Table 2.
Second‐line immunotherapy outcomes in the pivotal RCTs, real‐world studies, and present study
| First author, year | Study design (country) | Drug | Patients, n | Age, median (range), yr | Gender: male, n (%) | PS ≥ 2, n (%) | CNS metastases, n (%) | Median PFS, mo | Median OS, mo | 1‐year OS, % |
|---|---|---|---|---|---|---|---|---|---|---|
| Brahmer, 2015 [8] | RCT, multicentric | Nivo | 135 a | 62.0 (39–85) | 111 (82.0) | 2 (1.5) | 9 (6.6) | 3.5 | 9.2 | 42.0 |
| Borghaei, 2015 [7] | RCT, multicentric | Nivo | 292 b | 61.0 (37–84) | 151 (51.7) | 0 | 34 (11.6) | 2.3 | 12.2 | 51.0 |
| Herbst, 2015 [9] | RCT, multicentric | Pem | 344 c | 63.0 (56–69) | 212 (61.6) | 3 (0.9) | 56 (16.3) | 3.9 | 10.4 | 43.2 |
| Rittmeyer, 2016 [10] | RCT, multicentric | Atezo | 425 | 63.0 (33–82) | 261 (61.4) | 0 | 85 (10.0) d | 2.8 | 13.8 | 55.0 |
| Brustugun, 2016 [41] | Observational, single center (Norway) | Nivo | 58 | 64.6 (32–88) | 28 (48.3) | 14 (24.1) | 0 | 4.0 d | 11.7 | 50.0 |
| Schouten, 2017 [42] | Observational, multicentric (Netherlands) | Nivo | 248 | 63.0 (29–84) | 136 (54.8) | 40 (16.1) | 56 (22.6) | 2.6 | 10.0 | ND |
| Dudnik, 2018 [26] | Observational, multicentric (Israel) | Nivo | 260 | 67.0 (41–99) | 176 (67.7) | 139 (53.5) | 55 (21.1) | 2.8 | 5.9 | ND |
| Manrique, 2018 [43] | Observational, multicentric (Spain) | Nivo | 188 | 58.0 (45–81) | 144 (76.6) | 19 (10.1) | 42 (22.3) | 4.8 | 12.8 | 55.0 |
| Lin, 2018 [27] | Observational, single center (Taiwan) | Nivo, Pem | 74 | 62.1 (34–87) | 43 (58.1) | 36 (48.6) | 33 (44.6) | 1.8 | 7.9 | 46.0 |
| Kobayashi, 2018 [44] | Observational, multicentric (Japan) | Nivo | 142 | 67.0(34–85) | 106 (74.6) | 23 (16.2) | 27 (19.0) | 1.9 | ND | ND |
| Geier, 2018 [45] | Observational, multicentric (France) | Nivo | 259 | 62.0 (29–85) | 187 (72.2) | 15 (5.8) | 53 (20.5) | 2.3 | 11.0 | 47.9 |
| Juergens, 2018 [46] | Observational, multicentric (Canada) | Nivo | 472 | 66.0 (36–92) | 203 (43.0) | 42 (8.9) | 62 (13.1) | 3.5 e | 12.0 | 50.0 |
| Fujimoto, 2018 [47] | Observational, multicentric (Japan) | Nivo | 613 | 66.9 (ND) | 433 (71) | 141 (23) | ND | ND | ND | 54 |
| Montana, 2018 [28] | Observational, multicentric (France) | Nivo | 98 | 65.5 (42–85) | 70 (71.4) | 39 (39.7) | ND | 1.8 | 6.3 | ND |
| Almazan, 2019 [48] | Observational, multicentric (Spain) | Nivo | 221 | 64.5 (NR) | 185 (83.7) | 30 (13.8) | 22 (10.0) | 5.3 | 9.7 | ND |
| Khozin, 2019 [49] | Observational, multicentric (U.S.) | Nivo, Pem | 1,344 f | 69.0 (61–75) | 747 (55.6) | ND | ND | ND | 8.0 | 39.0 |
| Khozin, 2019 [50] | Observational, multicentric (U.S.) | Atezo, Nivo, Pem | 5,257 g | 69.0 (62–76) | 2,819 (53.6) | ND | ND | 3.2 | 9.3 | ND |
| Ahn, 2019 [29] | Observational, single centre (Korea) | Nivo, Pem | 155 | 64.0 (35–58) | 113 (72.9) | 34 (21.9) | 61 (39.4) | 3.0 | 10.2 | ND |
| Crino, 2019 [51] | Observational, multicentric (Italy) | Nivo | 371 a | 68.0 (31–91) | 298 (80.3) | 22 (5.9) | 37 (9.9) | 4.2 | 7.9 | 39.0 |
| El Karak, 2019 [38] | Observational, (Lebanon) | Nivo, Pem | 110 | 66.0 (ND) | 75 (68.2) | ND | 17 (15.5) | 4.0 | 8.1 | ND |
| Grossi, 2019 [33] | Observational, multicentric (Italy) | Nivo | 1,588 b | 66.0 (27–89) | 1,029 (64.8) | 108 (6.8) | 409 (25.7) | 3.0 | 11.3 | 48.0 |
| Morita, 2020 [52] | Observational, multicentric (Japan) | Nivo | 901 h | 67.0 (30–90) | 651 (72.3) | 157 (17.4) | 201 (22.3) | 2.1 | 14.6 | 54.3 |
| Figueiredo, 2020 [31] | Observational, multicentric (Portugal) | Nivo | 219 | 64.0 (37–83) | 154 (70.3) | 29 (13.2) | ND | 4.9 | 13.2 | 56.5 |
| Weis, 2020 [53] | Observational, single centre (U.S.) | Atezo | 43 | 67.2 (ND) | 23 (53.5) | 9 (20.9) | ND | 2.0 | 6.5 | ND |
| Nivo | 81 | 64.3 (ND) | 39 (48.2) | 21 (28.4) | ND | 2.2 | 8.4 | ND | ||
| Martin, 2020 [37] | Observational, multicentric (Argentina) | Nivo | 109 | 65.0 (56–72) | 63 (57.8) | 17 (15.6) | ND | 6.1 | 12.1 | ND |
| Barlesi, 2020 [30] | Observational, multicentric (France) | Nivo | 1,420 i | 66.0 (35–91) | 986 (69.4) | 241 (17.1) | 282 (19.9) | 2.8 | 11.2 | 48.6 |
| Current study | Observational, single center (Slovenia) | Atezo, Nivo, Pem | 40 | 63.0 (42–77) | 20 (50.0) | 1 (3.0) | 8 (20.0) | 3.5 | 9.9 | 35.0 |
a
Only squamous cell lung cancer.
b
Only nonsquamous cell lung cancer.
c
cohort treated with pembrolizumab 2 mg/kg.
d
Reported for atezolizumab and docetaxel cohort combined.
e
Time to treatment failure.
f
227 (16.9%) patients in first line.
g
1,329 (25.3%) patients in first line.
h
38 (4.2%) patients in first line.
i
Four (0.3%) patients in first line.
Abbreviations: Atezo, atezolizumab; CNS, central nervous system; ND, no data; NR, not reached; Nivo, nivolumab; OS, overall survival; Pem, pembrolizumab; PFS, progression‐free survival; PS, performance status; RCT, randomized clinical trial.