Cancer Res Treat.  2021 Jul;53(3):703-713. 10.4143/crt.2020.805.

Optimal Maintenance Strategy for First-Line Oxaliplatin-Containing Therapy with or without Bevacizumab in Patients with Metastatic Colorectal Cancer: A Meta-Analysis

• Moriwaki T
• Gosho M
• Sugaya A
• Yamada T
• Yamamoto Y
• Hyodo I

• KMID: 2518394
• DOI: http://doi.org/10.4143/crt.2020.805

Abstract

Purpose
Maintenance therapy after oxaliplatin withdrawal is useful in patients with metastatic colorectal cancer (mCRC). This study aimed to investigate the timing of discontinuation or reintroduction of oxaliplatin and the optimal maintenance therapy regimen for survival.
Materials and Methods
PubMed and conference abstracts were searched to select phase II and III trials of first-line oxaliplatin-containing therapy with or without bevacizumab using maintenance therapy for mCRC. Correlations of median overall survival (OS) with induction therapy regimens, induction therapy duration, maintenance therapy regimens (fluoropyrimidine plus bevacizumab [FP+Bev], FP/Bev alone, and no treatment), and oxaliplatin reintroduction were investigated using correlation and weighted multivariate regression analyses.
Results
Twenty-two treatment arms were analyzed, including 2,581 patients. The maintenance therapy regimen FP+Bev showed the strongest correlation with a prolonged OS (Spearman’s partial correlation coefficient=0.42), and the other three variables correlated weakly with the OS. The maintenance therapy regimen significantly interacted with the induction chemotherapy duration (p=0.019). The predicted OS for FP+Bev crossed the lines of FP/Bev alone at 18 weeks of induction therapy, and of no treatment at 23 weeks. The corresponding OS at 12 and 27 weeks of induction therapies were 28.6 and 24.2 months for FP+Bev, 25.9 and 28.8 months for FP/Bev alone, and 20.5 and 27.5 months for no treatment.
Conclusion
The optimal maintenance therapy regimen for the OS is a continuous induction therapy as long as possible followed by FP/Bev alone and switching to FP+Bev within approximately 4 months if induction therapy is discontinued.

Keyword

Bevacizumab; Colorectal neoplasms; Fluoropyrimidine; Maintenance therapy; Meta-analysis; Oxaliplatin; Survival

Figure

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  Fig. 1 Study selection according to the PRISMA diagram. ASCO, American Society of Clinical Oncology; ESMO, European Society of Medical Oncology; PRISMA, Preferred Reporting Items for Systemic Reviews.

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  Fig. 2 Correlations between the overall survival or progression-free survival and variables: induction therapy regimen (A, B), duration of induction therapy (C, D), maintenance therapy regimen (E, F), and oxaliplatin reintroduction rate (G). The size of each circle is proportional to the sample size. The solid line indicates the estimated regression line, and the dotted line indicates the 95% confidence interval. Bev, bevacizumab; FP, fluoropyrimidine; pR, Spearman’s partial correlation coefficient; R, Spearman’s correlation coefficient.

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  Fig. 3 Relationships between observed and predicted survival times in the extra-validation treatment arms: overall survival (A) and progression-free survival (B). Predicted progression-free survival was calculated in treatment arms recommended to continue maintenance therapy until disease progression. Bev, bevacizumab; CAPOX, capecitabine and oxaliplatin; CI, confidence interval; FOLFOX, infusional 5-fluorouracil, folinic acid, and oxaliplatin; mFOLFOX, modified infusional 5-fluorouracil, folinic acid, and oxaliplatin.

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  Fig. 4 Relationships between the predicted survival time and duration of induction therapy, and maintenance therapy regimen, with maintenance therapy rate of 100%: overall survival (A) and progression-free survival (B). CI, confidence interval; FP, fluoropyrimidine.

Reference

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