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. 2023 Feb 13;7(1):16.
doi: 10.1038/s41698-023-00353-4.

Survival improvement for patients with metastatic colorectal cancer over twenty years

Fadl A Zeineddine  1 , Mohammad A Zeineddine  1 , Abdelrahman Yousef  1 , Yue Gu  1 , Saikat Chowdhury  1 , Arvind Dasari  1 , Ryan W Huey  1 , Benny Johnson  1 , Bryan Kee  1 , Michael S Lee  1 , Maria Pia Morelli  1 , Van K Morris  1 , Michael J Overman  1 , Christine Parseghian  1 , Kanwal Raghav  1 , Jason Willis  1 , Robert A Wolff  1 , Yoshikuni Kawaguchi  2 , Jean-Nicolas Vauthey  2 , Ryan Sun  3 , Scott Kopetz  1 , John Paul Shen  4
Affiliations

Survival improvement for patients with metastatic colorectal cancer over twenty years

Fadl A Zeineddine et al. NPJ Precis Oncol. .

Abstract

Over the past two decades of successive clinical trials in metastatic colorectal cancer (CRC), the median overall survival of both control and experimental arms has steadily improved. However, the incremental change in survival for metastatic CRC patients not treated on trial has not yet been quantified. We performed a retrospective review of 1420 patients with de novo metastatic CRC who received their primary treatment at the University of Texas M.D. Anderson Cancer Center (UTMDACC) from 2004 through 2019. Median OS was roughly stable for patients diagnosed between 2004 and 2012 (22.6 months) but since has steadily improved for those diagnosed in 2013 to 2015 (28.8 months), and 2016 to 2019 (32.4 months). Likewise, 5-year survival rate has increased from 15.7% for patients diagnosed from 2004 to 2006 to 26% for those diagnosed from 2013 to 2015. Notably, survival improved for patients with BRAFV600E mutant as well as microsatellite unstable (MSI-H) tumors. Multivariate regression analysis identified surgical resection of liver metastasis (HR = 0.26, 95% CI, 0.19-0.37), use of immunotherapy (HR = 0.44, 95% CI, 0.29-0.67) and use of third line chemotherapy (regorafenib or trifluridine/tipiracil, HR = 0.74, 95% CI, 0.58-0.95), but not year of diagnosis (HR = 0.99, 95% CI, 0.98-1), as associated with better survival, suggesting that increased use of these therapies are the drivers of the observed improvement in survival.

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Conflict of interest statement

AD is an advisor for HutchMed; Personalis Inc; AAA / Novartis; Ipsen and receives research funding from Eisai, HutchMed; Guardant Health; Xencor. BJ is an advisor for Gritstone bio; Incyte; Taiho Oncology; Insmed Oncology and research funding from Bristol-Myers Squibb; Syntrix; Gateway for Cancer Research. CP receives honoraria from Merck and Pfizer and research support from Amgen, Inc and Lilly. KR is an advisor for Bayer; Daiichi; AstraZeneca; Seattle Genetics and receives research funding from Guardant, Bayer; Daiichi; AstraZeneca; Amgen, Medimmune. MSL is an advisor for Pfizer; Delcath and receives research funding from EMD Serono, Inc; Amgen, Inc, Bristol-Myers Squibb Co; Pfizer, Inc; Genentech/Roche; Exelixis, Inc, and Rafael Pharmaceuticals; MO is an advisor for Takeda Pharmaceuticals; Pfizer; Merck; Glaxosmithkline and receives research funding from Roche; Takeda; Merck; BMS. VM is an advisor for Incyte; SERVIER; Boehringer Ingelheim; Axiom Healthcare Strategies; BioMedical Insights; Bicara Therapeutics and receives research funding from Immatics; Bristol-Myers Squibb; EMD Serono; Pfizer; BioNTech AG; Bicara Therapeutics. SK has ownership interest in Lutris, Iylon, Frontier Medicines, Xilis, Navire and is a consultant for Genentech, EMD Serono, Merck, Holy Stone Healthcare, Novartis, Lilly, Boehringer Ingelheim, AstraZeneca/MedImmune, Bayer Health, Redx Pharma, Ipsen, HalioDx, Lutris, Jacobio, Pfizer, Repare Therapeutics, Inivata, GlaxoSmithKline, Jazz Pharmaceuticals, Iylon, Xilis, Abbvie, Amal Therapeutics, Gilead Sciences, Mirati Therapeutics, Flame Biosciences, Servier, Carina Biotech, Bicara Therapeutics, Endeavor BioMedicines, Numab, Johnson & Johnson/Janssen, Genomic Health, Frontier Medicines, Replimune, Taiho Pharmaceutical, Cardiff Oncology, Ono Pharmaceutical, Bristol-Myers Squibb-Medarex, Amgen, Tempus, Foundation Medicine, Harbinger Oncology, Inc, Takeda, CureTeq, Zentalis, Black Stone Therapeutics, NeoGenomics Laboratories, Accademia Nazionale Di Medicina, and receive research funding from Sanofi, Biocartis, Guardant Health, Array BioPharma, Genentech/Roche, EMD Serono, MedImmune, Novartis, Amgen, Lilly, Daiichi Sankyo; JPS is an advisor for Engine Biosciences and receives research funding from Celsius Therapeutics. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Overall survival for patients with metastatic colorectal cancer treated at M.D. Anderson Cancer Center by year of diagnosis.
a Kaplan–Meier overall survival curves for metastatic CRC patients group by year of diagnosis, log-rank p-value comparing all curves <0.0001. b Five-year survival rate according to year of diagnosis. For 2016 to 2019, this has not yet reached.
Fig. 2
Fig. 2. Hepatic Resection of Liver Metastasis.
a Percentage of patients undergoing liver resection by date of diagnosis, note increase after 2014. b Overall survival by landmark analysis of patients with metastatic colorectal cancer diagnosed between 2004 and 2019, error bars represent 95% CI, Log-rank p < 0.0001.
Fig. 3
Fig. 3. Chemotherapy utilization changes over time.
a The percentage of each chemotherapy administered to patients between 2004 and 2019, binned by year, note use of novel chemotherapeutics increased after 2012. b Percentage of patients treated with novel drugs, IO Immunotherapy, Tri/TI Trifluridine/Tipiracil.
Fig. 4
Fig. 4. Overall survival for patients with metastatic colorectal cancer with either BRAF mutation or microsatellite instability.
a Kaplan–Meier overall survival curves for patients with BRAF mutation before and after 2014, error bars represent 95% CI, log-rank p = 0.04. Median overall survival (b) and three-year survival rate (c) for patients with BRAF mutation, note improvement after 2015. Kaplan–Meier overall survival curve (d), median overall survival, error bars represent 95% CI, log-rank p = 0.008 (e) and three-year survival rate (f) for MSI-H patients, note improvement after 2015 where median overall survival is not-yet-reached. Number of patients indicated above bar plot.
Fig. 5
Fig. 5. Overall survival for patients with metastatic colorectal according to primary tumor location.
a Kaplan–Meier overall survival curves comparing patients based on primary site location, log-rank p < 0.0001. Kaplan–Meier overall survival curves showing the change in overall survival of patients with left (b) and right (c) sided tumors. d Median overall survival of patients according to tumor location binned by time of diagnosis. e Five-year survival rate according to tumor location binned by time of diagnosis. For 2016 to 2019, this has not yet reached.
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