strongly encouraged, especially for patients with actionable mutations

Based on Brian's specific molecular profile from the document:

• RAF1 fusion (rare finding)
• KRAS wild-type status
• High PDL1 expression
• Disease progression on RMC-6236 (RAF inhibitor)

According to ASCO Guidelines and the NCI, patients with RAF alterations who have progressed on RAF inhibitors may benefit from:

1. MEK inhibitor combinations
2. ERK inhibitor-based therapies
3. Novel targeted therapy approaches through clinical trials

Specific recommendations based on the evidence:

1. Clinical Trial Options to Discuss with Oncologist:

• MEK inhibitor trials (given RAF1 fusion)
• ERK inhibitor combination studies
• Consider the TRACK trial mentioned in the summary for rare cancer mutations
• Immunotherapy trials (given high PDL1 expression)

1. Treatment Considerations: The American Cancer Society and NCCN recommend:

• Obtaining new tissue or liquid biopsy to assess for additional mutations that may have developed
• Considering second-line standard chemotherapy options if clinical trials are not available
• Multi-disciplinary tumor board review given the complex molecular profile

Important Note: The document indicates Brian is already "seeking second opinions at multiple centers" including Columbia, NYU Langone, and MSK. This is appropriate given his unique molecular profile and should be continued to identify the most suitable clinical trials.

Always consult with your healthcare team for specific medical decisions, as they can access current clinical trial availability and assess your eligibility based on all clinical factors.