Raji Shameem, MD

A panelist discusses how this is an exciting time for pancreatic cancer treatment with the development of RAS inhibitors targeting KRAS mutations (present in approximately 90% of patients with metastatic pancreatic cancer, including G12D, G12V, and G12C variants), which have shown impressive response rates in later-line settings and are being evaluated in frontline trials, before concluding the Targeted Oncology discussion on the metastatic pancreatic adenocarcinoma treatment landscape.

A panelist discusses how proactive adverse event management is crucial for patients with metastatic pancreatic cancer, including using every-2-week scheduling and primary granulocyte colony-stimulating factor (G-CSF) support to reduce myelosuppression, providing extensive patient counseling about diet, hydration, and early antidiarrheal use for liposomal irinotecan-related diarrhea, and closely monitoring for cumulative neuropathy with consideration of oxaliplatin discontinuation by 3 to 4 months if responding to prevent limitations on future therapy options.

A panelist discusses how treating metastatic pancreatic cancer requires a multidisciplinary approach with early palliative care and dietitian involvement, emphasizing that for patients with good performance status, 3-drug regimens like NALIRIFOX or modified FOLFIRINOX can provide clinical responses and quality-of-life improvements even in high disease burden cases, whereas frail patients benefit from gemcitabine plus nab-paclitaxel administered every 2 weeks, and notes that age alone should not exclude patients from 3-drug regimens as the NAPOLI-3 trial included patients aged up to 85 years.

Overview of Clinical Trial Data A panelist discusses how first-line treatment recommendations are based on 3 pivotal phase 3 randomized trials: PRODIGE 4 (which established FOLFIRINOX superiority over gemcitabine with 11.1 vs 6.8 months overall survival despite higher toxicity), MPACT (showing gemcitabine plus nab-paclitaxel benefit over single-agent gemcitabine with 8.5 vs 6.7 months survival), and the recent NAPOLI-3 (demonstrating NALIRIFOX superiority over gemcitabine plus nab-paclitaxel with 11.1 vs 9.2 months overall survival in over 750 patients across 180 sites).

A panelist discusses how treatment selection for metastatic pancreatic adenocarcinoma involves evaluating multiple factors including genetic and somatic mutations (particularly homologous recombination deficiency [HRD] alterations like BRCA1/2 and PALB2, which favor platinum-based regimens), patient age and performance status, liver function status, and drug metabolism genotype testing such as dihydropyrimidine dehydrogenase (DPD) deficiency screening to avoid severe 5-FU toxicity in rare cases of homozygous variants.

A panelist discusses how first-line treatment for metastatic pancreatic cancer depends on performance status. ECOG 0-1 patients receive preferred options like FOLFIRINOX, modified FOLFIRINOX, or the newly FDA-approved NALIRIFOX regimen (which includes liposomal irinotecan for enhanced drug delivery), whereas ECOG 2 patients typically receive gemcitabine plus nab-paclitaxel, and ECOG 3 patients receive palliative care.

A panelist discusses how a man aged 82 years with good performance status presented with unexplained weight loss and abdominal pain, leading to a diagnosis of metastatic pancreatic adenocarcinoma with KRAS G12D and TP53 mutations confirmed through imaging, biopsy, and next-generation sequencing (NGS) testing.

An expert discusses how optimal sequencing of therapies remains unclear in lower-risk MDS, with emerging combination strategies and ongoing trials that may help define the best treatment approaches.

An expert discusses how real-world evidence and patient-reported outcomes support luspatercept’s clinical benefits, while highlighting the high failure rates of ESA therapy in community practice.

An expert discusses how long-term follow-up data from the COMMANDS trial demonstrated sustained superiority of luspatercept over ESAs, with an intriguing trend toward improved overall survival that warrants further investigation.

An expert discusses how the EPO-PRETAR trial results showed no significant difference in transfusion dependence between early and late ESA initiation, emphasizing that treatment timing remains an individualized decision.

An expert discusses how the treatment landscape for lower-risk MDS has evolved with multiple new options including luspatercept, imetelstat, and lenalidomide based on specific patient characteristics like ring sideroblast status and EPO levels.

An expert discusses how a 67-year-old woman with symptomatic anemia was diagnosed with lower-risk MDS and treated with luspatercept as first-line therapy.