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

ABSTRACT: 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.

SUBMITTER: Zhao L

PROVIDER: S-EPMC5078106 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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

Zhao Lei L Wang Jing J Li Huihui H Che Juanjuan J Cao Bangwei B

Oncotarget 20160501 22

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. ...[more]

PMID: 27072579

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Project description:Importance: In metastatic colorectal cancer, induction combination chemotherapy with a targeted agent is considered the mainstay of treatment. Multiple randomized clinical trials have examined different strategies of continuing cytotoxic therapy until progression compared with a period of either observation or the use of various maintenance agents. However, those randomized clinical trials have shown inconsistent efficacy results that make it challenging to draw any conclusion on which strategy is preferred. Therefore, a network meta-analysis is helpful to compare different agents across randomized clinical trials.Objective: To evaluate the comparative effectiveness of different treatment strategies for patients with metastatic colorectal cancer.Evidence review: MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for randomized clinical trials evaluating different strategies for patients with previously untreated metastatic colorectal cancer. Trials of interest included those including patients with metastatic colorectal cancer who were treated with an initial period of cytotoxic chemotherapy (with or without a biologic) and then switched to one of the following strategies: observation; maintenance with bevacizumab (Bev), fluoropyrimidine (FP), or both (FP?+?Bev); or continuing the induction regimen until progression. Outcomes of interest included overall survival (OS) and progression-free survival (PFS). The overall effect was pooled using the DerSimonian and Laird random-effects model. Network meta-analysis was conducted using a random-effects consistency model to pool evidence from direct and indirect comparisons. Agents were ranked using surface under the cumulative ranking (SUCRA) probabilities. Higher SUCRA scores correspond to greater efficacy. Initial analysis was performed on December 18, 2018. An updated search was performed in April 2019, and no additional studies were added.Findings: Twelve trials at low risk of bias (5540 patients; age range, 23-85 years; 64.4 % male) were included. Network meta-analysis showed no benefit of continuing full cytotoxic chemotherapy until progression vs observation in terms of PFS (hazard ratio, 0.71; 95% CI, 0.46-1.09) and OS (hazard ratio, 0.95; 95% CI, 0.85-1.07). Compared with observation, maintenance therapy showed a PFS benefit (hazard ratio, 0.58; 95% CI, 0.43-0.77) but not an OS benefit (hazard ratio, 0.91; 95% CI, 0.83-1.01). All maintenance strategies (FP, FP?+?Bev, and Bev) showed significant improvement in PFS vs observation. On SUCRA analysis, maintenance treatment (FP or FP?+?Bev) had the highest likelihood of achieving improved PFS (67.1% for FP, 99.8% for FP?+?Bev, and 36.5% for Bev) and OS (81.3% for FP, 73.2% for FP?+?Bev, and 32.6% for Bev).Conclusions and relevance: For patients with metastatic colorectal cancer, there is no benefit to continuing the full induction regimen until progression, without a period of either observation or maintenance treatment. A maintenance strategy with a fluoropyrimidine, with or without the addition of bevacizumab, is preferred. However, given the lack of a clear OS benefit, shared decision-making should include observation as an acceptable alternative.

Project description:BackgroundIt has been suggested that the acute natural killer (NK) cell response to aerobic exercise might contribute to the tumor suppressor effect of regular exercise observed in preclinical studies. Moreover, because this response is modulated by exercise intensity, high-intensity intervals exercise (HIIE) might represent an interesting therapeutic approach in cancer patients. However, this immune response remains unstudied in cancer patients currently undergoing chemotherapy.ObjectiveTo characterize the acute NK cell response following a moderate-intensity continuous aerobic exercise session (MOD), and a HIIE session in metastatic cancer patients treated with chemotherapy.MethodsTwelve cancer patients (45-65 years old) underwent a MOD and a duration and work-matched HIIE trial, in a block-randomized order. Peripheral blood mononuclear cells (PBMC) were isolated before, after and 1h after each trial. NK cell subsets were enumerated using flow cytometry and complete blood counts. The surface expression of the cytotoxic NK cell (cNK; CD56dimCD16+) subset was evaluated for its expression of the differentiation markers CD57 and CD158a, the activating receptor NKG2D, the immune checkpoints TIM-3 and PD-1, and the chemokine receptors CXCR3, CXCR4 and CCR2.ResultscNK cell blood counts increased immediately following MOD (p < 0.001) and decreased back to pre-exercise values 1 h after exercise cessation (p < 0.001). The most responsive cNK cell subsets were expressing CD57, CD158a, NKG2D, TIM-3 and CXCR3. The HIIE trial elicited a similar biphasic response, without any difference between trials (all p ≥ 0.38). However, significant changes in the MFI values of CXCR4 and NKG2D were observed in the cNK cell subset following HIIE (all p ≤ 0.038), but not MOD.ConclusionIn metastatic cancer patients undergoing chemotherapy, both MOD and HIIE can elicit an acute mobilisation and egress of NK cells exhibiting phenotypic characteristics associated with high cytotoxicity and tumor homing. Future longitudinal trials are needed to determine if combining aerobic exercise training and chemotherapy will translate towards favorable immune and clinical outcomes.

Dataset Information

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

Publications

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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