Finally, a game changer in metastatic pancreatic ductal adenocarcinoma (mPDAC), hopefully improved access will be available soon. Daxaronasib was not only more effective than chemo in the relapsed setting, but it was also more tolerable and with a better overall quality of life.
45 patients with Non–Small-Cell Lung Cancer (NSCLC) who received the 600-mg dose, 36% had a partial response, the median progression-free survival (PFS) was 8.3 months, estimated 12-month overall survival was 59% 21 patients with metastatic pancreatic ductal adenocarcinoma 24% had a response, the median PFS was 3.0 months and the median overall survival was 10.3 months.
In this Korean retrospective review of >6MM patients, heavy ethanol consumption in patients between 20-39 years of age was associated with associated with about a 20% increased risk of pancreatic cancer. This should be taken with a grain of salt (not on your margarita) but does suggest a dose dependent effect of ethanol use and pancreatic cancer risk.
Interesting study that quantifies the risk of Venous Thromboembolism (VTE) in patients undergoing neo(adjuvant) treatment. Risk was about 9% overall, underscoring the need to be aware and potentially provide prophylaxis where appropriate.
PAXG (capecitabine 1250 mg/m² total daily dose administered as 625 mg/m² twice daily, plus intravenous cisplatin 30 mg/m², nab-paclitaxel 150 mg/m², and gemcitabine 800 mg/m² every 14 days) significantly improved event-free survival (EFS) compared with modified FOLFIRINOX (mFOLFIRINOX) in patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC) (16.0 months vs 10.2 months).
The GENERATE/JCOG1611 trial in Japanese patients with metastatic or recurrent PDAC found that neither mFOLFIRINOX nor S-IROX improved overall survival (OS) versus nab-paclitaxel/gemcitabine (median OS 14.0 vs 13.6 vs 17.0 months; hazard ratio (HR) ≈1.29), and the study was stopped early for futility. Progression-free survival (PFS) was similar across arms (≈5.8–6.7 months) but nab-paclitaxel/gemcitabine had fewer grade 3–4 GI toxicities and less febrile neutropenia, supporting its continued use in this population. The OS difference likely reflects more effective second-line sequencing after nab-paclitaxel/gemcitabine, including liposomal irinotecan, rather than intrinsic superiority. In Western studies, NALIRIFOX outperformed Nab-P/Gem, but in the Japanese trial, Nab-P/Gem remained at least as effective as triplet regimens, likely due to differences in patient population, sequencing, and access to second-line therapies.
Japanese studies, which included S-1 with oxaliplatin and irinotecan—both 5-FU–based regimens—showed no superiority to gemcitabine/nab-paclitaxel in first- or second-line therapy. The trial was terminated for futility. So, what is your regimen du jour?
I recall this trial well, in node-negative pancreatic cancer GemCap is a better option than gemcitabine alone in patients who can’t be treated with mFOLFIRINOX with improved five-year overall survival (OS) 59 vs 53%, hazard ratio (HR) 0.63.
Interesting study using local therapy in metastatic pancreatic ductal adenocarcinoma (MPDAC) patients with <=5 metastatic sites. I would really like to see overall survival data here as I think progression-free survival (PFS) is a tricky endpoint to use in a trial like this. Most likely the study arm will take a lot longer to demonstrate progression if all lesions are ablated, but most important to me is the quality of life, survival and overall exposure to cytotoxic therapy; the last of which is likely much better with local therapy being utilized.
CAR-T agent for refractory met-pancreas showing a median duration of response of 9.5 months. These treatments are far from widely available, but the proof of principle is nice to see in a disease that otherwise has not had responses to immunotherapy. Hopefully more agents to come.