Gemcitabine/nab-paclitaxel with pamrevlumab: A novel drug combination and trial design for the treatment of locally advanced pancreatic cancer

Vincent Picozzi, Adnan Alseidi, Jordan Winter, Michael Pishvaian, Kabir Mody, John Glaspy, Timothy Larson, Marc Matrana, Mairead Carney, Seth Porter, Elias Kouchakji, Flavio Rocha, Ewa Carrier

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Purpose Pancreatic ductal adenocarcinomas exhibit a high degree of desmoplasia due to extensive extracellular matrix deposition. Encasement of mesenteric vessels by stroma in locally advanced pancreatic cancer (LAPC) prevents surgical resection. This study sought to determine if the addition of a monoclonal antibody to connective tissue growth factor, pamrevlumab, to neoadjuvant chemotherapy would be safe and lead to improved resectability in this surgically adverse patient population. Methods In this phase I/II trial, 37 patients with LAPC were randomised 2:1 to gemcitabine/nab-paclitaxel plus (Arm A, n=24) or minus (Arm B, n=13) pamrevlumab. Those who completed six cycles of treatment were assessed for surgical eligibility by protocol-defined criteria. Resection rates, progression-free and overall survival were evaluated. Results Eighteen (75%) patients in Arm A and seven (54%) in Arm B completed six cycles of therapy with similar toxicity patterns. In Arms A and B, carbohydrate antigen 19-9 response, as defined by ≥50% decline from baseline, occurred in 13 (65%) and 5 (42%), respectively. Sixteen (16%) per cent of patients were radiographically downstaged by National Comprehensive Cancer Network criteria (5 in Arm A (21%) and 1 (8%) in Arm B). Positron emission tomography normalised in 9 (38%) vs 3 (23%) of patients in Arm A vs Arm B, respectively, and correlated with surgical exploration. Eligibility for surgical exploration was 17 (71%) vs 2 (15%) (p=0.0019) and resection was achieved in 8 (33%) vs 1 (8%) of patients in Arm A vs Arm B (p=0.1193), respectively. Postoperative complication rates were not different between arms. Conclusions Neoadjuvant chemotherapy with pamrevlumab holds promise for enhancing resection rates in patients with LAPC without added toxicity. This combination merits evaluation in a larger patient cohort.

Original languageEnglish (US)
Article numbere000668
JournalESMO Open
Volume5
Issue number4
DOIs
StatePublished - Aug 19 2020

Keywords

  • Pancreatic ductal adenocarcinoma, desmoplasia, connective tissue growth factor, monoclonal antibody

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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