Supplementary Figures from Association of TP53 Mutational Status and Gender with Survival after Adjuvant Treatment for Stage III Colon Cancer: Results of CALGB 89803

Warren, Robert S.; Atreya, Chloe E.; Niedzwiecki, Donna; Weinberg, Vivian K.; Donner, David B.; Mayer, Robert J.; Goldberg, Richard M.; Compton, Carolyn C.; Zuraek, Marlene B.; Ye, Cynthia; Saltz, Leonard B.; Bertagnolli, Monica M.

doi:10.1158/1078-0432.22449344.v1

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Supplementary Figures from Association of TP53 Mutational Status and Gender with Survival after Adjuvant Treatment for Stage III Colon Cancer: Results of CALGB 89803

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posted on 2023-03-31, 17:30 authored by Robert S. Warren, Chloe E. Atreya, Donna Niedzwiecki, Vivian K. Weinberg, David B. Donner, Robert J. Mayer, Richard M. Goldberg, Carolyn C. Compton, Marlene B. Zuraek, Cynthia Ye, Leonard B. Saltz, Monica M. Bertagnolli

Supplementary Figures - PDF file 341K, Figure S1. CALGB 89803 Consolidated Standards of Reporting Trials (CONSORT) diagram. Cancer and Leukemia Group B (CALGB) 89803 conducted a randomized trial of adjuvant therapy in patients with stage III colorectal cancers. The trial included prospective determination of the relationship between tumor TP53 mutational status, gender, and treatment outcome as a secondary study end point. CPT-11, irinotecan; FU, fluorouracil; LV, leucovorin. Figure S2. Kaplan-Meier estimates of disease-free survival related to TP53 status for men and women in CALGB 89803. A. DFS in the presence or absence of any TP53 mutation showed no differences among women (P = 0.16). B. Similarly, DFS in the presence or absence of any TP53 mutation showed no differences among men (P = 0.16). WT = wild type TP53; Mutant = any TP53 mutation in exons 5-8). Corresponding 5 year survival estimates are in Table 2, Rows 5 and 6. Figure S3. Kaplan-Meier estimates of disease-free survival related to TP53 status among men in CALGB 89803. Men whose tumors harbored wild-type (WT) TP53, or tumors with mutations in the zinc-binding (ZB) or non-zinc binding (NZB) domains of TP53 were treated with 5FU/LV (Figure S3A) or IFL (Figure S3B). No differences in survival according to TP53 genotype were observed among men treated with 5FU/LV (P = 0.65) or IFL, P = 0.14. Corresponding 5 year survival estimates are in Table 2, Rows 16-17. Figure S4. Kaplan-Meier estimates of disease-free survival related to TP53 status among women in CALGB 89803. Women whose tumors harbored wild-type TP53, or tumors with mutations in the zinc-binding (ZB) or non-zinc binding (NZB) domains of TP53 were treated with 5FU/LV or IFL. (A) Women with TP53 WT tumors experienced a statistically similar outcome on either treatment arm (P = 0.35. (B) Women whose tumors harbored ZB mutations may have benefited marginally from IFL as compared to 5FU/LV (P = 0.10). (C) Women whose tumors harbored NZB mutations experienced a trend toward better survival with 5FU/LV compared to IFL (P = 0.08)

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ARTICLE ABSTRACT

Purpose: The TP53 tumor suppressor is frequently mutated in colon cancer, but the influence of such mutations on survival remains controversial. We investigated whether mutations in the DNA-binding domain of TP53 are associated with survival in stage III colon cancer.Experimental Design: The impact of TP53 genotype was prospectively evaluated in Cancer and Leukemia Group B 89803, a trial that randomized stage III colon cancer patients to receive adjuvant 5-fluorouracil/leucovorin (5FU/LV) or 5FU/LV with irinotecan (IFL).Results:TP53 mutations were identified in 274 of 607 cases. The presence of any TP53 mutation did not predict disease-free survival (DFS) or overall survival with either adjuvant regimen when men and women were considered together or as separate groups. However, outcome differences among women became apparent when tumor TP53 genotype was stratified as wild-type versus zinc- or non-zinc-binding mutations in the TP53 DNA-binding domain. DFS at 5 years was 0.59, 0.52, and 0.78 for women with TP53 wild-type tumors, and tumors with zinc- or non-zinc-binding mutations, respectively. Survival at 5 years for these same women was 0.72, 0.59, and 0.90, respectively. No differences in survival by TP53 genotype were observed in men.Conclusions: The presence of any TP53 mutation within the DNA-binding domain did not predict survival in stage III colon cancer. However, TP53 genotype was predictive of survival in women following adjuvant therapy. Future colon cancer therapeutic trials, with inclusion of correlative molecular markers, should be designed to permit evaluation of survival and/or response to treatment in women separately from men. Clin Cancer Res; 19(20); 5777–87. ©2013 AACR.