The total number of somatic mutations identified was normalized to the exonic coverage of the respective MSK-IMPACT panel in megabases. Mutations in driver oncogenes were not excluded from the analysis. Overall survival analysis on ICI patients was performed from the date of first infusion of any ICI. For patients who received multiple courses of ICI, the first treatment was used for analysis.Patients were censored at the date of last attended appointment at MSK if death was not recorded in the electronic medical record.
For analysis of patients who did not receive ICI, all patients for whom MSK-IMPACT data was available across all histologies were included. Overall survival analysis was performed from the date of first infusional chemotherapy.
Survival analysis was performed using Kaplan Meier with log-rank p values reported. Multivariable analysis was performed using Cox proportional hazard regression with inclusion of variables significant on univariate regression including normalized TMB, cancer type, age, ICI drug class , and year of ICI administration. Year of ICI administration was included in order to avoid any possible differences in patients treated in the early years of MSK-IMPACT testing being available.
For each histology, we subsequently identified cases in the top 20% percentile of TMB and determined the log-rank p-value for difference in OS and the direction of the effect with a HR determined from a coxph model. Additional analyses were performed with the TMB cutoff ranging from 10 to 50%, as well as with the TMB cutoff instead defined among all patients (both ICI-treated and non-ICI-treated).
Response data for individual histologies was obtained from published analyses of clinical outcome in the cohorts of patients with NSCLC or esophagogastric cancer patients.15 (link),16 (link). For patients with head and neck cancer, radiology records were reviewed manually to determine evidence of progression or tumor response. In these tumor types, clinical benefit was defined as any partial/complete response, or evidence of stable disease for ≥6 months. For renal cell carcinoma, time to next treatment was recorded manually for all patients.Statistical analysis was performed in R using the survival package. Graph-Pad Prism was used for basic analysis and generating graphs.Additional information can be found in the Life Sciences Reporting Summary.
For analysis of patients who did not receive ICI, all patients for whom MSK-IMPACT data was available across all histologies were included. Overall survival analysis was performed from the date of first infusional chemotherapy.
Survival analysis was performed using Kaplan Meier with log-rank p values reported. Multivariable analysis was performed using Cox proportional hazard regression with inclusion of variables significant on univariate regression including normalized TMB, cancer type, age, ICI drug class , and year of ICI administration. Year of ICI administration was included in order to avoid any possible differences in patients treated in the early years of MSK-IMPACT testing being available.
For each histology, we subsequently identified cases in the top 20% percentile of TMB and determined the log-rank p-value for difference in OS and the direction of the effect with a HR determined from a coxph model. Additional analyses were performed with the TMB cutoff ranging from 10 to 50%, as well as with the TMB cutoff instead defined among all patients (both ICI-treated and non-ICI-treated).
Response data for individual histologies was obtained from published analyses of clinical outcome in the cohorts of patients with NSCLC or esophagogastric cancer patients.15 (link),16 (link). For patients with head and neck cancer, radiology records were reviewed manually to determine evidence of progression or tumor response. In these tumor types, clinical benefit was defined as any partial/complete response, or evidence of stable disease for ≥6 months. For renal cell carcinoma, time to next treatment was recorded manually for all patients.Statistical analysis was performed in R using the survival package. Graph-Pad Prism was used for basic analysis and generating graphs.Additional information can be found in the Life Sciences Reporting Summary.
