Session VI: Colorectal Cancer I
SESSION VI WEBCAST (with Slides - needs a registration)
The authors conclude that ANCHOR is the first prospective study using a BRAF inhibitor-based therapy in1st-line BRAFv600 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 BRAFv600 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-BRAFv600 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)
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.
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 BRAFv600 mutant. Toxicity was acceptable with only 5% grade 3-4 neuropathy.
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.
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.
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 BRAFv600 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
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 BRAFv600 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.
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.
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.
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.
Posters with trifluridine/tipiracil
PD-7 Updated survival analysis of the Danish randomized study comparing trifluridine/tipiracil with or without bevacizumab in patients with chemo-refractory metastatic colorectal cancer (abstract on page S214)
The authors conclude that updated survival analyses confirm that FTD/TPI in combination with bevacizumab prolongs PFS and OS and is a new valuable option in patients with chemo-refractory mCRC. Results on markers for no benefit and time to deterioration of performance status will be presented.
The authors conclude that their real-life single-center results show that regorafenib and trifluridine/tipiracil have similar efficacy and safety among the Bulgarian population compared with previously acquired global data.
The authors conclude that their data show that treatment with trifluridine/tipiracil in daily clinical practice is feasible and safe. Forty-eight patients (39%) achieved clinical benefit with trifluridine/tipiracil. Patient characteristics such as left side primary tumor location, WT KRAS status, WT BRAF status, more than 3 lines of previous treatment, ECOG PS 0, and Platelet-to-Lymphocyte Ratio.
The authors conclude that comparing their data with those of the RECOURSE study, they can say that the SG and PFS of their patients were significantly lower. This may be due to the fact that they included patients with ECOG 2, rapid progressors, as well as a higher percentage of patients who required hospital admission due to toxicity. The adverse events of their patients were similar to those described in the RECOURSE study, except for asthenia and febrile neutropenia, which were significantly higher in their study.
P-190 A retrospective study of regorafenib versus trifluridine/tipiracil efficacy in chemorefractory metastatic colorectal cancer patients: Multi-institution real-life clinical data (Abstract on page 152)
The authors conclude that no significant difference between regorafenib and TAS-102 sequence treatments was observed in patients with mCRC. Further analyses are ongoing to potentially identify a biomarker or a clinical sub-group to distinguish the two drugs.
The authors aimed to investigate the outcomes and safety of TAS-102 treatment in a real-world setting. Their results, being comparable with previously reported studies, further demonstrate the clinical benefit of TAS-102 for refractory mCRC patients with manageable toxicities. Furthermore, the benefit was derived regardless of tumor characteristics or previous treatment received.
The authors conclude that their RWD on TFT was associated with a better OS than expected. This RWD study was able to validate GPC, GPC with no liver metastases and grade