Session VII: Presentation of Selected Colorectal Cancer Abstracts
The study authors show, that In this real-life/population-based cohort, there were no significant differences in patient characteristics, treatments provided, and outcomes between the 91 KRAS-G12Cmt cases compared to those with other KRAS or NRAS mutations. They conclude that this contrasts with the results of previous studies claiming differences in several aspects, however, not consistently. To show differences between rare tumor properties, the study authors propose large and non-selected patient series, especially, when specific drugs are developed, as for this mutation. Hopefully, differences in outcome will emerge.
The study authors demonstrated that KRAS G12C mutation was significantly correlated with shorter first-line progression-free - and overall survival compared to non-G12C mutations. These findings indicate the importance of a stratified treatment targeting KRAS G12C mutation in mCRC.
The study authors' data suggest that G12D and G12V are the most common KRAS variants across gastrointestinal malignancies; however, the distribution of KRAS variants significantly differed by cancer type. G12C was most frequently observed in patients with appendiceal, colorectal, small bowel, biliary, and pancreatic cancers. G12C was not detected in squamous cell carcinomas of the esophagus or anal canal.
The study authors showed with the NORDIC9-study that reduced-dose SOx was more effective in maintaining global QoL and physical function compared to full-dose S1, resulting in a clinically relevant difference according to the EORTC MID values at 9 weeks of treatment. They observed no clinically relevant difference in global QoL after 18 weeks, while the clinically relevant difference was maintained in physical functioning in favor of the SOx group. Considering their findings, and the significantly improved progression-free survival seen in the SOx group, they suggest that reduced-dose combination chemotherapy may be the treatment of choice in vulnerable older patients with mCRC, rather than full-dose monotherapy.
The study authors showed that the mean HRQoL with both EQ-5D and 15D is at a high level during active treatment for mCRC. The best HRQoL is seen for patients over 6 months after curative resection/LAT and is similar for upfront resectable, converted, or for single resections/LAT over multiple procedures. Lower values were seen in patients treated beyond the second line and particularly during a best supportive care phase.
The study authors conclude that the global POLAR program did not meet the primary objective. The etiology of increased CIPN symptoms is unclear.
The study authors conclude that the PRECONNECT study showed consistent results with the previously demonstrated safety and efficacy profile of trifluridine/tipiracil, with no new safety concerns identified. Progression-free survival and time to ECOG PS deterioration increased with duration of treatment, and quality of life was maintained during treatment. They finally conclude that these data provide additional support for the use of trifluridine/tipiracil in the treatment of mCRC in daily clinical practice.
SO-19: A multicenter phase Ⅱ trial of trifluridine/tipiracil in combination with cetuximab in RAS wild-type metastatic colorectal cancer patients refractory to prior anti-EGFR antibody therapy: the WJOG8916G trial
The study authors conclude that trifluridine/tipiracil in combination with cetuximab rechallenge proved to be safe. However, this trial did not show clinically meaningful DCR in RAS wild-type mCRC patients refractory to prior anti-EGFR antibody.
The study authors conclude that this experience met to prospectively validate Ang-2 baseline levels as prognostic marker and its early modulation as a predictor of benefit from regorafenib in mCRC patients.
The study authors conclude that patients with CRC with isolated liver metastases who were treated with neoadjuvant chemotherapy had statistically significant improvement in overall survival compared to patients who were treated with adjuvant chemotherapy. According to the authors these results are hypothesis-generating and indicate the need for confirmation of these results in the setting of prospective randomized studies.
The study authors conclude that the average cumulative relative dose (ACRD) is more important than the average relative dose intensity in determining survival. Elevated BMI is associated with a reduced cycle 1 dose and a modest ACRD reduction. The authors conclude that these in-direct effects through under-treatment might explain poorer survival in obese patients, rather than direct effects of obesity resulting from, for example, tumor biology.
According to the study authors MARS model, the three most important risk factors associated with mortality in patients with colon cancer stage II are
- Less than 14 lymph nodes examined,
- Elevated CEA level,
- T4 staging (vs T3), in that order.
They further conclude that CEA level could be considered to be incorporated in national guidelines as an important risk factor to guide the administration of adjuvant chemotherapy. Prospective validation of CEA level as a mortality marker in patients with stage II colon cancer is needed.
According to the study authors, minimal residual disease was identified in 18% of resected MMRd tumors using ctDNA analysis, suggesting this to be a feasible tumor agnostic approach to test the efficacy of CPB in patients at high risk for recurrence.
According to the study authors, this prospective, serial, and large-scale ctDNA profiling study reveals the temporal heterogeneity of mCRC-related somatic variants, which should be given special attention in clinical practice, as evidenced by the finding that the shift in RAS/ BRAF mutational status can yield a drastic change in survival outcomes.
According to the study authors, RAS, BRAF, and PIK3CA muts in ctDNA were associated with worse clinical efficacy outcomes in mCRC patients receiving anti-EGFR antibody rechallenge plus trifluridine/tipiracil. They propose that a comprehensive genomic test using ctDNA immediately before anti-EGFR antibodies rechallenge might help determine its indication.
The study authors suggest with their preliminary data that cfDNA BRAF MAF may constitute a significant tumor load surrogate with correlation with overall survival. They conclude that cfDNA BRAF MAF and WES could help to identify three subgroups of patients with different prognostic and predictive features that could potentially have therapeutic implications.
According to the study authors, their findings suggest antibiotics may have a role in colon tumor formation across all age groups, particularly in those aged less than 50 years. According to the study authors, it is possible that exposure to antibiotics could be contributing to the observed increases in EOCRC, particularly in the proximal colon. If confirmed, their study will provide further reasons to reduce, where possible, frequent and unnecessary antibiotic prescribing.
According to the study authors, their predicted neoepitope set has an optimal coverage among LS patients in terms of HLA alleles, associated cancers, and prevalence. They conclude that these results are key to first perform ex vivo functional analysis to determine neoepitopes immunogenicity to later design a preventive antitumoral vaccine for LS.