scholarly journals A Review of Clinical Studies and Practical Guide for the Administration of Triplet Chemotherapy Regimens with Bevacizumab in First-line Metastatic Colorectal Cancer

2015 ◽  
Vol 11 (3) ◽  
pp. 293-308 ◽  
Author(s):  
Fotios Loupakis ◽  
Alexander Stein ◽  
Marc Ychou ◽  
Frank Hermann ◽  
Antonieta Salud ◽  
...  
2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 248-248
Author(s):  
Catherine Dunn ◽  
Lucy Gately ◽  
Jeanne Tie ◽  
Louise M. Nott ◽  
Belinda Lee ◽  
...  

248 Background: Quality indicators (QI) are essential to monitor the efficacy of cancer care and to guide quality improvement, however many are derived from ‘expert consensus’ and are not validated against outcomes. Moreover, the majority of oncological QI are defined in the surgical setting, with only a paucity of QI for the treatment of metastatic disease. We aimed to define and validate novel QI for metastatic colorectal cancer (mCRC) based on therapeutic approaches associated with a proven survival benefit. Methods: Data was analysed from TRACC, a multisite Australian registry collecting prospective demographic, tumour, treatment and outcome data for mCRC. We identified all patients diagnosed across 11 hospitals and explored variation by site with regards to patient and tumour characteristics, first-line chemotherapy administration and resection of oligometastatic disease. Log-rank testing and Kaplan-Meier curves compare overall survival (OS) between sites, and Pearson correlation was used to assess associations with each QI. Results: We examined data from 3132 patients diagnosed with mCRC between July 2009 – April 2021. Median age was 66 years (range 62 – 71 years by site), ECOG 0-1 81% (range 69 – 96% by site), and Charlson Comorbidity Index ≤2 43% (33 – 59% by site). Multivariate analysis confirmed association of known adverse prognostic factors with inferior OS (poor ECOG, right sided primary, KRAS or BRAF mutation, all p <0.05). Median OS for entire cohort was 26.2 months (95%CI 24.9 – 27.3 months), and varied by hospital site from 20.1 – 36.1 months (p<0.001). Of the QI evaluated, rate of triplet chemotherapy (FOLFOXIRI) administration (2.8 – 13.2% by site) was very strongly correlated with OS (R2 = 0.851), rate of liver resection (9.8 – 23.2% by site) was moderately correlated (R2 = 0.523), and rates of active treatment with first-line chemotherapy (63 - 90% by site) were weakly correlated (R2 = 0.209). Other proposed QI such as rates of lung metastases resection or chemotherapy administration in the elderly showed significant variation by site, but did not correlate with survival. Conclusions: There is significant variation in OS for patients with mCRC in these Australian hospitals, with major differences in treatment approaches. Treatment strategies known to improve survival outcomes, such as triplet FOLFOXIRI chemotherapy and resection of liver metastases, may be potential QI to benchmark and track quality improvement over time. Further analysis will determine the impact of baseline patient populations between sites, and to correlate these QI with other quality measures.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3593-3593
Author(s):  
Vishal Jindal ◽  
Ruby Gupta ◽  
Kamal Kant Sahu ◽  
Mandeep Singh Rahi ◽  
Michael J. Stender ◽  
...  

3593 Background: Doublet chemotherapy FOLFOX and FOLFIRI are standard for first‐line treatment of metastatic colorectal cancer (mCRC). Recently, use of triplet chemotherapy FOLFOXIRI has shown an increased anti-cancer activity but still there is uncertainty regarding first line backbone chemotherapy. Therefore, we conducted this metanalysis to determine the efficacy, safety and outcome of triplet vs doublet chemotherapy. Methods: The study protocol was published at PROSPERO (CRD42020166745) and prepared as per PRISMA guidelines. Total 10 studies were included, with sample size of 1536 participants in triplet arm and 1535 participants in doublet arm. The primary outcome is Response rate (RR) and secondary outcomes are Progression-free survival (PFS), Overall survival (OS), post chemotherapy radical (R0) surgical resection rate of metastases. Quantitative synthesis was performed using “R” statistical package. Dichotomous outcomes were summarized using odds ratio (OR) and time to event data was summarized using hazard ratio (HR). Results: A total of 678 articles were retrieved. The Medline article search gave a result of 271 article, Embase 296, the Cochrane Library 100 and Clinical tral.gov 11, when searched through April 2020. Total 10 studies were included. All the studies were randomized, open-label, multicenter study. Out of the 10 trials 5 each were phase II and phase III studies. The pooled odds ratio for RR was 1.66 (95% CI 1.42 to 1.93) and PFS was (HR, 0.70; 95% CI, 0.63–0.78) in favor of triplet chemotherapy. There was significant improvement in radical resection (R0) of metastases (OR 1.59; 95% CI, 1.27–1.98) in triplet arm. Triplet arm was also associated with increased toxicity especially neurological events 2.51(0.88-7.16), diarrhea 2.40(1.74-3.31), neutropenia, 2.23(1.71-2.90) and thrombocytopenia 1.94(1.05-3.59). Conclusions: Findings in this meta-analysis showed that FOLFOXIRI significantly improves the PFS, RR, OS, and R0 resection rate of overall metastases over the doublet chemotherapy. The incidence of fatal adverse events was found to be more in triplet chemotherapy compared to doublet therapy. Therefore, we concluded that with moderate evidence FOLFOXIRI provide clinically meaningful efficacy benefit at cost of increased toxicity.[Table: see text]


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