Taking into account successive treatment lines in the analysis of a colorectal cancer randomised trial

Pénichoux, Juliette; Michiels, Stefan; Bouché, Olivier; Etienne, Pierre-Luc; Texereau, Patrick; Auby, Dominique; Rougier, Philippe; Ducreux, Michel; Pignon, Jean-Pierre

doi:10.1016/j.ejca.2013.02.006

Cited by 6 publications

(9 citation statements)

References 15 publications

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“…Furthermore, although our results were affected by the high percentage of patient withdrawals, other randomized trials also suffered from the same problem. 18 – 20 …”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, although our results were affected by the high percentage of patient withdrawals, other randomized trials also suffered from the same problem. [18][19][20] Another reason for caution is that the statistical analysis used, which takes into account the selection process with the IPCW method, is based on the assumed absence of unmeasured confounders. A second effect of a high percentage of patients not entering second-line treatment is a low power in estimating differential effects at second-line.…”

Section: Discussionmentioning

confidence: 99%

“…All patients provided written informed consent and the study was performed in accordance with the principles of Good Clinical Practice and the ethical standards of the Declaration of Helsinki. The protocol was approved by the local ethics committee (Comitato Etico Area Vasta Romagna) on 19…”

Section: Participantsmentioning

confidence: 99%

“…A number of studies have analyzed either first-or second-line treatment, [2][3][4][5][6][7][8][9][10][11][12][13]16,17 and only a few have collected data on more than one treatment line. [18][19][20] Their primary endpoint was mainly overall survival (OS). However, each treatment line was considered separately when progressionfree survival (PFS) was analyzed.…”

Section: Introductionmentioning

confidence: 99%

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Effectiveness of bevacizumab in first- and second-line treatment for metastatic colorectal cancer: ITACa randomized trial

et al. 2020

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Background: Cancer trials involving multiple treatment lines substantially increase our understanding of therapeutic strategies. However, even when the primary end-point of these studies is progression-free survival (PFS), their statistical analysis usually focuses on each line separately, or does not consider repeated events, thus missing potentially relevant information. Consequently, the evaluation of the effectiveness of treatment strategies is highly impaired. Methods: We evaluated the potentially different effect of bevacizumab (B) administered for the first- or second-line treatment of metastatic colorectal cancer (mCRC) in the ITACa (Italian Trial in Advanced Colorectal Cancer) randomized trial. The ITACa trial consisted of two arms: first-line chemotherapy (CT)+B followed by second-line CT alone versus first-line CT alone followed by second-line CT+B or CT+B+cetuximab according to KRAS status. Cox models for repeated disease progression were performed, and potential selection bias was adjusted using the inverse probability of censoring weighting method. Hazard ratios (HR) [95% confidence interval (CI)] for PFS (primary endpoint) were reported. Results: The overall effect of B across the two lines resulted in a HR = 0.80 (95% CI 0.68–0.95, p = 0.008). Evaluating the differential effect of B in first- and second-line, the addition of B to first-line chemotherapy (CT) produced a 10% risk reduction (HR = 0.90, 95% CI 0.72–1.12, p = 0.340) versus CT alone; B added to second-line CT produced a 36% risk reduction (HR = 0.64, 95% CI 0.49–0.84, p = 0.0011) versus CT alone. Conclusion: Our results seem to suggest that B confers a PFS advantage when administered in combination with second-line chemotherapy, which could help to improve current international guidelines on optimal sequential treatment strategies.

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“…Furthermore, although our results were affected by the high percentage of patient withdrawals, other randomized trials also suffered from the same problem. 18 – 20 …”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Participantsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effectiveness of bevacizumab in first- and second-line treatment for metastatic colorectal cancer: ITACa randomized trial

et al. 2020

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“…The FFCD 2000-05 trial [ 8 , 9 ] was a randomized trial conducted by the French Federation of Digestive Oncology, which included 410 patients with advanced colorectal cancer. It was a phase III trial comparing a sequential (S) arm to a combination (C) arm.…”

Section: Motivating Examplementioning

confidence: 99%

Evaluation of Treatment Effect with Paired Failure Times in a Single-Arm Phase II Trial in Oncology

Texier

Rotolo

Ducreux

et al. 2018

Computational and Mathematical Methods in Medicine

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In early phase clinical trials of cytotoxic drugs in oncology, the efficacy is typically evaluated based on the tumor shrinkage. However, this criterion is not always appropriate for more recent cytostatic agents, and alternative endpoints have been proposed. The growth modulation index (GMI), defined as the ratio between the times to progression in two successive treatment lines, has been proposed for a single-arm phase II trials. The treatment effect is evaluated by estimating the rate of patients having a GMI superior to a given threshold. To estimate this rate, we investigated a parametric method based on the distribution of the times to progression and a nonparametric one based on a midrank estimator. Through simulations, we studied their operating characteristics and the impact of different design parameters (censoring, dependence, and distribution) on them. In these simulations, the nonparametric estimator slightly underestimated the rate and had slightly overconservative confidence intervals in some cases. Conversely, the parametric estimator overestimated the rate and had anticonservative confidence intervals in some cases. The nonparametric method appeared to be more robust to censoring than the parametric one. In conclusion, we recommend the nonparametric method, but the parametric method can be used as a supplementary tool.

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First-line treatment in metastatic colorectal cancer: Important or crucial?

Malka

Rotolo

Boige

2017

European Journal of Cancer

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Taking into account successive treatment lines in the analysis of a colorectal cancer randomised trial

Cited by 6 publications

References 15 publications

Effectiveness of bevacizumab in first- and second-line treatment for metastatic colorectal cancer: ITACa randomized trial

Effectiveness of bevacizumab in first- and second-line treatment for metastatic colorectal cancer: ITACa randomized trial

Evaluation of Treatment Effect with Paired Failure Times in a Single-Arm Phase II Trial in Oncology

First-line treatment in metastatic colorectal cancer: Important or crucial?

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