Treatment sequences of patients with advanced colorectal cancer and use of second-line FOLFIRI with antiangiogenic drugs in Japan: A retrospective observational study using an administrative database.

Yoshinori Kagawa,Akitaka Makiyama,Zhihong Cai,Hironaga Satake,Eiji Shinozaki,Yongzhe Piao,Yoshinori Tanizawa

doi:10.1371/journal.pone.0246160

Abstract

The objectives were to describe treatment sequences for advanced colorectal cancer (CRC), use of second-line FOLFIRI (leucovorin, 5-fluorouracil, irinotecan) plus antiangiogenic drug (bevacizumab, ramucirumab, aflibercept beta) therapy, and the factors associated with the duration of antitumor drug treatment from second-line antiangiogenic therapy in Japan. This retrospective observational study was conducted using a Japanese hospital-based administrative database. Patients were enrolled if they started adjuvant therapy (and presumably experienced early recurrence) or first-line treatment for advanced CRC between May 2016 and July 2019, and were analysed until September 2019. Factors associated with overall treatment duration from second-line treatment with FOLFIRI plus antiangiogenic drugs were explored with multivariate Cox regression analysis. The most common first-line treatments were FOLFOX (leucovorin, 5-fluorouracil, oxaliplatin) or CAPOX (capecitabine, oxaliplatin) with bevacizumab (presumed RAS-mutant CRC) and FOLFOX with panitumumab (presumed RAS-wild type CRC). The most common second-line treatments were FOLFIRI-based. Many patients did not transition to subsequent lines of therapy. For second-line treatment, antiangiogenic drugs were prescribed more often for patients with presumed RAS-mutant CRC, right-sided CRC, and independent activities of daily living (ADL). The median duration of second-line FOLFIRI plus antiangiogenic drug treatment was 4.5 months; 66.2% of patients transitioned to third-line therapy. Low body mass index and not fully independent ADL were significantly associated with shorter overall duration of antitumor drug treatment from second-line therapy. Left-sided CRC, presumed RAS-wild type CRC, previous use of oral fluoropyrimidines and use of proteinuria qualitative tests, antihypertensives, or anticholinergics during second-line therapy were significantly associated with longer treatment. Treatment of advanced CRC in Japan is consistent with both international and Japanese guidelines, but transition rates to subsequent therapies need improvement. In addition to antitumor drug treatment, better ADL, higher body mass index, management of hypertension, and proteinuria tests were associated with continuation of sequential therapy that included antiangiogenic drugs.

Highlights

Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer-related deaths worldwide [1]
Ramucirumab was approved for second-line use (May 2016) based on the results of the international phase III RAISE trial [5], and aflibercept beta was approved for second-line use (March 2017) based on the results of a Japanese phase II trial [6] and the phase III VELOUR trial, which did not include Japanese patients [7]
The mean and median duration of second-line FOLFIRI plus antiangiogenic drug treatment were 6.7 months and 4.5 months, respectively, and 66.2% of patients transitioned to third-line therapy (Table 3)

Summary

Introduction

Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer-related deaths worldwide [1]. The number of new patients with CRC and the number of deaths attributed to CRC in Japan have continued to increase, despite the availability of new treatments and treatment modalities for CRC [2,3,4]. The Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines for treatment of CRC recommend three antiangiogenic drugs as second-line treatment for unresectable advanced or recurrent CRC [4]. Ramucirumab and aflibercept beta, are recommended only as FOLFIRI combination therapy; there are three available antiangiogenic drugs that can be chosen in combination with FOLFIRI for second-line treatment. Ramucirumab was approved for second-line use (May 2016) based on the results of the international phase III RAISE trial [5], and aflibercept beta was approved for second-line use (March 2017) based on the results of a Japanese phase II trial [6] and the phase III VELOUR trial, which did not include Japanese patients [7]

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Discussion

Conclusion