Subgroup analyses of the safety and efficacy of ramucirumab in Japanese and Western patients in RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer

Background: FOLFIRI [irinotecan, folinic acid (CF), and fluorouracil] is considered a standard second-line chemotherapy regimen for patients with metastatic colorectal cancer (mCRC) who failed first-line XELOX/FOLFOX regimens. However, it remains unknown whether fluorouracil is still necessary in this case. This trial was designed to test the superiority of FOLFIRI over single-agent irinotecan as a second-line treatment for patients with mCRC. Methods: This randomized clinical trial was conducted in five hospitals in China. From 4 November 2016 to 17 January 2020, patients aged 18 years or older with histologically confirmed unresectable mCRC and who had failed first-line XELOX/FOLFOX regimens were screened and enrolled. Patients were randomized to receive either FOLFIRI or irinotecan. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), and toxicity. Data were analyzed on an intention-to-treat basis. Results: A total of 172 patients with mCRC were randomly treated with FOLFIRI ( n = 88) or irinotecan ( n = 84). The median PFS was 104 and 112 days (3.5 and 3.7 months) in the FOLFIRI and irinotecan groups, respectively [hazard ratio (HR) = 1.084, 95% confidence interval (CI) = 0.7911–1.485; p = 0.6094], and there was also no significant difference in OS and ORR between the two groups. The incidence of the following adverse events (AEs) was significantly higher in the FOLFIRI group than in the irinotecan group: any grade AEs including leucopenia (73.9% versus 55.4%), neutropenia (72.7% versus 56.6%), thrombocytopenia (31.8% versus 18.1%), jaundice (18.2% versus 7.2%), mucositis (40.9% versus 14.5%), vomiting (37.5% versus 21.7%), and fever (19.3% versus 7.2%) and grade 3–4 neutropenia (47.7% versus 21.7%). Conclusion: This is the first head-to-head trial showing that single-agent irinotecan yielded PFS, OS, and ORR similar to FOLFIRI, with a more favorable toxicity profile; therefore, it might be a more favorable standard chemotherapy regimen for mCRC patients who failed first-line XELOX/FOLFOX regimens. Trial registration: This study is registered with ClinicalTrials.gov, number NCT02935764, registered 17 October 2016, https://clinicaltrials.gov/ct2/show/NCT02935764 .

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Efficacy and safety of intermittent versus continuous dosing schedule of apatinib combined with docetaxel as second-line treatment for advanced gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16018 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16018-e16018

Author(s):

Yifu He ◽

Ying Yan ◽

Gang Wang ◽

Yubei Sun ◽

Tengyun Xu ◽

...

Keyword(s):

Gastric Cancer ◽

Clinical Trial ◽

Advanced Gastric Cancer ◽

Dose Group ◽

Kinase Inhibitor ◽

Line Treatment ◽

Second Line ◽

Efficacy And Safety ◽

Dosing Schedule ◽

Continuous Dosing

e16018 Background: Apatinib, a VEGFR-2 tyrosine kinase inhibitor, is wildly used for the treatment of advanced or metastatic gastric cancer. However, dose modification and interruption are happened frequently due to poor patient conditions and treatment-related toxicity. This study was designed to explore the efficacy and safety of intermittent or continuous apatinib therapy in combination with docetaxel. Methods: This was an open-label, randomized clinical trial. Patients with advanced gastric cancer who progressed from first-line treatment were randomly assigned in a ratio of 1:1 to receive intermittent or continuous dosing schedule. In the intermittent dose group (IG), patients received oral apatinib 500 mg/d for 5 days followed by 2 days off. In the continuous dose group (CG), patients received 500 mg daily without interruption. Docetaxel 60 mg/m2 was administered intravenously to patients on Day 1 in a 21-day cycle in both groups. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall response rate (ORR), disease control rate (DCR), overall survival (OS), and the safety. Results: Between September 15, 2017 and November 30, 2020, 80 patients were screened for eligibility, of which 76 patients were randomly assigned into two groups (38 in the IG and 38 in the CG). In the IG and CG, 38 and 37 patients had ECOG PS 0-1, 16 and 19 patients had history of surgery, both 11 patients with more than 2 metastases, respectively. The baseline characteristics of the two groups were balanced. ORR in the IG was 21.05% vs 18.42% in the CG, and DCR was 60.53% vs 60.53%, respectively. Median PFS were 3.88 months (95% CI, 1.723-6.031) vs 3.98 months (95% CI, 1.055-6.896, p= 0.546), and median OS was 9 months (95% CI, 5.306-12.698) vs 9.40 months (95% CI, 5.204-13.588, p= 0.310) in two groups. The incidence of all grade adverse events (AEs) in the IG and CG were 94.7% and 92.1%, of which the most common AEs were hypertension (55.3% vs 65.8%), anemia (55.3% vs 63.2%), proteinuria (26.3% vs 31.6%), hand-foot syndrome (21.1% vs 26.3%). The incidence of grade ≥3 AEs were 36.8% and 39.5% in the IG and CG, respectively. In addition, the doses of 7 patients were reduced to the 250 mg in the IG, while that of 13 patients in the CG. Conclusions: Apatinib administered intermittently (5 days on/ 2 days off) exhibited similar efficacy to continuous schedule, while with less toxicity. Intermittent dosing schedule of apatinib may be an option for second-line treatment of patients with advanced gastric cancer. Clinical trial information: NCT03334591.

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