Skin Toxicity as Predictor of Survival in Refractory Patients with RAS Wild-Type Metastatic Colorectal Cancer Treated with Cetuximab and Avelumab (CAVE) as Rechallenge Strategy
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design and Patient Population
2.2. Patient Monitoring and Response Assessment
2.3. qPCR Analysis of Plasma Samples
2.4. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Univariate Analysis | Multivariate Analysis | ||||
---|---|---|---|---|---|
Variable | Number of Patients | Hazard Ratio (CI 95%) | p-Value | Hazard Ratio (CI 95%) | p-Value |
Skin Rash | |||||
Grade 0–1 | 44 (57.1%) | 1.00 (ref) | 1.00 (ref) | ||
Grade 2–3 | 33 (42.9%) | 0.495 (0.30–0.80) | 0.004 | 0.71 (0.39–1.27) | 0.25 |
Sex | |||||
Female | 35 (45.5%) | 0.89 (0.56–1.42) | 0.64 | ||
Male | 42 (54.5%) | 1.00 (ref) | |||
ECOG | |||||
0 | 52 (67.5%) | 0.78 (0.48–1.31) | 0.37 | ||
1 | 25 (32.5%) | 1.00 (ref) | |||
Lines of treatment | |||||
III | 56 (72.7%) | 1.00 (ref) | |||
>III | 21 (27.3%) | 0.87 (0.51–1.47) | 0.61 | ||
Number of metastatic sites | |||||
≤II | 45 (58.4%) | 0.54 (0.33–0.87) | 0.013 | 0.72 (0.41–1.25) | 0.24 |
>II | 32 (41.6%) | 1.00 (ref) | 1.00 (ref) | ||
Surgery of the primary tumor | |||||
Yes | 48 (62.3%) | 0.58 (0.36–0.94) | 0.028 | 0.70 (0.41–1.20) | 0.20 |
No | 29 (37.7%) | 1.00 (ref) | 1.00 (ref) | ||
Microsatellites Instability | |||||
MSI | 3 (5.41%) | 0.59 (0.18–1.91) | 0.59 | ||
MSS | 71 (95.9%) | 1.00 (ref) | |||
Sidedness | |||||
Left and rectum | 72 (93.5%) | 0.45 (0.17–1.15) | 0.096 | ||
Right | 5 (6.5%) | 1.00 (ref) | |||
Synchronous metastases | |||||
Yes | 56 (72.7%) | 1.00 (ref) | |||
No | 21 (27.3%) | 0.64 (0.37–1.10) | 0.11 | ||
RAS/BRAF/EGFR mutational status | |||||
WT | 48 (71.6%) | 0.41 (0.23–0.75) | 0.004 | 0.58 (0.3–1.08) | 0.10 |
MT | 19 (28.4%) | 1.00 (ref) | 1.00 (ref) |
Univariate Analysis | Multivariate Analysis | ||||
---|---|---|---|---|---|
Variable | Number of Patients | Hazard Ratio (CI 95%) | p-Value | Hazard Ratio (CI 95%) | p-Value |
Skin Rash | |||||
Grade 0–1 | 44 (57.1%) | 1.00 (ref) | 1.00 (ref) | ||
Grade 2–3 | 33 (42.9%) | 0.51 (0.29–0.89) | 0.019 | 0.54 (0.29–0.1.01) | 0.054 |
Sex | |||||
Female | 35 (45.5%) | 1.03 (0.60–1.76) | 0.90 | ||
Male | 42 (54.5%) | 1.00 (ref) | |||
ECOG | |||||
0 | 52 (67.5%) | 0.64 (0.36–1.11) | 0.11 | ||
1 | 25 (32.5%) | 1.00 (ref) | |||
Lines of treatment | |||||
III | 56 (72.7%) | 1.00 (ref) | |||
>III | 21 (27.3%) | 1.12 (0.63–1.99) | 0.69 | ||
Number of metastatic sites | |||||
≤II | 45 (58.4%) | 0.74 (0.43–1.27) | 0.28 | ||
>II | 32 (41.6%) | 1.00 (ref) | |||
Surgery of the primary tumor | |||||
Yes | 48 (62.3%) | 0.65 (0.38–1.11) | 0.12 | ||
No | 29 (37.7%) | 1.00 (ref) | |||
Microsatellites Instability | |||||
MSI | 3 (5.41%) | 1.25 (0.30–5.1) | 0.75 | ||
MSS | 71 (95.9%) | 1.00 (ref) | |||
Sidedness | |||||
Left and rectum | 72 (93.5%) | 1.25 (0.44–3.47) | 0.67 | ||
Right | 5 (6.5%) | 1.00 (ref) | |||
Synchronous metastases | |||||
Yes | 56 (72.7%) | 1.00 (ref) | |||
No | 21 (27.3%) | 0.73 (0.39–1.37) | 0.34 | ||
RAS/BRAF/EGFR mutational status | |||||
WT | 48 (71.6%) | 0.50 (0.27–0.90) | 0.022 | 0.49 (0.27–0.90) | 0.023 |
MT | 19 (28.4%) | 1.00 (ref) | 1.00 (ref) |
Variable | Number of Patients | CR | PR | SD | PD |
---|---|---|---|---|---|
Skin toxicity | |||||
Grade 0–1 | 44 (57.1%) | 0 (0%) | 3 (6.8%) | 20 (45.5%) | 21 (47.7%) |
Grade 2–3 | 33 (42.9%) | 1 (3%) | 2 (6.1%) | 24 (72.7%) | 6 (18.2%) |
Sex | |||||
Female | 35 (45.5%) | 1 (2.9%) | 3 (8.6%) | 21 (60%) | 10 (28.6%) |
Male | 42 (54.5%) | 0 (0%) | 2 (4.8%) | 23 (54.8%) | 17 (40.5%) |
ECOG | |||||
0 | 52 (67.5%) | 1 (1.9%) | 4 (7.7%) | 29 (55.8%) | 18 (34.6%) |
1 | 25 (32.5%) | 0 (0%) | 1 (4.0%) | 15 (60%) | 9 (36.0%) |
Lines of treatment | |||||
III | 56 (72.7%) | 1 (1.8%) | 3 (5.4%) | 31 (55.4%) | 21 (37.5%) |
>III | 21 (27.3%) | 0 (0%) | 2 (9.5%) | 13 (61.9%) | 6 (28.6%) |
Number of metastatic sites | |||||
≤II | 45 (58.4%) | 1 (2.2%) | 2 (4.4%) | 29 (64.4%) | 13 (28.9%) |
>II | 32 (41.6%) | 0 (0%) | 3 (9.4%) | 15 (46.9%) | 14 (43.8) |
Surgery of the primary tumor | |||||
Yes | 48 (62.3%) | 1 (2.1%) | 4 (8.3%) | 31 (64.6%) | 12 (25%) |
No | 29 (37.7%) | 0 (0%) | 1 (3.4%) | 13 (44.8%) | 15 (51.7%) |
Microsatellites Instability | |||||
MSI | 3 (5.41%) | 0 (0%) | 0 (0%) | 3 (100%) | 0 (0%) |
MSS | 71 (95.9%) | 1 (1.4%) | 5 (7%) | 40 (56.3%) | 25 (35.2%) |
Sidedness | |||||
Left and rectum | 72 (93.5%) | 1 (1.4%) | 4 (5.6%) | 43 (59.7%) | 24 (33.3%) |
Right | 5 (6.5%) | 0 (0%) | 1 (20%) | 1 (20%) | 3 (60%) |
Synchronous metastases | |||||
Yes | 56 (72.7%) | 1 (1.8%) | 3 (5.4%) | 30 (53.6%) | 22 (39.3%) |
No | 21 (27.3%) | 0 (0%) | 2 (9.5%) | 14 (66.7%) | 5 (23.8%) |
RAS/BRAF/EGFR mutational status | |||||
WT | 48 (71.6%) | 1 (2.1%) | 3 (6.3%) | 31 (64.6%) | 13 (27.1%) |
MT | 19 (28.4%) | 0 (0%) | 1 (5.3%) | 8 (42.1%) | 10 (52.6%) |
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Ciardiello, D.; Famiglietti, V.; Napolitano, S.; Esposito, L.; Normanno, N.; Avallone, A.; Latiano, T.; Maiello, E.; Pietrantonio, F.; Cremolini, C.; et al. Skin Toxicity as Predictor of Survival in Refractory Patients with RAS Wild-Type Metastatic Colorectal Cancer Treated with Cetuximab and Avelumab (CAVE) as Rechallenge Strategy. Cancers 2021, 13, 5715. https://doi.org/10.3390/cancers13225715
Ciardiello D, Famiglietti V, Napolitano S, Esposito L, Normanno N, Avallone A, Latiano T, Maiello E, Pietrantonio F, Cremolini C, et al. Skin Toxicity as Predictor of Survival in Refractory Patients with RAS Wild-Type Metastatic Colorectal Cancer Treated with Cetuximab and Avelumab (CAVE) as Rechallenge Strategy. Cancers. 2021; 13(22):5715. https://doi.org/10.3390/cancers13225715
Chicago/Turabian StyleCiardiello, Davide, Vincenzo Famiglietti, Stefania Napolitano, Lucia Esposito, Nicola Normanno, Antonio Avallone, Tiziana Latiano, Evaristo Maiello, Filippo Pietrantonio, Chiara Cremolini, and et al. 2021. "Skin Toxicity as Predictor of Survival in Refractory Patients with RAS Wild-Type Metastatic Colorectal Cancer Treated with Cetuximab and Avelumab (CAVE) as Rechallenge Strategy" Cancers 13, no. 22: 5715. https://doi.org/10.3390/cancers13225715