Impact of time to treatment initiation on real-world (RW) outcomes in metastatic colorectal cancer (mCRC) in the United States.
Authors: Gbolahan Olumide B. , Outlaw Darryl Alan , Hashemi Neda , Paluri Ravi Kumar , Williams Grant Richard 
Published: June 2021

3595

Background: The COVID-19 pandemic caused disruptions in cancer care delivery and forced oncologists to make recommendations about safely delaying initiation of therapy. Compared to the adjuvant setting, information about the impact of time to treatment initiation on outcomes in the palliative setting for CRCis scarce. We sought to determine the median time to initiation of systemic therapy (TIT) in mCRC in the US pre-pandemic, and to assess the impact of TIT on survival outcomes. Methods: We retrospectively analyzed de-identified data of patients (pnts) with mCRC in the Flatiron Health nationwide EHR-derived database (metastatic diagnosis dates 01/2013 - 04/202000. Demographics, treatments (tx), and outcomes were collected. TIT, the period between diagnosis and initiation of first-line systemic therapy was split into 3 categories (I: < 2 weeks, II: 2- < 4 weeks, and III: 4-8 weeks). Overall survival (OS) was defined from time of diagnosis to time of death. Post-chemotherapy survival (PCS) was time from initiation of first-line therapy to death. Adjusted and unadjusted multinomial logistic regression were used to evaluate the association of demographics and clinical factors with TIT. PCS and OS were estimated using Kaplan-Meier curves. Adjusted (demographics and clinical factors) Cox proportional hazard models were used to estimate the effect of TIT groups on PCS and OS. Category II was control group. Results: 7,108 pnts with mCRC who received at least one line of tx were identified. 16% (N = 1132), 34% (N = 2406), and 50% (N = 3570) were in TIT categories I-III. The mean age at diagnosis was 63.4 years, with no significant difference in age (P = 0.6) among categories. Median TIT was 28 days. Multinomial logistic regression showed that compared to TIT II, Hispanic pnts were more likely than Whites to receive chemotherapy in 4-8 weeks (OR 1.4, 95% CI 1.12- 1.7, P= 0.0022). Females were more likely to receive treatment in 4-8 weeks (OR 1.14, 95% CI 1.03- 1.27, P= 0.01). Pnts without documented KRAS testing were more likely to receive tx within 2 weeks (OR 1.3, 95% CI 1.05- 1.48, P= 0.01). Median RW OS favored group III (I: 18.1, II: 22.6, III: 26.9, P< 0.0001). Adjusted Cox regression analysis suggested that Blacks had a higher hazard of death compared to Whites, (HR, 1.14. 95% CI 1.03 -1.27, P = 0.01) Also, compared to TIT of 2-4 weeks, TIT < 2 weeks was associated with lower RW PCS (HR, 1.22, 95% CI 1.11- 1.33, P= 0.0001), and RW OS (HR, 1.25, 95% CI 1.14- 1.37, P= <0.0001). In contrast, TIT 4-8 weeks was associated with higher RW PCS (HR, 0.81, 95% CI 0.75- 0.87, P= 0.0001) and RW OS (HR, 0.78, 95% CI 0.72- 0.83 P= <0.0001. Conclusions: This RW analysis suggests that pre-pandemic, 50% of patients with mCRC who receive first-line therapy were treated within 4 weeks of diagnosis. We observed disparities in TIT. Paradoxically, RW survival increased with TIT, with the best outcomes reported in those treated in 4-8 weeks.