Session VI: Colorectal Cancer I

SESSION VI WEBCAST (with Slides - needs a registration)

 

Late-Breaking Abstract-5: ANCHOR CRC: a single-arm, phase 2 study of encorafenib, binimetinib plus cetuximab In previously untreated BRAF V600E–mutant metastatic colorectal cancer

The authors conclude that ANCHOR is the first prospective study using a BRAF inhibitor-based therapy in1st-line BRAF^v600 mutant mCRC. The study population had a high median age (67yrs), a high proportion of elderly pts (61% ≥65 yrs), and an advanced stage at diagnosis (56% ECOG 1, 78% had metastases to at least 2 organs, 51% had peritoneal metastasis). This 1st-line BRAF^v600 metastatic CRC population is notably different from that observed in retrospective analyses of prior studies. A high confirmed objective response rate is observed (50%). Almost all pts had a decrease in tumor size. The median PFS of 5 months is similar to that observed with chemotherapy in 1line-BRAF^v600 mutant mCRC. The triplet combination was well-tolerated and manageable with no unexpected toxicities. Most frequent AEs are comparable to those observed with the same triplet combination in the BEACON study. Having reached the minimal number of confirmed responses in stage 1, the futility analysis allowed the authors to enroll additional pts in stage 2. The study is ongoing, results on all 95 pts will be communicated in 2021.

 

Late-Breaking Abstract-7: Encorafenib (ENCO) plus Cetuximab (CETUX) With or Without Binimetinib (BINI) for BRAFV600E Metastatic Colorectal Cancer (mCRC): Relationship Between Carcinoembryonic Antigen (CEA), and Clinical Outcomes from BEACON CRC

The authors conclude that in BEACON CRC, about 77% of pts with BRAF V600E-mutant metastatic CRC had elevated CEA levels at baseline. Across all treatment arms, low baseline CEA levels were associated with better OS. In pts with higher CEA levels at baseline, reduction in CEA was more commonly observed in the experimental arms (52-60%) vs control (1-6%)and was associated with improved OS. Of note in the experimental arms, early transient CEA decrease was commonly noted, even in pts with progression as best response, suggesting the rapid evolvement of resistance mechanisms in a subgroup of pts.

 

Merck Satellite Symposium:

Meet the Experts: Role of Anti-EGFRs beyond the First Line (1L) - Later Line Treatment Opportunities

Webcast from Wednesday, July 1 (Needs registration at WCGIC)

 

Short Oral-16: The tumour-stroma ratio as additional parameter to the TNM classification; the UNITED Study

The authors conclude that E-learning is an effective method to instruct pathologists for scoring TSR, confirming the reproducibility of the TSR scoring method. It is easily learned from auto instruction and short training. Semi-automated analysis can be helpful for pathologists when scoring TSR, for quantifying the exact stroma percentage. Especially around the cut-off area. Ther is a prospective study amongst 11 countries which is still including new centers.

 

Short Oral-17: Association between tumor budding grade to T stage as prognostic value for recurrence with high-risk stage II colon cancer; a retrospective study

The authors conclude that on multivariate analysis, T4 stage, BD3, and >12 lymph nodes were identified as the independent high-risk factors affecting RFS (p<0.05). The 5-year RFS rates i pts with both BD3 and T4 stage were significantly lower than those in pts without T4 stage (66.6% vs. 78.5%).

The pts with pStage II CRC and both T4 and BD3 factors have poor prognostic features and should be considered for adjuvant chemotherapy. 

 

Short Oral-18: Single-arm multicentre phase II study of bevacizumab (B) combined with 9-weekly alternating CAPOX and CAPIRI as first-line treatment of patients with metastatic colorectal cancer (mCRC): main results of the AXOAXI-trial

The authors conclude that with alternating B-CAPOX/B-CAPRI there is a high 12-month PFS rate: 62%. This is clearly better than in historical controls (44%). It was observed a high resectability and resection rate: 26%/25%. PFS was 16.6 months and OS 28.2 months. Mutational status was prognostic with promising survival also in BRAF^v600 mutant. Toxicity was acceptable with only 5% grade 3-4 neuropathy.

 

Short Oral-19: S-1 is a cost-effective alternative to capecitabine in metastatic colorectal cancer

The authors conclude that all three treatment strategies fall well within conservative willingness-to-pay thresholds in these mCRC pts who are not fit for combination treatment with platinum. S-1 plus bevacizumab is a cost-effective option for 1st-line treatment and even more as salvage after capecitabine-induced hand-foot syndrome. In pts with projected increase baseline risk for hand-foot syndrome - a risk that is currently based on clinical expertise, S-1 with bevacizumab as well as S1 salvage with bevacizumab are cost-saving compared to capecitabine with bevacizumab treatment. 

 

Short Oral-20: Consensus Molecular subtypes and CRCAssigner classifications in metastatic colorectal cancer (mCRC): prognostic and predictive impact in the TRIBE2 study

The authors conclude that CMS and CRCA classifiers identified subgroups with different characteristics (CMS prognostic, CRCA potentially predictive). Consensus Molecular Subtypes confirmed their prognostic role even in a population with a high rate of RAS/BRAF mutant pts, synchronous disease, and right-sided primary tumors. The nanoCMS assay employed to derive the CMS subtypes, which used a limited number of genes (38 genes) could explain the atypical distribution of CMS1 (1%) and CMS4 (52%). The benefit of FOLFOXIRI plus bev is independent across the CRCA subtypes, however stem-like and mixed subtypes seem to derive higher benefit from the upfront chemotherapy intensification when compared to doublets plus bev. The possible predictive ability of CRCA classifier (performed with the NanoCRCA assay) with regard to the intensification of 1st-line chemotherapy could be worthy of further investigations.

 

Short Oral-21: Management of adverse events associated with encorafenib plus cetuximab in patients with BRAF V600E-mutant metastatic colorectal cancer (The BEACON CRC Study)

The authors conclude that in the BEACON CRC study, encorafenib plus cetuximab significantly improved overall survival and objective response rates relative to standard of care in pts with BRAF^v600 mutant mCRC. Safety data were consistent with the known profiles of both encorafenib and cetuximab. Adverse events that occurred with encorafenib plus cetuximab were generally manageable, reversible, and infrequently associated with treatment discontinuation. Practical approaches to adverse event management can be employed by both pts and health care professionals to help mitigate the impact of these events. 

 

P-18 REMARRY and PURSUIT trials: Liquid biopsy-guided re-challenge of anti-EGFR monoclonal antibody for patients with RAS/BRAF V600E wild-type metastatic colorectal cancer (Abstract on page S95) ongoing study

 

Short Oral-22: Atypical non-V600E BRAF (aBRAF) mutations as a prognostic and predictive factor in real-life metastatic colorectal cancer patients from the Nordic countries

The authors conclude that aBRAFmt represents a distinct subgroup regarding gender, primary tumor location, metastatic sites, and MSI-H status. There is a slightly better OS than in BRAF^v600 mutant. aBRAFmt shows shorter OS and PFS compared with RAS/BRAFwt and RAmt, contrary to previous studies. Bevacizumab seems to prolong survival in aBRFmt. aBRAF may be a negative predictive marker for anti-EGFR efficacy. aBRAF derives benefit from metastasectomy. 

 

Short Oral-23: Prognostic impact of microsatellite instability/mismatch repair deficiency on patients with stage III colon cancer and stage IV colorectal cancers (CRC): analysis of 42,984 Patients in the National Cancer Database (NCDB)

The authors conclude that pts with MSI-H CRC are more likely to be white, and female with poorly differentiated and right-sided tumors, as well as less likely to present with metastatic disease., compared to pts with MSS tumors. After accounting for tumor location, gender, race, treatment, tumor differentiation, and insurance status, MSI-H/dMMR status had no prognostic impact on the OS in pts with either stage III colon cancer or stage IV CRC. Further prospective analyses of data incorporating BRAF mutation status and Lynch vs. sporadic CRC are warranted.  

 

Oral-16: Relative impact of T4 and N2 on the efficacy of 3 versus 6 months of adjuvant CAPOX for high-risk stage II and stage III colon cancer: ACHIEVE and ACHIEVE-2 trials

The authors conclude that T4 tumors had a negative impact on the efficacy of 3m CAPOX. Regardless of invasiveness (T4N0-T4N2), 3m CAPOX was worse than 6m. N2 tumors did not have a negative impact on the efficacy of 3m CAPOXwhen pts did not have T4. Further application of 3, CAPOX in addition to T1-3N1 may be possible. Interestingly, T4 tumors showed a different pattern of relapse (might have different tumor biology?). Further confirmation in large sample data would be warranted. 

 

Oral-17: A TNM-Immune (TNM-I) classification staging system for predicting survival in colon cancer in a multicenter international SITC study

 

Oral-18: Tumor mutational load, microsatellite instability, BRCAness, and actionable alterations in metastatic colorectal cancer: Results from the TRIBE2 study

The authors conclude that NGS profiling of mCRC provides novel insights with some potential clinical implications: to dissect the genomic landscape of mCRC, by identifying and characterizing new molecular subgroups. To refine the estimation of prognosis. To unveil the role of some genomic alterations in affecting tumor sensitivity to conventional 1st-line treatments.

TML-high tumors are not limited to MSI-High ones but may also present POLE or MSH6 somatic mutations and have favoraböe outcome. No differences are reported between TML-Low and -intermediate tumors. 

 

Oral-19: Feasibility of switching patients to S-1 upon other fluoropyrimidine-related cardiotoxicity during chemotherapy for gastrointestinal cancer

The authors conclude that Cardiotoxicity related to fluoropyrimidines is often severe or life-threatening. It starts rapidly after chemotherapy initiation, usually cycles 1 or 2, and on day 4 from the start line. It often leads to permanent fluoropyrimidine cessation, with a great lack of treatment alternatives in GI-cancer, especially in the curative setting (72% of patients had switched). 

Switching to S-1: Recurrent cardiotoxicity was seen only in 5 pts (3.7%; CI95% 1.5-8.6%; grade 1 in four and grade 2 in one; discontinuation in 1 of 137 pts (0.7%). S-1 can be combined with all other treatments. Cytotoxics combined were platinums, anthracyclines, taxanes, antimetabolites, topoisomerase 1 inhibitors, and alkylating agents. Biologics combined included bevacizumab and trastuzumab. Chemoradiation was also feasible. The study shows that switching to S-1 based therapy is feasible. It allows pts to continue a pivotal fluoropyrimidine-based regimen.