Table 1.
Characteristics of the QUALITAS study patients compared to development and external validation cohort patients.
| QUALITAS [3] | Development Dataset [5] | External Validation Dataset [5] | Italian CUP [6] | RECOURSE [7] | |
|---|---|---|---|---|---|
| Total study population | 150 (100%) | 411 | 410 | 341 | 161 FTD/TPI |
| Number of deaths within 12 weeks | 25 (17%) | 124 (30%) | 89 (22%) | 60 (18%) | 22 (14%) |
| Inclusion period | 2017–2019 | 2006–2015 | 2010–2016 | 2015–2016 | 2012–2013 |
| Country | the Netherlands | Italy | Italy | Italy | Japan, USA, EU, Australia |
| Male sex | 102 (68%) | 242 (59%) | 251 (61%) | 212 (62%) | 109 (68%) |
| Age | |||||
| Mean (±SD) | 65.0 (±9.1) | NR | NR | NR | NR |
| Median (IQR) | 65 (59–72) | 66 (58–72) | 65 (55–71) | 61 (NR) | NR |
| Range | 33–86 | NR | NR | 33–81 | NR |
| <65 | 68 (45%) | NR | NR | NR | 96 (60%) |
| 65–74 | 60 (40%) | NR | NR | NR | 7 (4%) |
| ≥75 | 22 (15%) | NR | NR | NR | 58 (36%) |
| ECOG Performance Status | |||||
| 0 | 34 (23%) | 194 (47%) | 210 (51%) | 200 (59%) | 87 (54%) |
| 1 | 63 (42%) | 154 (38%) | 200 (49%) | 132 (39%) | 74 (46%) |
| 2 | 14 (9%) | 63 (15%) | 0 (0%) | 9 (2%) | 0 (0%) |
| Missing | 39 (26%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) |
| Primary tumour site | |||||
| Right-sided colon | 44 (29%) | 128 (31%) | 135 (33%) | 99 (29%) | NR |
| Left-sided colon | 54 (36%) | 156 (38%) | 179 (44%) | NR | NR |
| Rectal | 52 (35%) | 127 (31%) | 96 (23%) | NR | 68 (42%) |
| Primary tumour resection | 113 (75%) | 348 (85%) | 358 (87%) | 312 (91%) | 124 (77%) |
| Synchronous mCRC a | 98 (65%) | 292 (71%) | 272 (66%) | 209 (61%) | NR |
| Metachronous mCRC | 52 (35%) | 119 (29%) | 138 (34%) | 132 (39%) | NR |
| Molecular pathology b | |||||
| BRAF mutation | 4 (3%) | 13 (3%) | 17 (4%) | 17 (5%) | NR |
| BRAF wildtype | 108 (72%) | 219 (53%) | 224 (55%) | NR | NR |
| BRAF status unavailable | 38 (25%) | 179 (44%) | 169 (41%) | NR | NR |
| RAS mutation | 67 (45%) | 167 (41%) | 198 (49%) | 200 (59%) | NR |
| RAS wildtype | 49 (33%) | 173 (42%) | 133 (32%) | NR | NR |
| RAS status unavailable | 34 (23%) | 71 (17%) | 79 (19%) | NR | NR |
| MSI | 2 (1%) | NR | NR | 6 (2%) | NR |
| MSS | 87 (58%) | NR | NR | 172 (50% | NR |
| MS status unavailable | 61 (41%) | NR | NR | 163 (48%) | NR |
| Number of metastatic sites | |||||
| No distant metastasis | 1 (0.7%) | 0 (0%) | 0 (0%) | 0 (0%) | NR |
| 1 organ | 20 (13%) | 87 (21%) | 81 (20%) | 14 (4%) | NR |
| 2 organs | 57 (38%) | 172 (42%) | 147 (36%) | 64 (19%) | NR |
| 3 organs | 48 (32%) | NR | NR | 122 (36%) | NR |
| ≥3 organs | 72 (48%) | 152 (37%) | 182 (44%) | 263 (77%) | NR |
| ≥4 organs | 24 (16%) | NR | NR | 141 (41%) | NR |
| Localization of metastases | |||||
| Liver | 115 (77%) | 313 (76%) | 308 (75%) | 267 (78%) | NR |
| Liver only | 10 (7%) | NR | NR | 12 (4%) | NR |
| Lung | 102 (68%) | 258 (63%) | 254 (62%) | 255 (75%) | NR |
| Lung only | 6 (4%) | NR | NR | NR | NR |
| Peritoneal | 31 (21%) | 95 (23%) | 102 (25%) | 82 (24%) | 30 (19%) |
| Peritoneal only | 4 (3%) | NR | NR | NR | NR |
| Bone | 28 (19%) | 36 (9%) | 29 (7%) | NR | NR |
| Brain | 3 (2%) | 10 (2%) | 11 (3%) | 10 (3%) | NR |
| No. of prior systemic treatment regimens | |||||
| Median (range) | NR | 3 (1–7) | 3 (1–9) | NR | NR |
| 0 | 1 (1%) | 0 (0%) | 0 (0%) | 0 (0%) | NR |
| 1 | 18 (12%) | NR | NR | 21 (6%) | NR |
| 2 | 76 (51%) | NR | NR | 93 (27%) | NR |
| 3 | 41 (27%) | NR | NR | 96 (28%) | NR |
| 4 | 14 (9%) | NR | NR | 78 (23%) | NR |
| 5 | 0 (0%) | NR | NR | 31 (9%) | NR |
| 6 | 0 (0%) | NR | NR | 18 (5%) | NR |
| ≥7 | 0 (0%) | NR | NR | 4 (1%) | NR |
| FTD/TPI-treated patients | 150 (100%) | 27 (6.6%) | 100 (24%) | 341 (100%) | 161 (100%) |
| Regorafenib-treated patients | 0 (0%) | 113 (27%) | 91 (22%) | NR | NR |
| Exposure to prior systemic anticancer agents | |||||
| fluoropyrimidine | 150 (100%) | NR | NR | 337 (99%) | 161 (100%) |
| irinotecan | 82 (55%) | NR | NR | 334 (98%) | 161 (100%) |
| oxaliplatin | 132 (88%) | NR | NR | 312 (91%) | 161 (100%) |
| bevacizumab | 95 (63%) | NR | NR | 294 (86%) | NR |
| aflibercept | 0 (0%) | NR | NR | 31 (9%) | NR |
| anti-EGFR | 47 (31%) | NR | NR | 143 (42%) | NR |
| regorafenib | 0 (0%) | NR | NR | 121 (35%) | NR |
| Exposure to treatments: | |||||
| Standard chemotherapy agents c | 75 (50%) | NR | NR | NR | 161 (100%) |
| Standard chemotherapy agents c + bevacizumab | 55 (37%) | NR | NR | NR | NR |
| Time from diagnosis mCRC to start FTD/TPI (months) | |||||
| Median (IQR) | 26.2 (16.8–40.8) | 19 (13–29) d | 26 (17–40) d | NR | NR |
| <18 months | 43 (29%) | NR | NR | 90 (26%) | NR |
| ≥18 months | 107 (71%) | NR | NR | 248 (73%) | NR |
| CEA (ng/mL) | |||||
| Median (IQR) | 46 (16–259) | 42 (7–190) | 58 (15–252) | NR | NR |
| Mean (SD) | 427 | NR | NR | NR | NR |
| Missing | 10 (7%) | NR | NR | NR | NR |
| Leucocytes (/μL) | |||||
| <10.000 | 122 (81%) | 345 (84%) | 336 (82%) | NR | NR |
| ≥10.000 | 21 (14%) | 66 (16%) | 74 (18%) | NR | NR |
| Missing | 7 (5%) | 0 (0%) | 0 (0%) | NR | NR |
| Lactate dehydrogenase (U/L) | |||||
| Median (IQR) | 272 (210–391) | 271 (191–480) | 353 (215–529) | NR | 351 (245–561) |
| Missing | 7 (5%) | NR | NR | NR | NR |
The baseline characteristics of the external validation cohort (QUALITAS study patients) is shown alongside the published characteristics of the development and previously published external validation cohorts. Age, performance status, number of metastatic sites, localization of metastases, number of prior treatment regimens, exposure to prior systemic anticancer agents, CEA, leukocytes and LDH were all determined at refractory disease, prior to starting FTD/TPI treatment. Abbreviations: CRC (colorectal cancer), CUP (Compassionate Use Program), FTD/TPI (trifluridine/tipiracil), IQR (interquartile range), mCRC (metastatic colorectal cancer), No. (number), NR (not reported), SD (standard deviation). a Synchronous disease was defined as stage IV CRC at diagnosis. b We assumed that RAS and BRAF mutations are mutually exclusive. c Prior exposure to fluoropyrimidine, oxaliplatin, and irinotecan. d Time to chemorefractoriness.