Risk factors and efficacy outcomes of early-onset severe neutropenia due to paclitaxel or nanoparticle albumin-bound paclitaxel combined with ramucirumab in advanced gastric cancer: a multicenter retrospective cohort study

Yuya Hagiwara; Akio Nakasya; Toshihiko Matsumoto; Tatsuki Ikoma; Yoshiyuki Yamamoto; Yusuke Kurioka; Takao Tsuduki; Takeshi Kajiwara; Tomohiro Nishina; Natsumi Yamashita; Toshikazu Moriwaki; Ichinosuke Hyodo

doi:10.21037/jgo-22-499

Risk factors and efficacy outcomes of early-onset severe neutropenia due to paclitaxel or nanoparticle albumin-bound paclitaxel combined with ramucirumab in advanced gastric cancer: a multicenter retrospective cohort study

J Gastrointest Oncol. 2022 Dec;13(6):2769-2778. doi: 10.21037/jgo-22-499.

Authors

Affiliations

¹ Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
² Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Ehime, Japan.
³ Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan.
⁴ Department of Internal Medicine, Himeji Red Cross Hospital, Himeji, Hyogo, Japan.
⁵ Section of Cancer Prevention and Epidemiology, Clinical Research Center, National Hospital Organization Shikoku Cancer Center, Matsuyama, Ehime, Japan.

Abstract

Background: Paclitaxel or nanoparticle albumin-bound paclitaxel combined with ramucirumab (PTX/nab-PTX + RAM) is widely used as second-line chemotherapy for advanced gastric cancer (AGC), but severe neutropenia often develops with this regimen. Although previous studies have reported that severe neutropenia is a favorable prognostic factor in cancer chemotherapy, it is unclear in AGC patients receiving PTX/nab-PTX + RAM. In addition, the risk factors for early-onset of severe neutropenia (EOSN) still remain unknown.

Methods: Among patients with AGC treated with PTX/nab-PTX (on day 1, 8, and 15) + RAM (on day 1 and 15) every 4 weeks as second-line therapy from January 2017 to June 2020, those with grade 0 or 1 neutropenia before the treatment were retrospectively studied. Blood tests were performed on the day of treatment each time, and disease progression was primarily determined by computed tomography every 8±2 weeks. EOSN was defined as grade 4 neutropenia that occurred during the first 28 days. The risk factors for EOSN were investigated using multivariate logistic regression analysis. Progression-free survival (PFS) and overall survival (OS) in patients with and without EOSN were investigated using multivariate analysis with a Cox proportional hazards model.

Results: The clinical data of 244 patients were analyzed. EOSN was observed in 51 (20.9%) patients. Multivariate analysis identified the following five risk factors for EOSN: age ≥65 years [odds ratio (OR), 2.75], presence of primary tumor (OR, 2.82), presence of peritoneal metastasis (OR, 2.52), grade 1 neutropenia (OR, 3.32), and high serum level of alkaline phosphatase (OR, 2.34). The PFS was significantly longer in patients with EOSN than in those without EOSN [adjusted hazard ratio (HR), 0.61; 95% CI, 0.41-0.92] and the OS tended to be longer in patients with EOSN than in those without EOSN (adjusted HR, 0.73; 95% CI, 0.47-1.12). HR was adjusted with patient background factors and blood test data considered important as predictive or prognostic factors.

Conclusions: EOSN may be associated with favorable outcomes in patients with AGC treated with PTX/nab-PTX + RAM. We should carefully try to treat them keeping the risk factors in mind.

Keywords: Gastric cancer; neutropenia; paclitaxel; ramucirumab; risk factor.