From February 2021 to July 2021, a total of 99 patients (intention-to-treat population) were included in the study, which meant 204 CQ (larger sample than calculated). One patient in the DC group was switched to TC, receiving 3 cycles in the DC (3 CQ) and one cycle in the TC (1 CQ). Figure 1 includes an outline of the patients who were candidates to participate in the study, those who finally participated, and the CQ in each group, stratified by subgroups (type of cancer and NEPA administration timing). In the TC group, 13 patients received NEPA 1h before chemotherapy (NEPA 0) in some cycles and in other cycles, NEPA 15 minutes before it (NEPA 1). This group of patients was used to evaluate whether there were intraindividual differences in terms of CINV by changing administration time.
Fig 1. Outline of patients participating in the study and completed questionnaires stratified by subgroups: according to cancer subtype (lung, gynecologic, head and neck, and others) and time of NEPA administration (1 hour or 15 minutes before chemotherapy). Identified questionnaires means questionnaires identified by the pharmacist for eligible patients to participate in the study. Thirteen patients were counted in both subgroups (NEPA 0 and NEPA1) as they received NEPA at both administration times. DC: double combination; TC: triple combination; CQ: completed questionnaires.
Patient descriptive statistics are summarized in Table 1. Fifty-eight patients (58.6%) were female. The mean age was 66 years (46-87 years).
The subgroup of lung cancer patients included 46 patients (46.5%), 4 in DC and 42 in TC. This large difference in proportion of patients between both antiemetic regimens is explained by the fact that the change in antiemetic prophylaxis was initiated in patients with lung cancer; by the time the study was performed, many of them were already receiving TC. The gynecologic cancer subgroup, which includes ovarian, cervical, and endometrial malignancies included 36 patients (36.4%), 20 in DC and 16 in TC. The head and neck cancer subgroup, which includes mouth, esophagus, pharynx, and larynx neoplasia included 4 patients (4.0%), 2 in DC and 2 in TC. The remaining 13 patients who received carboplatin (13.1%), were included in the “others” subgroup: 8 in DC and 5 in TC.
Forty-four patients (44.4%) had stage-IV disease; 13 in DC and 32 in TC. Thirty-seven (37.4%) had stage III-disease; 17 in DC and 20 in TC. Fifty-eight CQ (28.4%) were completed in cycle 2 of chemotherapy; 20 in DC and 38 in TC, followed in frequency by cycle 1, with 43 (21.1%) CQ; 6 in DC and 37 in TC.
Table 1
Demographic and clinical characteristics of the two groups of patients: DC and TC. DC: double combination; TC: triple combination; CQ: completed questionnaires.
Characteristic
|
Intention-to-treat-population
|
|
DC (ONDA + DEX)
|
TC (NEPA+ DEX)
|
Age in years (mean ± SD)
|
66 ± 12
|
67 ± 10
|
Sex (M/F) – n patients (%)
|
11/23 (32.4 / 67.6)
|
30/35 (46.2 / 53.8)
|
Cancer type – n patients (%)
|
|
|
Lung
|
4 (11.8)
|
42 (64.6)
|
Gynecological
|
20 (58.8)
|
16 (24.6)
|
Head and neck
|
2 (5.9)
|
2 (3.1)
|
Others
|
8 (23.5)
|
5 (7.7)
|
Cancer stage - n patients (%)
|
|
|
III
|
17 (50)
|
20 (30.8)
|
IV
|
13 (38.2)
|
32 (49.2)
|
Other
|
4 (11.8)
|
13 (20)
|
Chemotherapy cycles – n CQ (%)
|
|
|
I
|
6 (8)
|
37 (28.7)
|
II
|
20 (26.7)
|
38 (29.5)
|
III
|
15 (20)
|
25 (19.4)
|
IV
|
15 (20)
|
19 (14.7)
|
V
|
11 (14.7)
|
6 (4.7)
|
VI
|
8 (10.7)
|
4 (3.1)
|
As shown in Fig 2, in the acute phase (<24h), 69/75 (92%) of the CQ in DC arm vs 127/128 (99.2%) of the CQ in TC arm remained free of vomiting episodes (p=0.0109) and 54/75 (72%) of the CQ in DC arm vs 116/128 (90.6%) of the CQ in TC arm remained nausea-free (p=0.0005). In the delayed phase (120h) results also showed benefit in favor of TC: 67/74 (90.5%) of the CQ in DC arm vs 121/124 (97.6%) of the CQ in TC arm showed patients were vomits-free (p=0.042). Regarding delayed nausea, 47/74 (63.5%) of the CQ in DC arm vs 102/124 (82.3%) of the CQ in TC arm remained free of it (p=0.0031). The number of CQ was different for each phase (acute/delayed) and for each CINV (vomiting/nausea), since the statistical analysis included all the questionnaires that were completed for each analyzed item.
The results show the effectiveness of the TC combination with statistically significant difference for vomits and nausea in both phases: acute and delayed.
The results of the subgroups analysis according to cancer type (lung, gynecologic, head and neck and other) and NEPA administration timing: NEPA 0 or NEPA 1 are summarized in Table 2.
The different number of patients in each cancer type makes CINV results difficult to compare.
Table 2
Response rate and median of vomits and nausea episodes according to treatment arm: DC or TC by subgroups: according to type of cancer (lung, gynecological, head and neck and others) and time of NEPA administration (1 hour or 15 minutes before). M: median episodes of vomiting or nausea; DC: double combination; TC: triple combination; CT: chemotherapy; NEPA 0: 1 hour before chemotherapy; NEPA 1: 15 minutes before chemotherapy.
|
RESPONSE RATE OF VOMITING
|
|
DC (ONDA + DEX)
|
TC (NEPA + DEX)
|
|
Acute (24h)
|
Delayed (120h)
|
Acute (24h)
|
Delayed (120h)
|
|
No (%)
|
Yes (%)
|
M
|
No (%)
|
Yes (%)
|
M
|
No (%)
|
Yes (%)
|
M
|
No (%)
|
Yes (%)
|
M
|
Total – nº (%)
|
69(92)
|
6(8)
|
1
|
67(90.5)
|
7(9,5)
|
1.5
|
127 (99.2)
|
1(0.8)
|
1
|
121(97.6)
|
3(2.4)
|
1
|
According to type of cancer – n CQ (%)
|
|
|
|
|
|
|
|
Lung
|
4(80)
|
1(20)
|
1
|
4(80)
|
1(20)
|
1
|
82(100)
|
0(0)
|
-
|
77(96.3)
|
3(3.8)
|
1
|
Gynecological
|
47(94)
|
3(6)
|
1
|
46(93.4)
|
3 (6)
|
1
|
30(96.7)
|
1(3.2)
|
1
|
30(100)
|
0
|
-
|
Head and neck
|
1(50)
|
1(50)
|
1
|
1(50)
|
1(50)
|
1.5
|
6(100)
|
0
|
-
|
6(100)
|
0
|
-
|
Others
|
17(94.4)
|
1(5.6)
|
1
|
16(88.9)
|
2(11.1)
|
2.5
|
9(100)
|
0
|
-
|
8(100)
|
0
|
-
|
According to NEPA administration – n CQ (%)
|
|
|
|
|
|
|
|
|
NEPA 0
|
|
|
|
|
|
|
80(98.8)
|
1(1.2)
|
1
|
77(100)
|
0(0)
|
-
|
NEPA 1
|
|
|
|
|
|
47(100)
|
0(0)
|
-
|
44(93.6)
|
3(6.4)
|
1
|
|
RESPONSE RATE OF NAUSEAS
|
|
DC (ONDA + DEX)
|
TC (NEPA + DEX)
|
|
Acute (24h)
|
Delayed (120h)
|
Acute (24h)
|
Delayed (120h)
|
|
No (%)
|
Yes (%)
|
M
|
No (%)
|
Yes (%)
|
M
|
No (%)
|
Yes (%)
|
M
|
No (%)
|
Yes (%)
|
M
|
Total – nº (%)
|
54(72)
|
21(28)
|
2
|
47(63.5)
|
27(36.5)
|
3
|
116(90.6)
|
12(9.4)
|
3
|
102(82.3)
|
22(17.7)
|
3
|
According to type of cancer – n CQ (%)
|
|
|
|
|
|
|
|
Lung
|
3(60)
|
2(40)
|
1.5
|
4(80)
|
1(20)
|
2
|
75(91.5)
|
7(8.5)
|
3
|
69(86.3)
|
11(13.4)
|
3
|
Gynecological
|
38(76)
|
12(24)
|
2
|
33(67.4)
|
16(32.7)
|
3
|
27(87.1)
|
4(12.9)
|
3
|
21(70)
|
9(30)
|
3
|
Head and neck
|
0(0)
|
2(100)
|
3
|
0(0)
|
2(100)
|
1.5
|
6(100)
|
0
|
-
|
6(100)
|
0
|
-
|
Others
|
13(72.2)
|
5(27.8)
|
2
|
10(55.6)
|
8(44.4)
|
2.5
|
8(88.9)
|
1(11.1)
|
4
|
6(75)
|
2(25)
|
4.5
|
According to NEPA administration – n CQ (%)
|
|
|
|
|
|
|
|
NEPA 0
|
|
|
|
|
|
|
76(93.8)
|
5(6.2)
|
4
|
64(83.1)
|
13(16.9)
|
3
|
NEPA 1
|
|
|
|
|
|
40(85.1)
|
7(14.9)
|
3
|
38(80.9)
|
9(19.1)
|
3
|
As a secondary endpoint, we compared whether there were differences between the NEPA 0 and NEPA 1 subgroups in terms of CINV. The data in Figure 3 show that none of the comparisons reached statistically significant differences, either comparing total CINV, acute and delayed phase CINV separately or nausea and vomits in each of the phases. Therefore, in view of the data, we can consider the change in NEPA administration timing from 1h to 15 minutes before chemotherapy equally effective.
In addition, an intra-patient analysis was performed, since there was a group of 13 patients who received NEPA in the 2 possible administration schedules, most of them started in the NEPA 0 subgroup and then switched to NEPA 1, except for patient 11. Figure 3E shows the development of symptomatology (vomits and nausea) of these 13 patients over time, according to the subgroup they were in.
The data from these 13 patients indicate that when a patient develops CINV, it does so regardless of the subgroup to which he or she belongs (NEPA 0 or NEPA 1) [1], and therefore regardless of the administration timing of antiemetic prophylaxis, except for patient 9 (Figure 3E), who had CINV only in the NEPA 1 subgroup.