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28-05-2018 | Nausea and vomiting | Article

Evaluation of factors contributing to the response to fosaprepitant in a heterogeneous, moderately emetogenic chemotherapy population: an exploratory analysis of a randomized phase III trial

Journal: Supportive Care in Cancer

Authors: Cindy Weinstein, Karin Jordan, Stuart A. Green, Elber Camacho, Saleem Khanani, Elizabeth Beckford-Brathwaite, Annpey Pong, Stephen J. Noga, Bernardo L. Rapoport

Publisher: Springer Berlin Heidelberg

Abstract

Purpose

Fosaprepitant improved prevention of chemotherapy-induced nausea and vomiting (CINV) in a randomized, double-blind phase III trial (PN031). This post hoc analysis explored factors that may have influenced response.

Methods

Adult subjects (N = 1000) scheduled to receive non-anthracycline and cyclophosphamide (AC) moderately emetogenic chemotherapy (MEC) on day 1 were randomly assigned 1:1 to a single-dose, 150-mg intravenous fosaprepitant regimen or a control regimen. Both regimens included dexamethasone and ondansetron on day 1, with ondansetron continuing through day 3 in the control arm only. Complete response (CR; no vomiting and no rescue medication) rates in the acute, delayed, and overall phases (0–25, 25–120, and 0–120 h, respectively) were analyzed by chemotherapy type (carboplatin-based vs non-carboplatin-based), chemotherapy duration (single-day vs multiple-day), and baseline characteristics.

Results

Most subjects received single-day chemotherapeutic regimens (70.6%), which were mainly carboplatin-based (67.6%). CR with fosaprepitant was consistent (76–80%) during the delayed and overall phases in carboplatin-based and non-carboplatin-based subgroups and in subgroups receiving single-day or multiple-day MEC regimens. Treatment effects favored fosaprepitant for the carboplatin-based versus the non-carboplatin-based group during the delayed phase (14.1 vs 6.5%; p = 0.06), and for the single-day versus the multiple-day subgroup during the delayed (13.2 vs 3.2%; p = 0.02) and overall phases (12.8 vs 4.0%; p = 0.06).

Conclusions

This exploratory analysis confirms that single-dose fosaprepitant is effective for the prevention of CINV in subjects receiving carboplatin or non-carboplatin in both single- and multiple-day non-AC MEC chemotherapy regimens. This trial is registered at ClinicalTrials.gov, number NCT01594749.

Roila F, Molassiotis A, Herrstedt J, Aapro M, Gralla RJ, Bruera E, Clark-Snow RA, Dupuis LL, Einhorn LH, Feyer P, Hesketh PJ, Jordan K, Olver I, Rapoport BL, Roscoe J, Ruhlmann CH, Walsh D, Warr D, van der Wetering M (2016) 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients. Ann Oncol 27(suppl 5):v119–v133. https://doi.org/10.1093/annonc/mdw270 CrossRefPubMed

Jordan K, Jahn F, Aapro M (2015) Recent developments in the prevention of chemotherapy-induced nausea and vomiting (CINV): a comprehensive review. Ann Oncol 26(6):1081–1090. https://doi.org/10.1093/annonc/mdv138 CrossRefPubMed

National Comprehensive Cancer Network (2016) National Comprehensive Cancer Network guidelines for supportive care. Antiemesis. https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf. Accessed 10 Nov 2017

Jordan K, Gralla R, Jahn F, Molassiotis A (2014) International antiemetic guidelines on chemotherapy induced nausea and vomiting (CINV): content and implementation in daily routine practice. Eur J Pharmacol 722:197–202. https://doi.org/10.1016/j.ejphar.2013.09.073 CrossRefPubMed

(2017) Emend [package insert]. Whitehouse Station, NJ; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc

(2017) Emend for injection [package insert]. Whitehouse Station, NJ; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc

Weinstein C, Jordan K, Green SA, Camacho E, Khanani S, Beckford-Brathwaite E, Vallejos W, Liang LW, Noga SJ, Rapoport BL (2016) Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: results of a randomized, double-blind phase III trial. Ann Oncol 27(1):172–178. https://doi.org/10.1093/annonc/mdv482 CrossRefPubMed

Basch E, Prestrud AA, Hesketh PJ, Kris MG, Feyer PC, Somerfield MR, Chesney M, Clark-Snow RA, Flaherty AM, Freundlich B, Morrow G, Rao KV, Schwartz RN, Lyman GH (2011) Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 29(31):4189–4198. https://doi.org/10.1200/JCO.2010.34.4614 CrossRefPubMedPubMedCentral

Ito Y, Karayama M, Inui N, Kuroishi S, Nakano H, Nakamura Y, Yokomura K, Toyoshima M, Shirai T, Masuda M, Yamada T, Yasuda K, Hayakawa H, Suda T, Chida K (2014) Aprepitant in patients with advanced non-small-cell lung cancer receiving carboplatin-based chemotherapy. Lung Cancer 84(3):259–264. https://doi.org/10.1016/j.lungcan.2014.03.017 CrossRefPubMed

10.

Yahata H, Sonoda K, Kobayashi H, Shimokawa M, Ohgami I, Saito T, Ogawa S, Sakai K, Ichinoe A, Ueoka Y, Hasuo Y, Nishida M, Oishi R, Kato K (2014) Aprepitant for the prevention of chemotherapy-induced nausea and vomiting with a moderately emetogenic chemotherapy: a multicenter, placebo-controlled, double-blind, randomized study in Japanese gynecologic patients receiving paclitaxel and carboplatin. Ann Oncol 25(suppl 4):iv518 Abstract 1481PDCrossRef

11.

Hesketh PJ, Schnadig ID, Schwartzberg LS, Modiano MR, Jordan K, Arora S, Powers D, Aapro M (2016) Efficacy of the neurokinin-1 receptor antagonist rolapitant in preventing nausea and vomiting in patients receiving carboplatin-based chemotherapy. Cancer 122(15):2418–2425. https://doi.org/10.1002/cncr.30054 CrossRefPubMed

12.

Hesketh PJ, Schwartzberg LS, Modiano MR, Arora S, Poma A, Schnadig ID (2015) Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in moderately emetogenic therapy (MEC). J Clin Oncol 33(suppl):abstr 9622