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

Luigi Celio, Diego Cortinovis, Alessio Aligi Cogoni, Luigi Cavanna, Olga Martelli, Simona Carnio, Elena Collovà, Federica Bertolini, Fausto Petrelli, Alessandra Cassano, Rita Chiari, Francesca Zanelli, Salvatore Pisconti, Isabella Vittimberga, Antonietta Letizia, Andrea Misino, Angela Gernone, Erminio Bonizzoni, Sara Pilotto, Sabino De Placido, Emilio Bria, Luigi Celio, Diego Cortinovis, Alessio Aligi Cogoni, Luigi Cavanna, Olga Martelli, Simona Carnio, Elena Collovà, Federica Bertolini, Fausto Petrelli, Alessandra Cassano, Rita Chiari, Francesca Zanelli, Salvatore Pisconti, Isabella Vittimberga, Antonietta Letizia, Andrea Misino, Angela Gernone, Erminio Bonizzoni, Sara Pilotto, Sabino De Placido, Emilio Bria

Abstract

Background: The non-inferiority of dexamethasone (DEX) on day 1, with or without low-dose DEX on days 2 and 3, combined with oral NEPA (netupitant/palonosetron), compared with the guideline-consistent use of DEX was demonstrated in cisplatin. Here, we complete the analysis by assessing the impact of emesis on daily lives of patients receiving DEX-sparing regimens using the Functional Living Index-Emesis (FLIE).

Methods: Chemotherapy-naïve patients undergoing cisplatin (≥70 mg/m2), were given NEPA and DEX (12 mg) on day 1 and randomized to receive either 1) no further DEX (DEX1), 2) oral DEX (4 mg daily) on days 2-3 (DEX3), or 3) DEX (4 mg twice daily) on days 2-4 (DEX4; control). Patients completed the FLIE questionnaire on day 6 of cycle 1. Endpoints included the FLIE nausea domain, vomiting domain, and overall combined domain scores, as well as the proportion of patients with no impact on daily life (NIDL; overall score > 108). This was a protocol-planned analysis.

Results: In the DEX1 group, no significant differences were observed in the FLIE nausea score (48.9 [±1.8; SE] vs. 53.7 [±1.5]), vomiting score (56.6 [±1.4] vs. 58.7 [±0.8]) and overall score (105.6 [±2.8] vs.112.4 [±1.9]) versus DEX4 control; similar results were observed in the DEX3 group for nausea score (49.6 [±1.7]), vomiting score (58.2 [±1]) and overall score (107.8 [±2.4]) versus control. There were no significant between-group differences in the proportion of patients reporting NIDL.

Conclusion: Reducing DEX, when administered with NEPA, does not seem to adversely impact the daily functioning in patients undergoing cisplatin.

Trial registration: ClinicalTrials.gov NCT04201769 . Registration date: 17/12/2019 - Retrospectively registered.

Keywords: Chemotherapy-induced nausea and vomiting (CINV); Cisplatin; Dexamethasone; Functional living index-Emesis; NEPA; Quality of life.

Conflict of interest statement

LCe received consulting fees from Berlin-Chemie, Italfarmaco SpA and Kyowa Kirin. RC has declared speaker’s fee - advisory boards from Astrazeneca, Roche, BMS, MSD, Pfizer, and Takeda. EBo received consulting fees from Helsinn. SP received speakers’ fees from MSD, Astra-Zeneca, BMS, Boehringer Ingelheim and Roche. EBr received speakers’ and travels’ fees from MSD, AstraZeneca, Celgene, Pfizer, Helsinn, Eli-Lilly, BMS, Novartis and Roche, as well as institutional research grants from AstraZeneca and Roche. All remaining authors have declared no conflicts of interest.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
FLIE outcome assessments. a Mean FLIE overall combined score (range 18–126), b mean nausea domain score (range 9–63), c mean vomiting domain score (range 9–63). Error bars represent 95% confidence interval. Abbreviations: FLIE, Functional Living Index-Emesis; NEPA, a fixed combination of netupitant and palonosetron; DEX1, dexamethasone day 1; DEX3, dexamethasone day 1 to 3; DEX4, dexamethasone day 1 to 4
Fig. 2
Fig. 2
Percentage of patients with NIDL for FLIE overall combined score. Abbreviations: FLIE, Functional living Index-Emesis; NIDL, no impact on daily life; NEPA, a fixed combination of netupitant and palonosetron; DEX1, dexamethasone day 1; DEX3, dexamethasone day 1 to 3; DEX4, dexamethasone day 1 to 4

References

    1. Haiderali A, Menditto L, Good M, Teitelbaum A, Wegner J. Impact on daily functioning and indirect/direct costs associated with chemotherapy-induced nausea and vomiting (CINV) in a US population. Support Care Cancer. 2011;19:843–851. doi: 10.1007/s00520-010-0915-9.
    1. Bloechl-Daum B, Deuson RR, Mavros P, Hansen M, Herrstedt J. Delayed nausea and vomiting continue to reduce patients’ quality of life after highly and moderately emetogenic chemotherapy despite antiemetic treatment. J Clin Oncol. 2006;24:4472–4478. doi: 10.1200/JCO.2006.05.6382.
    1. Decker GM, DeMeyer ES, Kisko DL. Measuring the maintenance of daily life activities using the functional living index-Emesis (FLIE) in patients receiving moderately emetogenic chemotherapy. J Support Oncol. 2006;4:35–41.
    1. Karthaus M, Oskay-Ozcelik G, Wulfing P, Hielscher C, Guth D, Zahn MO, et al. Real-world evidence of NEPA, netupitant-palonosetron, in chemotherapy-induced nausea and vomiting prevention: effects on quality of life. Future Oncol. 2020;16:939–953. doi: 10.2217/fon-2020-0187.
    1. Roila F, Molassiotis A, Herrstedt J, Aapro M, Gralla RJ, Bruera E, et al. 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. 2016;27(suppl 5):v119–v133. doi: 10.1093/annonc/mdw270.
    1. Hesketh PJ, Kris MG, Basch E, Bohlke K, Barbour SY, Clark-Snow RA, et al. Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2017;35:3240–3261. doi: 10.1200/JCO.2017.74.4789.
    1. Aapro M, Molassiotis A, Dicato M, Pelaez I, Rodriguez-Lescure A, et al. The effect of guideline-consistent antiemetic therapy on chemotherapy-induced nausea and vomiting (CINV): the Pan European Emesis registry (PEER) Ann Oncol. 2012;23:1986–1992. doi: 10.1093/annonc/mds021.
    1. Gilmore JW, Peacock NW, Gu A, Szabo S, Rammage M, Sharpe J, et al. Antiemetic guideline consistency and incidence of chemotherapy-induced nausea and vomiting in US community oncology practice: INSPIRE study. J Oncol Pract. 2014;10:68–74. doi: 10.1200/JOP.2012.000816.
    1. Aapro M, Scottè F, Escobar Y, Celio L, Berman R, Franceschetti A, et al. Practice patterns for prevention of chemotherapy-induced nausea and vomiting and antiemetic guideline adherence based on real-world prescribing data. Oncologist. 2020;26:e1073–e1082. doi: 10.1002/onco.13716.
    1. Vardy J, Chiew KS, Galica J, Pond GR, Tannock IF. Side effects associated with the use of dexamethasone for prophylaxis of delayed emesis after moderately emetogenic chemotherapy. Br J Cancer. 2006;94:1011–1015. doi: 10.1038/sj.bjc.6603048.
    1. Han HS, Park JC, Park SY, Lee KT, Bae SB, Kim HJ, et al. A prospective multicenter study evaluating secondary adrenal suppression after antiemetic dexamethasone therapy in cancer patients receiving chemotherapy: a Korean south west oncology group study. Oncologist. 2015;20:1432–1439. doi: 10.1634/theoncologist.2015-0211.
    1. Nakamura M, Ishiguro A, Muranaka T, Hiraku F, Satoshi Y, Kota O, et al. A prospective observational study on effect of short-term periodic steroid premedication on bone metabolism in gastrointestinal cancer (ESPRESSO-01) Oncologist. 2017;22:592–600. doi: 10.1634/theoncologist.2016-0308.
    1. Jeong Y, Han HS, Lee HD, Yang J, Jeong J, Choi MK, et al. A pilot study evaluating steroid-induced diabetes after antiemetic dexamethasone therapy in chemotherapy-treated cancer patients. Cancer Res Treat. 2016;48:1429–1437. doi: 10.4143/crt.2015.464.
    1. Jordan K, Jahn F, Aapro M. Recent developments in the prevention of chemotherapy-induced nausea and vomiting (CINV): a comprehensive review. Ann Oncol. 2015;26:1081–1090. doi: 10.1093/annonc/mdv138.
    1. Ito Y, Tsuda T, Minatogawa H, Kano S, Sakamaki K, Ando M, et al. Placebo-controlled, double-blind phase III study comparing dexamethasone on day 1 with dexamethasone on days 1 to 3 with combined neurokinin-1 receptor antagonist and palonosetron in high-emetogenic chemotherapy. J Clin Oncol. 2018;36:1000–1006. doi: 10.1200/JCO.2017.74.4375.
    1. Celio L, Bonizzoni E, Zattarin E, Codega P, de Braud F, Aapro M. Impact of dexamethasone-sparing regimens on delayed nausea caused by moderately or highly emetogenic chemotherapy: a meta-analysis of randomised evidence. BMC Cancer. 2019;19:1268. doi: 10.1186/s12885-019-6454-y.
    1. 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–e1861. doi: 10.1002/onco.13851.
    1. Martin AR, Carides AD, Pearson JD, Horgan K, Elmer M, Schmidt C, et al. Functional relevance of antiemetic control: experience using the FLIE questionnaire in a randomised study of the NK-1 antagonist aprepitant. Eur J Cancer. 2003;39:1395–1401. doi: 10.1016/s0959-8049(03)00299-5.
    1. Martin AR, Pearson JD, Cai B, Elmer M, Horgan K, Lindley C. Assessing the impact of chemotherapy-induced nausea and vomiting on patients’ daily lives: a modified version of the functional living index-Emesis (FLIE) with 5-day recall. Support Care Cancer. 2003;11:522–527. doi: 10.1007/s00520-003-0482-4.
    1. Kottschade L, Novotny P, Lyss A, Mazurczak M, Loprinzi C, Barton D. Chemotherapy-induced nausea and vomiting: incidence and characteristics of persistent symptoms and future directions NCCTG N08C3 (Alliance) Support Care Cancer. 2016;24:2661–2667. doi: 10.1007/s00520-016-3080-y.
    1. Bosnjak SM, Gralla RJ, Schwartzberg L. Prevention of chemotherapy-induced nausea: the role of neurokinin-1 (NK1) receptor antagonists. Support Care Cancer. 2017;25:1661–1671. doi: 10.1007/s00520-017-3585-z.
    1. Fernandez-Ortega P, Caloto MT, Chirveches E, Marquilles R, San Francisco J, Quesada A, et al. Chemotherapy-induced nausea and vomiting in clinical practice: impact on patients’ quality of life. Support Care Cancer. 2012;20:3141–3148. doi: 10.1007/s00520-012-1448-1.
    1. 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;21:242–249. doi: 10.1016/S1470-2045(19)30678-3.
    1. Minatogawa H, Izawa N, Kawaguchi T, Miyaji T, Shimomura K, Kazunori H, et al. Study protocol for SPARED trial: randomised non-inferiority phase III trial comparing dexamethasone on day 1 with dexamethasone on days 1-4, combined with neurokinin-1 receptor antagonist, palonosetron and olanzapine (5 mg) in patients receiving cisplatin-based chemotherapy. BMJ Open. 2020;10:e041737. doi: 10.1136/bmjopen-2020-041737.

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