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.
The EXTEND trial tested the hypothesis that adding comprehensive metastasis-directed therapy (MDT) to chemotherapy would improve progression-free survival (PFS) over chemotherapy alone among patients with oligometastatic pancreatic ductal adenocarcinoma (PDAC).
EXTEND (ClinicalTrials.gov identifier: NCT03599765) is a multicenter, phase II basket trial randomly assigning patients with ≤five metastases 1:1 to MDT plus systemic therapy versus systemic therapy. Disease progression was defined by radiologic criteria (RECIST v1.1), clinical progression, or death. The primary end point was PFS in the per-protocol population, evaluated after all patients achieved at least 6 months of follow-up. Exploratory end points included systemic immune response measures.
Between March 19, 2019, and February 13, 2023, 41 patients were randomly assigned and 40 were eligible for the primary analysis of PFS (19 patients in the MDT arm; 21 patients in the control arm). At a median follow-up time of 17 months, the median PFS time was 10.3 months (95% CI, 4.6 to 14.0) in the MDT arm versus 2.5 months (95% CI, 1.7 to 5.1) in the control arm. PFS was significantly improved by the addition of MDT to systemic therapy (P = .030 for stratified log-rank test) with a hazard ratio of 0.43 (95% CI, 0.20 to 0.94). No grade ≥3 or greater adverse events related to MDT were observed. Systemic immune activation events were associated with MDT and correlated with improved PFS.
This study supports the addition of MDT to systemic therapy for patients with oligometastatic PDAC. Induction of systemic immunity is a possible mechanism of benefit. These results warrant confirmatory trials to refine treatment strategy and provide external validation.
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.
Asian study of nimotuzumab (humanized EGFR-inhibitor) + gemcitabine (gem) vs. gem alone. The overall survival (OS) was 10.9 vs. 8.5 months in favor of the combination arm. While the OS difference is small, recall that the OS in the NALIRIFOX and FOLFIRINOX studies are similar. The safety profile of nimotuzumab + gemcitabine is superior to a triplet or double cytotoxic chemotherapy combination regimen. This drug is currently not available in the USA but is approved for nasopharyngeal carcinoma in China.
You may have enrolled a patient in this trial, but it seems we may have a new first line regimen. Surprisingly toxicity simar in both arms, but there was improvement in PFS and OS (17% reduction in death) although it wasn’t statistically significant in OS.
More diarrhea with nalirifox, but more neutropenia with gem abraxane.
Somewhat disappointing as this was a negative study, however it is still an option for patients who are not candidates for mFOLFIRINOX.
Positive study for the combo of TMZ + cape vs. TMZ alone in met-pNET, confirming a regimen that is already widely used. Patients were first-line, and those with MGMT-def had a better response.
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