Second-Line Treatment and the Approved Indication

Before daraxonrasib, second-line therapy for metastatic pancreatic cancer meant more chemotherapy with overlapping toxicities. Jonathan Lee, MD, describes telling patients that response was unlikely and focusing instead on limiting tumor growth and controlling symptoms. Shiraj Sen, MD, PhD, estimates that about half of patients reach second-line therapy and emphasizes offering clinical trials at every step. Tanios S. Bekaii-Saab, MD, notes that the approved indication covers patients with at least 1 prior systemic therapy and patients who are not candidates for multiagent therapy, although every trial participant had progressed on 1 prior line. Anne Noonan, MB BCh, PhD, sees a role for frail patients; however, she urges caution in defining frailty given the side effect profile. Paul E. Oberstein, MD, hopes the drug expands the pool of treated patients and advises giving chemotherapy first when patients can receive it, because the trial sequenced chemotherapy before RAS inhibition. Dr. Lee wants real-world evidence and stresses frank conversations, since first-line data remain limited.