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Adjuvant Nivolumab in Esophageal or Gastroesophageal Junction Cancer: the Improvement in Progression-Free Survival Is Small

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Abstract

Esophageal cancer is the seventh most common cancer globally, accounting more than a half million deaths per year. Despite several therapeutic options in neoadjuvant setting, including chemoradiotherapy and surgery, no adjuvant treatment has been established for patients at high risk of recurrence. Even so, findings from the recently published CheckMate 577 trial seem to suggest an important clinical impact, in terms of disease-free progression, for the use of adjuvant nivolumab, a PDL-1 inhibitor, in resected esophageal cancer or gastroesophageal junction cancer. The authors reported a benefit for the treatment arm of 22.4 months compared with 11.0 in the placebo group. Although median is commonly used as an endpoint in survival studies, it can be influenced by the timing of a few events in the descending portion of the Kaplan–Meier curve. Restricted mean survival time (RMST) considers the entire time-course of the curve and does not assume that event risks are constant over the follow-up. This may be helpful to a more realistic interpretation of survival outcomes. In this letter, we re-analyzed the study curves of the CheckMate 577 trial by application of RMST. While confirming the disease-free progression benefits for nivolumab compared with placebo (28.54 months for the treatment arms versus 22.70 for the controls), our analysis allows us to interpret the survival benefit in a more conservative manner.

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References

  1. Shah MA, Kennedy EB, Catenacci DV, Deighton DC, Goodman KA, Malhotra NK, et al. Treatment of locally advanced esophageal carcinoma: ASCO guideline. J Clin Oncol. 2020;38:2677–94.

    Article  PubMed  Google Scholar 

  2. Lordick F, Mariette C, Haustermans K, Obermannová R, Arnold D, ESMO Guidelines Committee. Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl 5):v50–7.

    Article  CAS  PubMed  Google Scholar 

  3. Kelly RJ, Ajani JA, Kuzdzal J, Zander T, Van Cutsem E, Piessen G, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. N Engl J Med. 2021;384(13):1191–203.

    Article  CAS  PubMed  Google Scholar 

  4. Pak K, Uno H, Kim DH, Tian L, Kane RC, Takeuchi M, et al. Interpretability of cancer clinical trial results using restricted mean survival time as an alternative to the hazard ratio. JAMA Oncol. 2017;3(12):1692–6.

    Article  PubMed  Google Scholar 

  5. Messori A. The advantages of restricted mean survival time in analysing Kaplan-Meier survival curves: analysis of 55 articles published in the last 12 months. Open Science Framework, https://osf.io/bvqnk/. 2020. https://doi.org/10.17605/OSF.IO/BHQNY.

  6. Uno H, Tian L, Horiguchi M, et al. Package “survRM2”. 2020. Accessed at https://cran.r-project.org/web/packages/survRM2/survRM2.pdf on 1 March 2021.

  7. Messori A, Bartoli L, Chiumente M, Mengato D, Trippoli S. The Restricted Mean Survival Time as a Tool for Ranking Comparative Outcomes in a Narrative Review that Evaluates a Network of Randomized Trials: An Example Based on PCSK9 Inhibitors. Am J Cardiovasc Drugs. 2021 May;21(3):349-354. https://doi.org/10.1007/s40256-020-00444-8. Epub 2020 Oct 8. PMID: 33030677.

  8. Mengato D, di Spazio L, Messori A. Survival in Real-World Patients Receiving Left Ventricular Assist Devices. Ann Thorac Surg. 2022 Jan;113(1):381. https://doi.org/10.1016/j.athoracsur.2021.02.069. Epub 2021 Mar 9. PMID: 33711301.

  9. Mengato D, Chiumente M, Messori A. Performance of the restricted mean survival time in analyzing overall survival in trials studying peri-operative or neoadjuvant chemotherapy in patients with esophageal or junctional cancer (preprint). Open Science Framework, 2021. https://osf.io/vrs7p/.

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Correspondence to Daniele Mengato.

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Mengato, D., Chiumente, M. & Messori, A. Adjuvant Nivolumab in Esophageal or Gastroesophageal Junction Cancer: the Improvement in Progression-Free Survival Is Small. J Gastrointest Canc 54, 9–10 (2023). https://doi.org/10.1007/s12029-022-00804-4

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  • DOI: https://doi.org/10.1007/s12029-022-00804-4

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