Sachin G Pai1, Benedito A Carneiro2,3, Young Kwang Chae2,3, Ricardo L Costa2,3, Aparna Kalyan2,3, Hiral A Shah2,3, Irene Helenowski4, Alfred W Rademaker4, Devalingam Mahalingam5, Francis J Giles2,3. 1. Department of Interdisciplinary Clinical Oncology, Mitchell Cancer Institute, University of South Alabama, Mobile, AL, USA. 2. Developmental Therapeutics Program, Division of Hematology/Oncology, Feinberg School of Medicine, Chicago, IL, USA. 3. Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA. 4. Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 5. Cancer Therapy and Research Center, University of Texas Health Science Center San Antonio, San Antonio, TX, USA.
Abstract
BACKGROUND: The Cancer Genome Atlas (TCGA) showed that 16% of colorectal cancers (CRCs) display DNA repair mechanisms and high tumor mutational burden (TMB). Although, there is accumulating evidence of greater benefit of immunotherapy in tumors with high-TMB, its impact on response to chemotherapy is unknown. METHODS: In this retrospective cohort study, we investigated the impact of TMB on progression-free survival (PFS) of CRC patients treated at tertiary care oncology clinics who had their tumors profiled by next-generation sequencing (NGS). Low TMB (TMB-L) and intermediate/high TMB (TMB-I/H) were defined as ≤5 mutations per base (MB) or ≥6 MB, respectively. RESULTS: Seventy-four CRC patients (61 colon and 13 rectal cancers) were identified from the database. In the TMB-L cohort, irinotecan-based chemotherapy treated patients had improved PFS compared to oxaliplatin-based chemotherapy treated patients (11.9 vs. 6.5 months, P<0.001). No difference in PFS was observed between the two treatment cohorts in TMB-I/H group. There was also no difference in time to recurrence in the TMB-L and TMB-I/H arms in patients treated with oxaliplatin-based therapy in perioperative setting. CONCLUSIONS: TMB-L may be a predictive biomarker in a subset of CRC patients treated with chemotherapy but these results need to confirmed in larger studies.
BACKGROUND: The Cancer Genome Atlas (TCGA) showed that 16% of colorectal cancers (CRCs) display DNA repair mechanisms and high tumor mutational burden (TMB). Although, there is accumulating evidence of greater benefit of immunotherapy in tumors with high-TMB, its impact on response to chemotherapy is unknown. METHODS: In this retrospective cohort study, we investigated the impact of TMB on progression-free survival (PFS) of CRC patients treated at tertiary care oncology clinics who had their tumors profiled by next-generation sequencing (NGS). Low TMB (TMB-L) and intermediate/high TMB (TMB-I/H) were defined as ≤5 mutations per base (MB) or ≥6 MB, respectively. RESULTS: Seventy-four CRC patients (61 colon and 13 rectal cancers) were identified from the database. In the TMB-L cohort, irinotecan-based chemotherapy treated patients had improved PFS compared to oxaliplatin-based chemotherapy treated patients (11.9 vs. 6.5 months, P<0.001). No difference in PFS was observed between the two treatment cohorts in TMB-I/H group. There was also no difference in time to recurrence in the TMB-L and TMB-I/H arms in patients treated with oxaliplatin-based therapy in perioperative setting. CONCLUSIONS: TMB-L may be a predictive biomarker in a subset of CRC patients treated with chemotherapy but these results need to confirmed in larger studies.
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