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Clinical Studies

Comment on “Dexamethasone-sparing on days 2–4 with combined palonosteron, neurokinin-1 receptor antagonist, and olanzapine in cisplatin: a randomized phase III trial (SPARED Trial)”

British Journal of Cancer volume 130, pages 895–896 (2024)Cite this article

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Minatogawa et al. [1] should be commended for conducting this important trial. Antiemetic guidelines devised from the major international organizations recommend now olanzapine as a fixed part of a four-drug prophylactic regimen in the setting of highly emetogenic chemotherapy (HEC) [2, 3]. In light of this, it is clinically relevant that a four-drug regimen containing olanzapine, palonosetron, a neurokinin-1 receptor antagonist, and dexamethasone (DEX) single-dose was shown to be non-inferior to the guideline-recommended reference regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) caused by cisplatin-based HEC. Also, in the SPARED trial both patients’ global health status scores and the incidence of severe nausea were not worsened by DEX sparing beyond day 1. However, the authors failed to take into account the available evidence on the DEX sparing strategy in the cisplatin setting when interpreting the clinical implications of the study results.

Despite the SPARED trial met its primary objective to demonstrate non-inferiority of the DEX-sparing arm in terms of complete response (CR) during the delayed phase, the authors did not confirm their study hypothesis that olanzapine 5 mg could substitute for DEX on days 2–4 to prevent delayed CINV following cisplatin. This position relies on the finding that DEX sparing beyond day 1 caused a significant increase in mild to moderate nausea and appetite loss [1]. It is interesting to note that a prior non-inferiority study (LUNG-NEPA trial) showed comparable antiemetic control during the 5 days post-chemotherapy with a three-drug regimen of NEPA (a fixed-dose combination of netupitant and palonosetron) plus DEX single-dose versus the standard reference treatment with 4-day DEX in the setting of high-dose (≥70 mg/m2) cisplatin [4]. Although olanzapine was not used, efficacy results in the DEX-sparing arm are comparable to those seen in the SPARED trial not only in terms of CR rates (primary endpoint) but also rates of patients free of nausea or vomiting. While the patient population is similar between the two studies according to sex and age, only 80% of patients in the SPARED trial received cisplatin at a dose of 70 mg/m2 or greater. Since olanzapine 5 mg combined with palonosetron, aprepitant, and multiple-day DEX was shown to be better than placebo plus the same standard regimen in patients undergoing cisplatin [5], it is important to underline that we are still lacking of evidence from an adequately powered trial comparing 5 mg with 10 mg olanzapine in the CINV setting [6]. Therefore, there is a question whether olanzapine 5 mg can provide full benefit in improving control of cisplatin-induced nausea when the drug is added to a standard antiemetic regimen with DEX sparing on days 2–4. In the SPARED trial, the results of secondary endpoints suggest that the ability to improve nausea control may be jeopardized when olanzapine 5 mg is administered in combination with the DEX-sparing strategy.

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References

  1. Minatogawa H, Izawa N, Shimomura K, Arioka H, Iihara H, Sugawara M, et al. Dexamethasone-sparing on days 2–4 with combined palonosetron, neurokinin-1 receptor antagonist, and olanzapine in cisplatin: a randomized phase III trial (SPARED Trial). Br J Cancer. 2023. https://doi.org/10.1038/s41416-023-02493-7.

  2. Herrstedt J, Celio L, Hesketh PJ, Zhang L, Navari R, Chan A, et al. 2023 updated MASCC/ESMO consensus recommendations: prevention of nausea and vomiting following high-emetic-risk antineoplastic agents. Support Care Cancer. 2023;32:47.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Hesketh PJ, Kris MG, Basch E, Bohlke K, Barbour SY, Clark-Snow SA, et al. Antiemetics: ASCO guideline update. J Clin Oncol. 2020;38:2782–97.

    Article  CAS  PubMed  Google Scholar 

  4. Celio L, Cortinovis D, Cogoni AA, Cavanna L, Martelli O, Carnio S, et al. Dexamethasone-sparing regimens with oral netupitant and palonosetron for the prevention of emesis caused by high-dose cisplatin: a randomized noninferiority study. Oncologist. 2021;26:e1854–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hashimoto H, Abe M, Tokuyama O, Mizutani H, Uchitomi Y, Yamaguchi T, et al. Olanzapine 5 mg plus standard antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting (J-FORCE): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020;21:242–9.

    Article  CAS  PubMed  Google Scholar 

  6. Herrstedt J, Clark-Snow R, Ruhlmann CH, Molassiotis A, Olver I, Rapoport BL, et al. 2023 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting. ESMO Open. 2024. https://doi.org/10.1016/j.esmoopen.2023.102195.

  7. Celio L, Cortinovis D, Cogoni AA, Cavanna L, Martelli O, Carnio S, et al. Evaluating the impact of chemotherapy-induced nausea and vomiting on daily functioning in patients receiving dexamethasone-sparing antiemetic regimens with NEPA (netupitant/palonosetron) in the cisplatin setting: results from a randomized phase 3 study. BMC Cancer. 2022;22:915.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Celio L, Cortinovis D, Cogoni AA, Cavanna L, Martelli O, Carnio S, et al. Exploratory analysis of the effect of a dexamethasone-sparing regimen for prophylaxis of cisplatin-induced emesis on food intake (LUNG-NEPA study). Sci Rep. 2023;13:1257.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Medical Oncology Unit 4, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Luigi Celio & Andrea Antonuzzo

  2. Institut Multidisciplinaire d’Oncologie, Clinique de Genolier, Genolier, Switzerland

    Matti S. Aapro

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Contributions

LC, AA and MA contributed to the conceptualization of the manuscript. LC contributed to the initial draft of the manuscript. AA and MA contributed to critically review and revise the manuscript. LC, AA and MA approved the final version of the manuscript. Ethics approval and consent to participate. Not applicable.

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Correspondence to Luigi Celio.

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Competing interests

LC has received consulting fees from Italfarmaco, Berlin Chemie, and Helsinn. AA has received honoraria from Pfizer, BMS, LeoPharma, and Recordati. MA has received consulting fee from Accord Pharmaceuticals, Amgen, BMS, Celgene, Clinigen Group, Daiichi Sankyo, Eisai, Eli Lilly, Genomic Health, G1 Therapeutics, GlaxoSmithKline, Helsinn, Hospira, Johnson & Johnson, Merck, Merck Serono, Mundipharma, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, Tesaro, Teva Pharmaceuticals, and Vifor Pharma; has received honoraria from Astellas, Bayer HealthCare Pharmaceuticals, Biocon, Boeringer Ingelheim, Cephalon, Chugai Pharmaceutical, Dr Reddy’s Laboratories, Glenmark Pharmaceuticals, Ipsen, Janssen Biotech, Kyowa Kirin Group, Sanofi, and Taiho Pharmaceutical; has received grants from Amgen, Eisai, Genomic Health, Helsinn, Hospira, Novartis, Merck, Mundipharma, Pfizer, Roche, Sandoz, Tesaro, Teva Pharmaceuticals, Vifor Pharma.

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Celio, L., Antonuzzo, A. & Aapro, M.S. Comment on “Dexamethasone-sparing on days 2–4 with combined palonosteron, neurokinin-1 receptor antagonist, and olanzapine in cisplatin: a randomized phase III trial (SPARED Trial)”. Br J Cancer 130, 895–896 (2024). https://doi.org/10.1038/s41416-024-02611-z

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