Pts received 1500 mg/m 2 NUC-3373 +/-400 mg/m 2 LV on Days 1 and 15 of a 28-day cycle. Plasma and PBMC samples were collected during first 2 cycles. Safety was assessed throughout.Results: PK profiles from 17 matched pairs from Q2W dosed pts were available (n ¼ 21 pts). PK parameters for NUC-3373 were similar +/-LV and interpatient variability was low. Increasing intracellular FUDR-MP concentrations were associated with an increase in intracellular dUMP concentrations. NUC-3373 was well tolerated +/-LV. Highest grade treatment-related adverse events (TRAEs) were grade 3 hyponatremia (1 pt) and grade 4 bilirubin increased (1 pt). No pts discontinued NUC-3373 due to TRAEs.Conclusions: NUC-3373 demonstrated a favourable PK profile with a long plasma halflife and high volume of distribution. The association between increasing FUDR-MP with increasing dUMP concentrations indicates NUC-3373's ability to inhibit TS, preventing conversion of dUMP to dTMP. PK parameters for NUC-3373 +/-LV were similar indicating LV has no PK interaction with NUC-3373. NUC-3373 was well tolerated +/-LV. These findings suggest that LV is an appropriate combination partner for NUC-3373. Clinical trial identification: NCT03428958.Legal entity responsible for the study: NuCana plc.

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registered 3686 CRC patients and 1840 CRC patients died. Despite the fact that significant progress has been made in the treatment of CRC in recent years, this disease is still one of the leading causes of mortality from cancer pathology. Methods: Retrospective study of 287 patients with advance colorectal cancer who tested the mutational status of the KRAS gene. 60.2% of patients have negative and 39.8% of patients have positive mutational status of the KRAS gene. The most common forms of mutation are G12D (12.5%), G13D (10.1%) G12V (8.4%). Right side of intestinum lesion was in 42 (14.6%) patients, left side intestinum in 128 (44.6%) patients, rectum in 117 (40.8%) patients. Median of follow-up was 25.1 month. Overall survival (OS) was calculated from the start of treatment to death from any cause or until the date of the last appearance of the patient. Survival was estimated by Kaplan-Meier survival curves, comparison of curves by Log rank test. Results: OS 24%, median was 24 months, SE 0.9, CI 95% (22.3 -25.7). Risk factor differences not significant for: gender (v2 ¼ 0.01 h ¼ 0.9), ethnic group (v2 ¼ 0.19 h ¼ 0.7), age < 50 survival median was 27-months, age > 50 survival median was 24 months (v2 ¼ 2.46 h ¼ 0.12). Standard chemotherapy survival median was 24-months, target chemotherapy survival median was 26 months (v2 ¼ 0.25 h ¼ 0.62). Adenocarcinoma histology type survival median was 25 months, for mucosa histology type survival median was 17 months (v2 ¼ 1.1 h ¼ 0.29). Positive mutational status of the KRAS gene survival median was 24 months. Positive mutational status of the KRAS gene survival median was 24 months. For T3 category survival median was 26 months for T4 spread was 24 months (v2 ¼ 2.1 h ¼ 0.15). For new metastasis during treatment survival median was 24 months, for no metastases during treatment survival median was 27 months (v2 ¼ 1.03 h ¼ 0.31). Differences in OS was significant for: metastasis in regional lymph nodes, survival median was 23 months, N0 survival median was 27,4 months (v2 ¼ 12.1 h ¼ 0,01). G3 tumor differentiation survival median was 20 months, for G2 survival median was 26 months, G1 survival median was 28 months (v2 ¼ 7.78 h ¼ 0,02). Intestinum right side OS was 26.2%, survival median 24 months, left side OS was 27.3% survival median 26 months, rectum OS was 19.7% survival median 21 months (v2 ¼ 4.8 h ¼ 0,04). Conclusion: Metastasis in regional lymph nodes and G3 tumor differentiation are significant risk factors for advance colorectal cancer.

registered 3686 CRC patients and 1840 CRC patients died. Despite the fact that significant progress has been made in the treatment of CRC in recent years, this disease is still one of the leading causes of mortality from cancer pathology. Methods: Retrospective study of 287 patients with advance colorectal cancer who tested the mutational status of the KRAS gene. 60.2% of patients have negative and 39.8% of patients have positive mutational status of the KRAS gene. The most common forms of mutation are G12D (12.5%), G13D (10.1%) G12V (8.4%). Right side of intestinum lesion was in 42 (14.6%) patients, left side intestinum in 128 (44.6%) patients, rectum in 117 (40.8%) patients. Median of follow-up was 25.1 month. Overall survival (OS) was calculated from the start of treatment to death from any cause or until the date of the last appearance of the patient. Survival was estimated by Kaplan-Meier survival curves, comparison of curves by Log rank test. Results: OS 24%, median was 24 months, SE 0.9, CI 95% (22.3 -25.7). Risk factor differences not significant for: gender (v2 ¼ 0.01 h ¼ 0.9), ethnic group (v2 ¼ 0.19 h ¼ 0.7), age < 50 survival median was 27-months, age > 50 survival median was 24 months (v2 ¼ 2.46 h ¼ 0.12). Standard chemotherapy survival median was 24-months, target chemotherapy survival median was 26 months (v2 ¼ 0.25 h ¼ 0.62). Adenocarcinoma histology type survival median was 25 months, for mucosa histology type survival median was 17 months (v2 ¼ 1.1 h ¼ 0.29). Positive mutational status of the KRAS gene survival median was 24 months. Positive mutational status of the KRAS gene survival median was 24 months. For T3 category survival median was 26 months for T4 spread was 24 months (v2 ¼ 2.1 h ¼ 0.15). For new metastasis during treatment survival median was 24 months, for no metastases during treatment survival median was 27 months (v2 ¼ 1.03 h ¼ 0.31). Differences in OS was significant for: metastasis in regional lymph nodes, survival median was 23 months, N0 survival median was 27,4 months (v2 ¼ 12.1 h ¼ 0,01). G3 tumor differentiation survival median was 20 months, for G2 survival median was 26 months, G1 survival median was 28 months (v2 ¼ 7.78 h ¼ 0,02). Intestinum right side OS was 26.2%, survival median 24 months, left side OS was 27.3% survival median 26 months, rectum OS was 19.7% survival median 21 months (v2 ¼ 4.8 h ¼ 0,04). Conclusion: Metastasis in regional lymph nodes and G3 tumor differentiation are significant risk factors for advance colorectal cancer.

Introduction: local treatment of metastases is an integral part of colon cancer treatment. However, there is not enough data on the efficacy of surgical resection of metastases in patients with a BRAF gene mutation to recom‑mend this approach in routine practice. We initiated a retrospective multicenter study to assess the incidence of BRAF gene mutations in patients with metastatic colon cancer and to study the efficacy of metastasectomy in this group of patients.Materials and methods: we selected all patients who underwent surgical resection of metastases in various sites from the database of patients with BRAF gene mutations created as a result of a multicenter retrospective study with participation of 7 clinics in the Russian Federation. All 57 patients with RAS gene mutations and 43 patients with wild‑type RAS and BRAF genes who also underwent surgical resection of metastases at any stage of treatment were selected from the register of the Chemotherapy Department No. 2 of the NMRC of Oncology named after N. N. Blokhin for comparative analysis. Disease‑free survival and overall survival were used as primary efficacy criteria.Results: we found 26 patients with BRAF gene mutations who underwent surgical resection of metastases. When comparing disease‑free survival, the worst median was achieved in the group of patients with BRAF gene mutations: 7 months versus 14 months in patients with RAS gene mutations (HR 0.4, 94 % CI 0.23–0.7, P = 0.006); median disease‑free survival was not achieved in the wild‑type RAS and BRAF group (HR 0.2, 95 % CI 0.11–0.45, P <0.001).The median overall survival in the BRAF gene mutation group was 26 months versus 38 months in the RAS gene mutations group (HR 0.8, 95 % CI 0.33–1.98, P = 0.6) and 49 months in the wtRAS/wtBRAF group (RR 0.46, 95 % CI 0.17–1.24, P = 0.1). Resection of recurrent tumors in patients with metastases in retroperitoneal lymph nodes was associated with extremely low disease‑free survival (2 months); at the same time, disease‑free survival was 7 months after resection of isolated metastases in the liver and 8 months for metastases in the peritoneum.Conclusion: prognosis of patients with a BRAF gene mutation after surgical resection of metastases is worse than in patients with a different mutation phenotype. Nevertheless, literature data, as well as the results of our study, confirm the possibility of performing metastasectomy with careful selection of patients.