Pivotal trials in patients with a wide range of solid tumors have shown that NEPA, the first combination antiemetic, is superior to PALO in preventing CINV [17, 18], and maintained high CR rates across multiple cycles of chemotherapy, with a small but consistent numeric advantage over aprepitant plus PALO [19]. Herein, we report the safety and efficacy results of a post-hoc analysis of the subgroups of patients with lung cancer from two pivotal trials [17, 19]. In study 1 [17], patients received a cisplatin-based regimen, while in study 2 [19], patients received a regimen containing either cisplatin or carboplatin, two agents that are commonly used to treat lung cancer [7]. While cisplatin is well-established as the most highly emetogenic chemotherapeutic, carboplatin is at the high end of the MEC category, with recent antiemetic guidelines now recommending that patients receiving carboplatin be given a prophylactic triplet antiemetic combination of an NK1 RA, a 5-HT3 RA, and dexamethasone [6, 11, 12].
In this report, NEPA appears to be effective in preventing nausea and vomiting in the subgroup of patients with lung cancer. High CR rates were observed across the acute, delayed, and overall phases regardless of whether cisplatin- or carboplatin-based chemotherapy was administered. As expected, the highest CR rates were seen in the acute phases in both studies, although NEPA was also efficacious in the delayed and overall phases, with sustained efficacy demonstrated across multiple cycles. In study 1, numerically higher CR rates were observed in NEPA-treated patients with lung cancer, compared with those who received PALO, mirroring the results in the original study [17], although no formal statistical comparisons were undertaken in this subgroup analysis. Of note, in study 2 [19] the CR rates observed in cycle 1 were higher in the delayed and overall phases for lung cancer patients receiving cisplatin than those patients receiving carboplatin. These findings are somewhat surprising given the respective emetogenic potential of cisplatin and carboplatin. However, as there were no appreciable differences between the baseline characteristics or potential CINV risk factors of patients receiving cisplatin or carboplatin, it is most likely that this observation was an artefact of the small sample size.
Consistent with the CR results, high NSN rates were observed in NEPA-treated lung cancer patients receiving either carboplatin or cisplatin. In study 1, NSN rates were surprisingly similar for NEPA and PALO treatment groups across all phases. However, the lack of a difference during the delayed/overall phases (89.0 vs 88.1% for NEPA and PALO, respectively, in the delayed phase, and 87.2 and 88.1% for NEPA and PALO, respectively, in the overall phase) appeared to be due to the higher-than-expected efficacy seen with PALO rather than with NEPA, as the NSN rates for NEPA in lung cancer patients mimicked those seen in the overall study population [17], while the rates for PALO were approximately 8% higher in the lung cancer subset than in the overall study population [17]. This may simply be a function of the small sample size (N = 42) in the PALO subset.
PALO, a second-generation 5-HT3 RA, has been shown to be more effective than older 5-HT3 RAs for the control of CINV in the delayed and overall phases [20]. Included both as a component of the fixed combination NEPA, and in the aprepitant-PALO-dexamethasone reference regimen, PALO may have contributed to the high antiemetic efficacy observed in both studies.
Considering the subsets of patients with non-lung cancers, the data suggest that NEPA is at least as effective in lung cancer patients as those with other cancers. In NEPA-treated non-lung cancer patients, high rates of CR and NSN were observed, with slightly better control achieved in patients receiving carboplatin than may be anticipated.
NEPA was also well tolerated in both studies in the lung and non-lung cancer populations, with AEs typical of a population of cancer patients undergoing emetogenic chemotherapy.
Limitations to the present study include its exploratory nature, given it is a post-hoc analysis, as well as the lack of formal statistical comparisons. Recent developments in the field of CINV have led to the approval of new drugs that have been rapidly incorporated in guidelines recommendations. Due to its post-hoc nature, the comparator arms included in this subgroup analysis do not correspond with current guidelines recommendations [6, 11, 12]. Factors that preclude the ability to perform formal statistical analyses between study arms (NEPA vs PALO) and patient subgroups (lung cancer vs non-lung cancer) include (1) the limited sample size of the lung cancer population in both studies, (2) non-balanced patient demographics between the different subgroups due to the loss of patient stratification by gender for the analysis, and (3) further division of the subgroups according to the anticancer treatment received (cisplatin or carboplatin) resulting in a further reduction of the sample size.
The data reported herein are not dissimilar to results from a number of studies examining the efficacy of the aprepitant-PALO-dexamethasone triplet regimen in preventing CINV in patients with lung cancer. One study reported overall CR rates in cisplatin- (71%) and carboplatin-treated patients (86%) that are similar to those reported in the current study [21]. Two other studies evaluating the efficacy of the aprepitant-PALO-dexamethasone combination in patients with NSCLC receiving a carboplatin-based regimen [22, 23] also reported CR rates in the overall phase (83.8% [22] and 80.5% [23]) similar to those reported herein (77.2%). Finally, there is at least one report that has assessed the aprepitant-PALO-dexamethasone antiemetic triplet in lung cancer patients receiving multiple cycles of cisplatin-based chemotherapy [24]. In that study, the reported CR rates in the overall phase increased from 74.4% (cycle 1) to 78.6% (cycle 6), which are slightly lower than those reported herein, where the overall CR rate was 88.4% in cycle 1 and increased to 93.5% by cycle 4 for cisplatin-treated patients in study 2. The above-mentioned limitations of the present study may help explain the differences in the results.
In conclusion, the data from this post-hoc analysis of the subgroup of patients with lung cancer from two pivotal trials are in alignment with the results reported in the parent studies [17, 19]. NEPA, the first oral combination antiemetic, has been shown to be safe and effective in patients with lung cancer receiving platinum-based chemotherapy across the acute, delayed, and overall phases and throughout multiple cycles. As an oral treatment targeting two antiemetic pathways with a single dose administered only once per cycle, NEPA offers a convenient and simplified prophylactic option. Consequently, this drug may facilitate adherence to antiemetic guidelines and improve treatment compliance, which in turn could lead to improved CINV prevention.