For the first time this study revealed Chinese CINV status, the prevalence of GCCP in the real clinical setting and the association between GCCP and CR rate. The findings in this study indicate that CR rate in the patients treated with GCCP beyond that seen with patients treated with GICP, thus standardizing the use of antiemetics in real clinical setting is of great significance. The strengths of this study lie in many aspects. It consisted of a total of 32 large medical centers and 2964 patients from 26 provinces of China. Compared with the previous western studies[6, 7], the bigger sample size in this study provided a more robust evaluation of the benefits of GCCP. More notably, the incidence of CR after patients receiving L/mEC was compared between GCCP and GICP for the first time, as patients treated with L/mEC were not enrolled in previous western studies.
This study illustrated that current antiemetic regimens in compliance with NCCN guideline effectively control chemotherapy-induced emesis in patients receiving HEC and MEC. In an American study (INSPIRE), Gilmore et al. found, among patients treated with HEC, higher rate of no CINV in GCCP group compared with GICP group during both acute and delayed phases (49.2% vs 37.8%, P = 0.024). For the patients treated with MEC in this study, although the positive effect of GCCP on acute CR rate was not statistically significant, INSPIRE study reported that rate of no emesis in patients treated with MEC and GCCP was statistically higher than that in GICP group (91.6% vs 81.2%, P = 0.020) during the overall phase. Aapro et al. in Pan European Emesis Registry (PEER) study indicated that in Europe, the incidence of CR in GCCP was significantly higher than it was in GICP during the acute, delayed phases and overall period (OR 1.43, P = 0.027). So findings in this study support prescribing antiemetics in compliance with guidelines in the real clinical setting for patients receiving HEC, MEC as GCCP could significantly increase the incidence of CR for patients receiving HEC and MEC. Besides, for the patients receiving L/mEC, no significant difference in CR rate between GCCP and GICP was observed, indicating that excessive treatment (more than one antiemetic) for patients receiving LEC and prescribing antiemetics for patients receiving minimally emetogenic chemotherapy could not increase the incidence of CR.
In this study, only 13.6% of patients prescribed HEC and 35.7% of patients prescribed MEC complied the NCCN 2019 guidelines, respectively, which were comparable with the results reported in the conducted by Aapro et al. (11%, 39%, respectively). However, this was not a satisfactory result when compared with the GCCP prevalence in a Japanese study, in which Hirotoshi et al. reported 96% of patients receiving carboplatin-based chemotherapy (HEC and MEC were both included) were in compliance with the antiemesis guidelines based on JSCO 2010 guidelines. Except the fact of using different guidelines, Japan enacted the first cancer control law in 2006, which confirmed that political policies could influence compliance with guidelines. Economic burden is another notable issue. The cost-effectiveness of using aprepitant was reported quite good in Germany, the United States and the United Kingdom. But it has not been involved into Chinese health insurance, which might be responsible for the insufficient use of aprepitant in patients receiving HEC (only 255 out of 1184 patients receiving HEC were administered aprepitant in this survey), hence improving health care policy might be a practical measure to increase guideline consistency and reduce the burden of CINV.
The incidence of nausea during overall, acute and delayed phases was more frequent than vomiting, which was consistent with previous studies[16, 17]. Ng, T. L et al. reported that patients ranked nausea more of a problem than vomiting. The incidence of nausea during the overall phase was approximately 3.5-fold higher than that in the vomiting. This implies the control of nausea in real clinical setting was much worse compared to the control of vomiting. For the overall study population, data generated in this study found that the incidence of acute CINV was higher than the incidence of delayed CINV, unlike results reported by previous studies indicating that incidence of delayed CINV was higher[16, 20].This might because those previous studies analyzed first cycle of chemotherapy among chemotherapy-naïve patients . while our study, as a cross-sectional study, referred to patients’ most recent treatment cycle consisting of diverse chemotherapy regimens, confounding factors were inevitable. Vidall et al found the same pattern of CINV incidence as our study which might because they also referred to patients’ most recent cycle of chemotherapy. The consistency might imply the incidence of CINV in the acute phase was indeed higher compared with delayed phase in real clinical setting. Unexpectedly, higher percentage of patients receiving MEC experienced nausea compared to patients receiving HEC, although the prevalence of GCCP in MEC was higher than that in HEC. This could be attributed to the insufficient education and contacts between oncologists and patients receiving MEC, unlike the patients receiving HEC, who were more prone to be educated about the prophylaxis of CINV.
5HT3-RA was the basis of an antiemetic regimen as 97.03% of patients had 5HT3-RA in their prophylaxis antiemetic regimens. A phase III clinical study reported that among different types of 5HT3-RA, PALO as the most commonly prescribed, its complete response (CR) rates for CINV were significantly higher compared with 1st generation 5HT3-RA in the delayed and overall phases. Two large phase III trials involving patients treated with MEC showed higher rate of preventing vomiting with PALO than with ondansetron or dolasetron[23, 24]. But in our study, regarding MEC, among patients treated with guideline-consistent dual antiemetics (5HT3-RA + dexamethasone) or triple antiemetics (5HT3-RA + dexamethasone + aprepitant), PALO did not show a higher CR rate when compared with the 1st generation 5HT3-RA. The reason might because in previous clinical trials patients received single agent, while in our clinical setting, most patients received combined antiemetic regimens. Therefore, in terms of combined antiemetic regimens in the real clinical setting, selection between PALO and 1st generation 5HT3-RA needs further verification.
Regarding the patients receiving HEC, the addition of aprepitant into dual antiemetics is of great significance as triple antiemetics (5HT3-RA + dexamethasone + aprepitant) had higher CR rates in acute and overall phases compared with dual antiemetics (5HT3-RA + dexamethasone). This result was comparable with the study by Navari et al., in which they found addition of aprepitant to a standard regimen of 5HT3-RA and dexamethasone in patients receiving HEC improves the CR rate of acute CINV. Two trials involving patients receiving HEC reported significantly higher efficacy in the control of emesis with the addition of aprepitant to ondansetron plus dexamethasone than with ondansetron plus dexamethasone alone[25, 26], therefore, the efficacy and effectiveness of aprepitant were both confirmed via previous RCTs and this cross-sectional study in the real clinical setting.
This study identified several independent predictors for overall CR in accordance with previous studies— male, use of aprepitant and no ANV (anticipatory nausea and vomiting). Besides, our results indicated that GCCP, use of aprepitant,two antiemetics (versus single agent) and L/mEC (versus HEC) were the protective factors for overall CR. Differing from the widely accepted view, this study did not identify older age as the protective factor . The reason might be attributed to the median age in our study was 56 years old, which led to an age strata bias.
The main limitation of this study was the data collection was based on patients’ recall about the most recent treatment, which led to more missing records compared to the records from patients’ daily diary. Another limitation was the results in this study may not be generalized to suburban areas in China. So above-mentioned weakness could have introduced recall bias and selection bias. Besides, most patients participated in this study were not naïve to chemotherapy, as a result, there might be more confounding factors leading to CINV, such as prior experience of poorly controlled emesis, anxiety about chemotherapy. Despite above limitations, the results in this survey supported previous studies and further illustrated the positive effect of antiemetic guideline on controlling CINV.