Treatment and Survival Outcomes by Age Following Second-Line Therapy for Metastatic CRC (mCRC): Analysis of 13,149 Patients from the ARCAD Clinical Trials Program

Background: We evaluated the time to progression and survival outcomes of second-line therapy for metastatic colorectal cancer among adults aged 70 years and older compared to adults aged less than 70 years following progression on first-line clinical trials. Methods: Associations between clinical and disease characteristics, time to initial progression and rate of receipt of second-line therapy were evaluated. Time to progression and overall survival were compared between older and younger adults enrolled on second-line trials by Cox regression, adjusting for age, sex, ECOG PS, number of metastatic sites and presence of metastasis in the lung, liver or peritoneum. Findings: Older adults comprised 16·4% of enrolled patients on first-line trials. Older adults and those with ECOG PS >0 were less likely to receive second-line therapy than younger adults. Odds of receiving second-line therapy decreased by 11% for each additional decade of life in multivariate analysis (p-value = 0·0117). Older and younger adults enrolled in second-line trials experience similar median time to progression and median overall survival (5·1 vs. 5·2 months; 11·6 vs. 12·4 months, respectively). Interpretation: Older adults are less likely to receive second-line therapy for metastatic colorectal cancer, though we did not observe a statistical difference in survival outcomes for older vs younger adults following second-line therapy. Further study is needed to examine factors, including patient preference, along with the effects of comorbidities and functional status impacting decisions to treat older adults with second-line therapy. Inclusion of geriatric assessment may provide more objective criteria regarding the risks and benefits of second-line therapy to aid decision making for older adults considering second-line therapy for metastatic colorectal cancer. Funding: The NCI GCC Spore Career Development Award (5P50CA127003-08) funded Dr. McCleary’s effort. The ARCAD Foundation funded data collection and analysis. Declaration of Interest: Alberto F Sobrero served on advisory boards and as a speaker at satellite symposia for Merck, Roche, Servier, Incyten, Sanofi, Bayer, Bristol Myers Squibb, Amgen, Eli Lilly, and Pierre Fabre. James M Cleary received research funding to his institution from Abbvie, Merus, Roche, and Bristol Myers Squib. He received research funding from Merck, Astrazeneca, Esperas Pharma, and Tesaro, received consulting fees from Bristol Myers Squibb, and received travel funding from Bristol Myers Squib. Volker Heinemann served as honoraria for Merck, Amgen, Roche, Sanofi, Sirtex, Servier, Pfizer. He served as a consultant or Merck, Amgen, Roche, Sanofi, Sirtex, and Bristol Myers Squibb. He served on an advisory board for Merck, Novartis, Boehringer Ingelheim, Servier, Pierre-Fabre, Celgene, and Terumo. He received research funding to his institution from Merck, Amgen, Roche, Sanofi, Pfizer, Boehringer-Ingelheim, Sirtex, Bayer, and Servier. He received travel funding from Merck, Roche, Amgen, Sirtex, Bayer, and Servier. Stuart M Lichtman is supported by the NCI Cancer Center Support Grant (P30CA008748). All other author have nothing to declare. Ethical Approval: All analyses were performed with approval from the local Institutional Review Board in accordance with the precepts of the Helsinki Declaration.