The impact of complete chemotherapy stop on the overall survival of patients with advanced colorectal cancer in first-line setting: A meta-analysis of randomized trials

Pereira, Allan Andresson Lima; Rego, Juliana Florinda de Mendonça; Munhoz, Rodrigo Ramela; Hoff, Paulo M.; Sasse, André Deeke; Riechelmann, Rachel P.

doi:10.3109/0284186x.2015.1044022

Cited by 18 publications

(8 citation statements)

References 39 publications

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“…Even though combination chemotherapy improves response rates and, in some cases, disease-related symptoms compared with monochemotherapy in mCRC patients, those with poor PS have not been included in trials evaluating the combination of fluoropyrimidine with either oxaliplatin or irinotecan 27 - 31 , and patients with ECOG PS ≥ 3 are systematically excluded from the main second- and third-line trials for CRC treatment 19 , 32 - 39 . We have data from patients with good PS that shows that de-escalation of chemotherapy 40 or even complete cessation of chemotherapy does not compromise OS, while it preserves quality of ife 41 . Additionally, the safety and benefits from adding BEV or anti-EGFR agents to standard chemotherapy in patients with poor ECOG PS are unknown because few patients with ECOG PS 2 and none with an ECOG PS 3-4 have been enrolled in phase III trials with these anticancer agents.…”

Section: Discussionmentioning

confidence: 99%

Treatment of patients with metastatic colorectal cancer and poor performance status: current evidence and challenges

Rocha¹,

Riechelmann²

2018

Clinics

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Patients with unresectable metastatic colorectal cancer live for a median of three years when treated with standard therapies. While the evidence guiding cancer-directed treatment of this disease comes from phase III trials that have mostly enrolled patients with good performance status, some patients present with poor clinical conditions. The best treatment for these patients remains to be determined. We performed a systematic review of the treatment outcomes of patients with metastatic colorectal cancer and poor performance status, defined as Eastern Cooperative Oncology Group performance status ≥2. Eligible articles were prospective or retrospective studies or case reports published in English, Portuguese or Spanish. We searched PubMed, EMBASE, LILACS and the Cochrane Library from onset until October 2017 using specific keywords for each search. We found a total of 18 publications, mostly case reports and retrospective studies (14 articles). One was an uncontrolled prospective trial, two were observational studies and one was an individual patient meta-analysis. Although some studies suggested benefits in terms of symptomatic response with standard chemotherapy, with good safety profiles when dose-reduced regimens were administered, a true survival gain could not be demonstrated. The scientific evidence for treating metastatic colorectal cancer patients with poor performance status is scarce, and more studies evaluating treatment for this population are necessary since this condition is not uncommon in clinical practice, particularly in the public healthcare system and developing countries and among destitute populations.

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Section: Discussionmentioning

confidence: 99%

Treatment of patients with metastatic colorectal cancer and poor performance status: current evidence and challenges

Rocha¹,

Riechelmann²

2018

Clinics

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“…By using individual patient data, this pooled analysis distinguishes itself from study-level meta-analyses ( Berry et al , 2015 ; Pereira et al , 2015 ; Stein et al , 2016 ; Zhao et al , 2016 ). Our pooled subgroup analyses provide the best available evidence on predictors of response to fluoropyrimidine and bevacizumab maintenance treatment compared with observation thus far.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological factors influencing outcome in metastatic colorectal cancer patients treated with fluoropyrimidine and bevacizumab maintenance treatment vs observation: an individual patient data meta-analysis of two phase 3 trials

Goey

Elias

Hinke³

et al. 2017

Br J Cancer

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Background:The CAIRO3 and AIO 0207 trials demonstrated the efficacy of fluoropyrimidine plus bevacizumab (FP+Bev) maintenance treatment in metastatic colorectal cancer (mCRC) patients. In this individual patient data meta-analysis with updated follow-up, we aim to provide more precise estimates of treatment effects and to identify subgroups that benefit most from maintenance treatment or observation.Methods:In 871 patients, randomised to FP+Bev maintenance treatment or observation, we investigated whether treatment effect was modified by sex, age, performance status, response to induction treatment, primary tumour location, number of metastatic sites, disease stage and primary tumour resection, serum LDH, platelet count, CEA, and RAS/BRAF mutation status. Primary end point was time to second progression after reintroduction of the induction regimen (PFS2). Secondary end points were first progression-free survival (PFS1) and overall survival (OS).Results:At a median follow-up of 68.5 months (IQR 54.6–87.0 months), maintenance treatment was more effective compared with observation in PFS1 (HR 0.40(95% CI 0.34–0.47)) and PFS2 (HR 0.70(0.60–0.81)). No subgroups were identified that did not benefit from maintenance treatment in PFS1 and PFS2; no clinically relevant subgroup effects were observed. Regarding OS, pooled results were not significant (HR 0.91(0.78–1.05)), and the trials showed marked heterogeneity in overall treatment effect and subgroup effects.Conclusions:FP+Bev maintenance treatment is effective in all patients, regardless of the investigated subgroups.

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“…Two systematic reviews have compared the intermittent and continuous chemotherapeutic strategies for mCRC patients [20, 21]. However, the complete CFI and maintenance strategies have basic differences from those approaches.…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis comparing maintenance strategies with continuous therapy and complete chemotherapy-free interval strategies in the treatment of metastatic colorectal cancer

Zhao

Wang

et al. 2016

Oncotarget

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There is as yet no consensus as to the best choice among the three treatment options (maintenance, complete chemotherapy-free intervals [CFIs], and continuous) for metastatic colorectal cancer (CRC). We performed a meta-analysis of six trials (N = 2, 454 patients) to compare the safety and efficacy of those three treatment strategies. Maintenance appeared to offer an advantage over CFI with respect to progression-free survival (PFS) (hazard ratio [HR]: 0.53, 95% confidence interval [CI], 0.40–0.69). PFS and overall survival (OS) were comparable between the maintenance and continuous strategies (HR: 1.18, 95% CI, 0.96–1.46; HR: 1.05, 95% CI, 0.98–1.27, respectively), as was OS between the maintenance and CFI strategies (HR: 0.84; 95% CI, 0.70–1.00). The incidence of grade 3/4 toxicity, including neutropenia, neuropathy, hand-foot syndrome and fatigue, was lower with maintenance than with continuous therapy. A maintenance regimen utilizing bevacizumab-based doublets appeared to confer a slight advantage over bevacizumab monotherapy with respect to PFS (P = 0.011). Maintenance appeared to reduce cumulative grade 3/4 toxicity as compared to the continuous strategy, while showing comparable efficacy. Bevacizumab-based doublets appeared to be of particular value in patients with metastatic CRC.

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The impact of complete chemotherapy stop on the overall survival of patients with advanced colorectal cancer in first-line setting: A meta-analysis of randomized trials

Cited by 18 publications

References 39 publications

Treatment of patients with metastatic colorectal cancer and poor performance status: current evidence and challenges

Treatment of patients with metastatic colorectal cancer and poor performance status: current evidence and challenges

Clinicopathological factors influencing outcome in metastatic colorectal cancer patients treated with fluoropyrimidine and bevacizumab maintenance treatment vs observation: an individual patient data meta-analysis of two phase 3 trials

Meta-analysis comparing maintenance strategies with continuous therapy and complete chemotherapy-free interval strategies in the treatment of metastatic colorectal cancer

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