A phase II study of nab-paclitaxel plus ramucirumab for the second-line treatment of patients with metastatic gastroesophageal cancer.

Abstract

365 Background: Nab-paclitaxel (NP) is a protein-stabilized formulation of paclitaxel, US FDA approved for treatment of metastatic breast cancer, advanced/metastatic non-small cell lung cancer and metastatic adenocarcinoma of the pancreas. Ramucirumab (R) is an antibody targeting vascular epithelial growth factor receptor 2 (VEGFR-2) approved for treatment of gastric or gastroesophageal (GE) adenocarcinoma in combination with paclitaxel as 2nd line treatment. This phase II study evaluated the efficacy of NP and R for pts with metastatic GE cancer. Methods: Pts with metastatic GE adenocarcinoma were treated with 125 mg/m2 NP on days 1, 8, and 15, and 8 mg/kg R on days 1 and 15 of each 28-day cycle. Pts continued study treatment (tx) until intolerable toxicity, disease progression (PD), or withdrawal of consent. Restaging occurred every 2 cycles. The primary objective was progression-free survival (PFS); secondary objectives were response rate (RR), time to progression (TTP), overall survival (OS) and toxicity. Results: 65 pts were enrolled between 05/15 and 12/18: median age 63 yrs (35-86), 75% male, 71% ECOG 1. Primary tumor sites were stomach (37%), GE junction (35%), and esophagus (28%). 83% were stage IV at initial diagnosis. 29% were HER2+ at study entry. 57% had 1st line chemo, 40% chemo + targeted agent and 3% chemo + immunotherapy. Median tx duration was 13 weeks (.1-55) for NP and 12 weeks (.1-54) for R; at data cutoff 2 pts remained on tx.60% discontinued due to PD; 17% due to AE. 43% and 23% had AE-related dose reductions of NP and R, respectively; 8% and 6% were on day 15. 58% had dose interruptions of R due to AE; 42% on day 15. Median PFS was 3.8 months (CI 95% 3.4, 4.8); median TTP 4.5 months (CI 95% 3.5, 6.3); and median OS 8.8 months (CI 95% 6.1, 11.3). RR was 15% (CI 95% 6.6, 24.2); disease control rate was 68% (CI 95% 56.3, 79.1). Most common tx related AEs were neutropenia (55%), fatigue (40%), peripheral neuropathy (37%), anorexia and mucositis (26% each). Conclusions: There were no unexpected toxicity findings with NP and R in pts with GE cancers. Compared to historical controls, outcomes in this study were similar to those seen in the Western population of pts who received paclitaxel plus R. Clinical trial information: NCT02317991.

Retrospective cohort study of nanoparticle albumin-bound paclitaxel plus ramucirumab versus paclitaxel plus ramucirumab as second-line treatment in patients with advanced gastric cancer

“…Finally, all patients enrolled in this study were Japanese. Recently, a single-arm phase II trial of nab-PTX plus RAM for patients with AGC conducted in the United States of America suggested acceptable safety profiles [17]. These data support the results of our study for the application of this regimen to all patients, regardless of race.…”

Retrospective cohort study of nanoparticle albumin-bound paclitaxel plus ramucirumab versus paclitaxel plus ramucirumab as second-line treatment in patients with advanced gastric cancer

“…Finally, all patients enrolled in this study were Japanese. Although the indication of nab-PTX was approved not for gastric cancer but for breast cancer, non-small cell lung cancer, and adenocarcinoma of pancreas by Food and Drug Administration (FDA) and European Medicines Agency (EMA), recently, a single-arm phase II trial of nab-PTX plus RAM for patients with AGC conducted in the United States of America suggested acceptable safety profiles [18]. These data support the results of our study for the application of this regimen to all patients, regardless of race.…”

Retrospective cohort study of nanoparticle albumin-bound paclitaxel plus ramucirumab versus paclitaxel plus ramucirumab as second-line treatment in patients with advanced gastric cancer

“…Finally, all patients enrolled in this study were Japanese. Although the indication of nab-PTX was approved not for gastric cancer but for breast cancer, non-small cell lung cancer, and adenocarcinoma of pancreas by Food and Drug Administration (FDA) and European Medicines Agency (EMA), recently, a single-arm phase II trial of nab-PTX plus RAM for patients with AGC conducted in the United States of America suggested acceptable safety pro les [20]. These data support the results of our study for the application of this regimen to all patients, regardless of race.…”