Session VIII: Colorectal Cancer: Metastatic Disease
The study authors conclude that for patients with previously treated mCRC, the addition of napabucasin - a first-in-class, investigational, orally-administered, reactive oxygen species generator bioactivated by the intracellular antioxidant NAD(P) H:quinone oxidoreductase - to FOLFIRI plus/minus bevacizumab did not improve overall and progression-free survival, disease control rate, or ORR in either the GSP or the BM+ population. TEAEs were consistent with previously published data.
The study authors conclude that for patients with MSI-H/dMMR mCRC, pembrolizumab 1st-line versus chemotherapy provides statistically superior progression-free survival with fewer treatment-related adverse effects. It is associated with a trend toward reduced mortality that did not meet statistical significance likely due to the high crossover rate from chemotherapy to anti-PD1/PD-L1 therapies. According to the authors, all these data confirm pembrolizumab as a new standard-of-care in the 1st-line for patients with MSI-H/dMMR mCRC.
The study authors conclude that nivolumab plus low-dose ipilimumab provided durable clinical benefits (ORR, PFS, and OS) over 13.4, 25.4, and 50.9 months of follow-up. Extended follow-up showed increasing ORR and deepening of response, with a manageable safety profile without new safety signals. According to the authors, these results demonstrate the long-term benefit of nivolumab plus low-dose ipilimumab for previously treated patients with MSI-H/ dMMR mCRC.
The study authors conclude that due to events unrelated to Cohort 1, the MODUL study was closed to enrolment prematurely; results from the Cohort 1 efficacy analysis are therefore descriptive only. Exploratory biomarker findings demonstrated that selective pressure of the treatment arm leads to acquired mutations that reactivate and converge in the MAPK pathway as drivers of resistance to cetuximab + vemurafenib.
Eric Van Cutsem
The study authors present the ANCHOR CRC study which is the first prospective study using a BRAF in- inhibitor-based therapy in first-line BRAFV600E-mutant mCRC. The study reveals that despite the high-risk features of the population enrolled in this study, almost half of the patients responded, and most had disease control, with a median progression-free survival of 5.8 months and a median overall survival of 17.2 months with an acceptable safety profile and manageable toxicities.
The study authors evaluated in this exploratory post hoc analysis the overall survival in patients from BEACON CRC treated with encorafenib plus cetuximab with or without binimetinib to investigate the potential effects of prior bevacizumab treatment on subsequent regimens for patients with BRAF V600E-mutant mCRC. (Tabernero J, et al. J Clin Oncol. 2021;39(4):273e284.)
The study authors demonstrate that preoperative ctDNA was detected in greater than 90% of the patients by personalized ctDNA assay based on unique somatic variants specific to each patient. Based on the associations of ctDNA-based MRD status and tissue biomarkers they observed, they are suggesting the ctDNA potential for reflecting biological aggressiveness related to biomarkers.
The study authors observed in patients with TRK fusion-positive GI cancer rapid responses with larotrectinib with high survival rates and a favorable safety profile. They conclude that these results support testing for NTRK gene fusions in patients with GI cancer, particularly in patients with MSI-H CRC.
A. Shamseddine Y. Zeidan Y. Bouferraa, et al.
The study authors conclude that based on their analysis, the primary endpoint was successfully met with significant improvement in pCR (37.5%, p=0.025) and mpRR rates in the setting of an acceptable safety profile. They will report the 3-year disease-free survival and overall survival later in the final study manuscript.
P-52: Overall survival with cetuximab every 2 weeks vs standard once-weekly administration schedule for first-line treatment of RAS wild-type metastatic colorectal cancer in patients with left- and right-sided primary tumor location
S. Kasper A. Cheng M. Rouyer, et al.
The study authors conclude that patients with right-sided primary tumors had a shorter median overall survival time versus patients with left-sided primary tumors. The authors' subgroup analyses support the conclusion of noninferiority in overall survival for cetuximab 500 mg/m2 every 2 weeks versus weekly 250 mg/m2 in the first-line treatment of RAS wild-type mCRC in combination with chemotherapy among patients with left- and right-sided primary tumors.
M. Kastrisiou G. Zarkavelis A. Kougioumtzi, et al.
The study authors conclude that their study is an example of the viability of liquid biopsy testing in a real-world setting. According to the authors, ctDNA testing by BEAMing seems to be an accurate alternative to tissue testing, especially in the presence of liver metastasis. They note, that repeat RAS testing can be informative at first progression, while the role of RAS MAF as a predictive biomarker needs further study.
D. Ciardiello V. Famiglietti S. Napolitano, et al.
The study authors conclude that in the CAVE mCRC study, baseline neutrophil to lymphocyte ratio < 3 was strongly correlated with improved survival and may represent a useful biomarker to predict response to retreatment with cetuximab plus avelumab.