2018 GI CANCERS SYMPOSIUM: Nab-Paclitaxel Plus Gemcitabine in Locally Advanced Pancreatic Cancer
Primary endpoint findings and updated results of secondary endpoints from the phase II LAPACT trial of nanoparticle albumin–bound (nab)-paclitaxel (Abraxane) plus gemcitabine in patients with locally advanced pancreatic cancer were presented by Hammel et al at the 2018 Gastrointestinal (GI) Cancers Symposium (Abstract 204).
Analysis Findings
An analysis of patients with newly diagnosed, locally advanced pancreatic cancer treated with up to 6 cycles of nab-paclitaxel plus gemcitabine as an investigational induction therapy (n = 106) found that patients had a median time to treatment failure of 8.8 months (90% confidence interval [CI] = 6.67–9.82), which exceeded the protocol-specified target of 6.6 months (primary endpoint). Secondary endpoints included evaluation of the disease control rate, overall response rate, progression-free survival, and overall survival in patients treated with a nab-paclitaxel plus gemcitabine induction therapy.
The updated analysis found a 77.6% disease control rate ≥ 16 weeks (stable disease ≥ 16 weeks = 44.9%, complete response = 0%, partial response = 32%) and 65.4% disease control rate ≥ 24 weeks (stable disease ≥ 24 weeks = 32.7%, complete response = 0%, partial response = 32%). The overall response rate was 32% (complete response = 0%, partial response = 32%), the median progression-free survival was 10.8 months (90% CI = 9.26–11.63) and 12-month estimated overall survival was 72% (90% CI = 64.5%–78.9%). One or more treatment emergent adverse event occurred in 99% of patients during induction. The most common grade ≥ 3 adverse events (≥ 10%) were neutropenia (42%), anemia (11%), and fatigue (10%).
“Pancreatic cancer remains an extremely challenging disease to treat because it is often diagnosed at the metastatic stage, and even those diagnosed with locally advanced disease typically have a poor prognosis,” said Pascal Hammel, MD, gastroenterologist/oncologist at Hôpital Beaujon in Clichy, France. “Disease control is key in our patients with locally advanced disease, as it may lead to opportunities for additional treatment interventions, including radiotherapy, or even, in some favorable cases, surgical resection. The results from this study are encouraging, as it shows that induction therapy has the potential to help us achieve disease control in these locally advanced patients.”
More About LAPACT
In this prospective, phase II trial conducted in the United States, Canada, and Europe, patients with protocol-defined locally advanced, unresectable pancreatic cancer received an induction regimen of up to six cycles of nab-paclitaxel plus gemcitabine, followed by the investigator’s choice of either (a) continuation of the nab-paclitaxel plus gemcitabine regimen, (b) treatment with chemoradiation, or (c) surgery. More than half of patients (57.5%, n = 61/106) completed the induction phase with nab-paclitaxel plus gemcitabine treatment. Forty-two percent (45/106) of patients did not complete induction treatment, and the reasons for treatment discontinuation during induction included adverse events (n = 20), progressive disease (n = 8), protocol noncompliance (n = 5), physician decision (n = 6), death (n = 2), and other reasons (n = 4).
At the time of data cutoff, 45 patients in the intent-to-treat cohort received investigator’s choice of therapy after induction: 11% (12/106) of patients continued nab-paclitaxel plus gemcitabine per the protocol; 16% (17/106) received chemoradiation; and 15% of patients (16/106) with unresectable disease at the start of the study underwent tumor resection surgery following nab-paclitaxel plus gemcitabine induction therapy. The LAPACT presentation also reported patient-reported quality-of-life findings across 29 different symptom measures using the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire (QLQ-30) questionnaires.
Other relevant grade ≥3 treatment-emergent adverse events included thrombocytopenia (7.5%), peripheral sensory neuropathy (3.8%), diarrhea (3.8%), and febrile neutropenia (3.8%). Adverse events of any grade included neutropenia (58.5%), fatigue (50%), anemia (47.2%), diarrhea (46.2%), thrombocytopenia (41.5%), peripheral sensory neuropathy (23.6%), and febrile neutropenia (3.8%).
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