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

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.

Fig 1. Patient flow diagram.

MDV, Medical Data Vision; ICD-10, International Statistical Classification of Diseases and Related Health Problems, 10^th Revision; CRC, colorectal cancer; JSCCR, Japanese Society for Cancer of the Colon and Rectum; FOLFIRI, leucovorin, 5-fluorouracil, and irinotecan.

Fig 2

Treatment regimens in the first, second, and third lines for patients in the first-line population (started systemic therapy including biologics without prior evidence of early recurrence) who: a) had no anti-EGFR antibody prescription during the analysis period and were presumed to have RAS-mutant CRC, and b) had an anti-EGFR antibody prescription during the analysis period and were presumed to have RAS-wild type CRC. RAS, rat sarcoma viral oncogene homolog; CRC, colorectal cancer; BEV, bevacizumab; FOLFOX, leucovorin, 5-fluorouracil, and oxaliplatin; CAPOX, capecitabine and oxaliplatin; FOLFIRI, leucovorin, 5-fluorouracil, and irinotecan; SOX, S-1 and oxaliplatin; CAPE, capecitabine; IRIS, S-1 and irinotecan; FOLFOXIRI, leucovorin, 5-fluorouracil, oxaliplatin, and irinotecan; S-1, tegafur/gimestat/potassium otastat; 5-FU, 5-fluorouracil; UFT, uracil and tegafur; RAM, ramucirumab; FTD/TPI, trifluridine/tipiracil; AFL, aflibercept beta; REG, regorafenib; PANI, panitumumab; CET, cetuximab; IRI, irinotecan.