Jonathan Lee, MD, MSc

Patients facing second-line therapy for metastatic pancreatic cancer most often want to know how long they will live.

The phase 3 RASolute 302 trial randomly assigned 500 patients with metastatic pancreatic cancer and progression on 1 prior regimen to oral daraxonrasib 300 mg once daily or investigator's choice of 4 standard chemotherapy regimens.

The AZUR-1 trial builds on earlier single-institution data showing that single-agent anti-PD-1 therapy could spare select patients with mismatch repair-deficient rectal cancer from surgery and radiation.

AMPLIFY-7P evaluated a lymph node-targeting mutant KRAS amphiphile vaccine versus observation as adjuvant therapy for patients with resected pancreatic ductal adenocarcinoma.

Additional analyses from the RASolute 302 trial offer further insight into daraxonrasib, a pan-RAS inhibitor, compared with chemotherapy in patients with previously treated metastatic pancreatic adenocarcinoma.

Practice-changing ESMO 2026 GI oncology highlights, including zanidatamab-based regimens that extend survival in HER2-positive gastroesophageal cancer, even in PD-L1–negative patients.

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.

For decades, small molecules could not directly target RAS, the primary oncogenic driver of pancreatic cancer. Tanios S. Bekaii-Saab, MD, opens this discussion on metastatic pancreatic ductal adenocarcinoma by asking what changed. Anne Noonan, MB BCh, PhD, credits the 2013 discovery of a drug-binding pocket on the surface of mutant RAS, known as the switch II pocket, which enabled the first preclinical RAS inhibitors. She explains that RAS proteins cycle between an inactive guanosine diphosphate-bound off state and an active guanosine triphosphate-bound on state, and that oncogenic mutations shift this equilibrium toward the on state. Paul E. Oberstein, MD, describes the tri-complex approach: the oral drug enters the cell, binds the chaperone protein cyclophilin A, and that complex then binds active RAS to block downstream signaling, using the cell's own machinery. Shiraj Sen, MD, PhD, shares how he explains this mechanism to patients, comparing the medicine to a Trojan horse that uses a chaperone protein to reach and block RAS.

In this episode of the Moonlight Shift, Jonathan Lee, MD, and Chinmay Jani, MD, dive into the ins and outs of oncology fellowship and training.

Jonathan Wennan Lee, MD, MSc, discusses future directions for studying PD-L1 as a predictive biomarker in EGFR-mutated NSCLC.

Jonathan Wennan Lee, MD, MSc; and Ashish Saxena, MD, PhD, discuss the potential future utility of PD-L1 expression as a biomarker in EGFR-mutated NSCLC.

Jonathan Wennan Lee, MD, MSc; and Ashish Saxena, MD, PhD, discuss the future for evaluating PD-L1 expression as a biomarker in EGFR-mutated NSCLC.

Jonathan Wennan Lee, MD, MSc; and Ashish Saxena, MD, PhD, note data from a study of PD-L1 expression as a marker of response to TKIs in EGFR-mutated NSCLC.

Jonathan Wennan Lee, MD, MSc; and Ashish Saxena, MD, PhD, discuss the role for PD-L1 expression as a biomarker for treatment response in EGFR-mutant NSCLC.

Experts discuss the importance of molecular profiling and testing in managing metastatic pancreatic cancer, highlighting advancements in treatment options.

Innovative drug development for pancreatic cancer focuses on KRAS and PRMT5 inhibitors, exploring combinations with chemotherapy for enhanced treatment efficacy.

Experts discuss the impact of NCCN guidelines on pancreatic cancer treatment, highlighting new therapies and future advancements in patient care.

Experts discuss the importance of communication and patient support in managing pancreatic cancer treatment and aligning care goals with patient needs.

Experts emphasize the importance of communication and patient support in managing pancreatic cancer, focusing on aligning treatment goals with personal preferences.

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Clinicians discuss managing diarrhea and nutritional support for pancreatic cancer patients, emphasizing the importance of a comprehensive care team.

Discover how NALIRIFOX offers a promising alternative to FOLFIRINOX, enhancing treatment options and reducing toxicities for pancreatic cancer patients.

Healthcare professionals discuss effective strategies for dose reduction in cancer treatment, emphasizing patient reassurance and maintaining treatment efficacy.

Explore strategies for adjusting chemotherapy dosages based on genetic mutations, enhancing patient safety and treatment efficacy in clinical practice.

Experts discuss the importance of real-world data in pancreatic cancer treatment, highlighting its impact on patient management and survival outcomes.

Experts discuss the importance of real-world data in pancreatic cancer treatment, highlighting its impact on patient management and survival outcomes.

Experts discuss the importance of real-world data in pancreatic cancer treatment, highlighting its impact on patient management and survival outcomes.

Jonathan Lee, MD, MSc, offers his tips for interviewing for a hematology/oncology fellowship.

Experts discuss evolving treatment strategies for metastatic pancreatic cancer, comparing NALIRIFOX and FOLFIRINOX in first-line therapy decisions.

Experts discuss evolving treatment strategies for metastatic pancreatic cancer, comparing NALIRIFOX and FOLFIRINOX in first-line therapy decisions.