NEPA (netupitant + palonosetron) Administration Is Safe and Effective in cHL Patients Receiving ABVD Regimen: A Single-Center Real Life Experience

Abstract

BACKGROUNDIn the setting of cHL, ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) is the most widely used first line chemotherapeutic treatment and it is well known that this regimen is associated with a high emetic risk (HEC). Palonosetron (PALO) currently represents one of the most effective and implemented drug for CINV prevention, but after many ABVD cycles patients (pts) frequently need to add other antiemetic drugs to obtain a good control of their symptoms. Netupitant (NETU) is the NK1-RA (neurokinin receptor antagonist) component of NEPA, the first antiemetic drug available as oral fixed combination: NETU (300mg) + PALO (0.5mg). Both ABVD drugs and NETU are metabolized by cytochrome P-450 isoform 3A4 (CYP3A4), but respect to other NK1-receptor antagonist available, NETU has demonstrated to have no clinical relevant interaction with chemotherapy drugs like etoposide, cyclophosphamide and docetaxel. However, no data are currently available about the safety profile of NETU in the setting of ABVD treatment; for that reason we started the use of this drug as salvage therapy after PALO failure.METHODSWe retrospectively analyzed the cHL pts treated with ABVD at our Center from September 2016 to January 2018. We used PALO + dexamethasone as first-line anti-CINV prophylaxis, while NEPA was introduced as salvage drug for those pts with inadequately controlled CINV.We collected data regarding demographics; diagnosis; planned chemotherapeutic treatment; performed chemotherapeutic treatment; acute, delayed and anticipatory CINV (before and after NEPA); laboratory findings including transaminases, creatinine and electrolytes (before and after NEPA); adverse reactions (before and after NEPA).The primary endpoint of the study was safety of NEPA in ABVD treated pts, while CINV control (no nausea or vomiting) was the secondary endpoint. NEPA-related safety data have been compared to the same data collected at the moment of the last previous PALO-containing regimen.RESULTSAmong the 32 pts treated with ABVD during the study period, 13 (41%) received NEPA.Three pts were males and 10 females, and median age was 33 years (range 18-61). According to disease characteristics at diagnosis the planned ABVD administrations were 12 (6 cycles) in 9 pts, 8 (4 cycles) in 3 pts and 4 (2 cycles) in 1 pt. Nine pts completed the planned chemotherapy, 1 pt skipped the last cycle for personal decision, 3 pts are ongoing treatment at the time of analysis.Reasons for shift to NEPA are as follows: acute (grade 2) CINV alone in 3/13 pts; late (grade 2) CINV alone in 3/13 pts; combined acute (4 grade 2, 1 grade 1) and late (4 grade 2, 1 grade 1) CINV in 5/13 pts; combined anticipatory (grade 1), acute (grade 1) and late (grade 2) CINV in 2/13 pts.NEPA was started after a median of 4 ABVD administrations (range 1-10). Globally 53 NEPA administrations were delivered during subsequent cycles (median number of 3 NEPA administrations for each pt, range 1-11).With regard to the primary endpoint, the observed adverse events are listed in Table 1.With regard to the secondary endpoint, anticipatory, acute and delayed CINV were detected in 15%, 77%, 77%, of PALO pts and 15%, 46% and 15% of NEPA pts, respectively (see Table 2)CONCLUSIONIn our experience NETU did not show drug-drug interaction with ABVD chemotherapy agents, and NEPA administration was globally well tolerated with mild and transient adverse events. Furthermore, in cHL ABVD treated pts who experienced nausea and/or vomiting after failure of PALO + dexamethasone antiemetic prophylaxis, NEPA has demonstrated to be effective in CINV control. In 4 out of 13 cases, after an initial improvement in CINV control, pts subsequently required to shift to anti-CINV third line treatments. On the other hand, the 9 pts who continued on NEPA administration could experience an optimal CINV control immediately after the first administration.At our knowledge no data have been published regarding NEPA toxicities in the ABVD setting. Our safety and efficacy data come from a real life experience of consecutive pts treated homogeneously at a single center and would suggest the use of NEPA as primary anti-CINV prophylaxis in previously untreated cHL pts. DisclosuresRusconi:Celgene: Research Funding.