Gastrointestinal Cancer—Colorectal and Anal

Hagen Fritz Kennecke, Carl J Brown, Jonathan M. Loree, et al.
The study authors conclude that In select patients with early stage rectal cancer, three months of induction CAPOX/FOLFOX followed by transanal Endoscopic Surgery resulted in a high Organ Preservation Rate without the use of pelvic irradiation. Clinical trial information: NCT03259035
Hannah Thompson, Jin Ki Kim, Jonathan B. Yuval, et al.
The study authors conclude that the 3-tier clinical response assessment has prognostic implications for organ preservation rates and disease-free survival in patients with locally advanced rectal cancer who underwent neoadjuvant therapy. In patients with a near-complete response, more than half achieved organ preservation at 3 years. The authors recommend, that this information should be utilized to counsel patients regarding their expected outcomes. Clinical trial information: NCT02008656
Jing Jin, Yuan Tang, Chen Hu, et al.
The study authors conclude that for locally advanced rectal cancer with high-risk factors, short-term radiotherapy combined with sequential chemotherapy was non-inferior to chemoradiotherapy and could be used as an alternative to long-term radiotherapy. Meanwhile, short-term radiotherapy combined with chemotherapy presented a higher clinically and radiologically complete response + pathological complete response and 3-year overall survival rates as compared with chemoradiotherapy. However, the long-term results need to be further followed up. (ClinicalTrails No.: NCT02533271). Clinical trial information: NCT00833131
Lisa Salvatore, Maria Bensi, Salvatore Corallo, et al.
The study authors conclude that the combination of preop chemoradiotherapy plus avelumab showed a promising activity and a feasible safety profile. The experimental regimen will be considered for further studies. Updated results are presented during the Congress. Clinical trial information: NCT03854799
Carlos Fernandez-Martos, Carles Pericay, Joan Maurel, et al.
The study authors conclude that the study met the threshold for efficacy. Neoadjuvant mFOLFOX6 plus panitumumab can be effective and safe. There were no unexpected toxicities in mrT3, clear MRF and 4WT rectal cancer. There was a higher rate of pathological complete response observed compared with the previous series in a similar molecular-unselected population. Clinical trial information: NCT03000374
Scott Kopetz, Danielle A. Murphy, Jie Pu, et al.
The study authors conclude that a subset of patients with specific molecular features may derive greater clinical benefit from triplet than doublet therapy. This is supported by observed molecular characteristics and biological properties in BRAF V600E-mutant mCRC.  According to the authors, these findings support the utility of gaining further understanding of the biological landscape in BRAF-mutant mCRC to enable potential hypotheses for patient selection to improve clinical outcomes in future studies. Clinical trial information: NCT02928224
Christine Megerdichian Parseghian, Ryan Sun, Stefania Napolitano, et al.
The study authors conclude that acquired KRAS, NRAS, BRAF, EGFR, or MAP2K1 MTs rarely develop after 1st-line therapy. This stands contrary to the expectations. According to the study, selective pressure appears to increase the frequency of acquired MTs in the 3L setting, however, preexisting subclonal MTs do not appear to be the dominant source of acquired MTs at progression. This implies a possible transient mutational process driving resistance rather than expansion of preexisting clones. These are significant implications for ongoing and planned EGFRi rechallenge studies.
Federico Innocenti, Akram Yazdani, Xueping Qu, et al.
The study authors conclude that tumor immune signatures in mCRC patients are determinants of survival. In patients treated with standard of care bevacizumab- and cetuximab-combinations, immune signatures affect response to therapy.  New markers for treatment selection and for the development of novel active combinations including immune checkpoint inhibitors are shown with the results in this study.
Katherine L. Pogue-Geile, Marion Joy, Ying Wang, et al.
The study authors conclude that CD8 cells were associated with better overall survival but were not associated with bevacizumab benefits. All T cells and PD-1, PD-L1, and LAG3 cells were associated with better prognosis in the entire cohort. However, when patients were stratified for MMR status differences in their association with prognosis and bevacizumab benefit emerged: PD-1, CD8, and CD8/PD-1 cells were associated with bevacizumab harm in proficient mismatch repair but bevacizumab benefit in deficient mismatch repair.
The authors state, that a significant interaction for the association of high % PD-1 and PD-L1 with bevacizumab benefit regardless of mismatch repair status may be a chance finding. However, VEGF has immunosuppressive effects and bevacizumab may block these effects in tumors with high PD-L1 and PD-1, regardless of mismatch repair status. Clinical trial information: NCT00096278.
Elisa Fontana, Jeffrey P. Meyers, Alberto F. Sobrero, et al.
The study authors conclude that early-onset colorectal cancer (eoCRC, age < 50) has better therapeutic adherence than late-onset CRC (loCRC, age ≥ 50), as expected. In high-risk stage II and low-risk stage III, cancer-specific outcomes are not different, however, in high-risk stage III young age is negatively prognostic and associated with significantly higher relapse rate and risk of colorectal cancer death; this is despite a higher adjuvant treatment intensity, suggesting more aggressive disease biology. 
Julia Stal, Serena Yi, Sally Cohen-Cutler, et al.
The study authors show in this study that most colorectal cancer survivors reported never having a fertility discussion with their provider. This suggests that survivors are not receiving, or cannot recall, comprehensive and guideline-concordant cancer care. One-fifth were not aware of preservation options, suggesting potential healthcare and/or provider-level barriers to appropriate fertility counseling. Fertility preservation cost is another barrier to the appropriate delivery of care. The study authors stress, that providers must ensure that patients receive timely fertility discussions covering options to preserve fertility to mitigate this late effect of cancer treatment to ensure optimal quality of life for CRC patients with reproductive potential.
Ning Jin, Xiaokui Mo, Rebecca Hoyd, Ayse Selen Yilmaz, et al.
The study authors conclude that their data suggest a mechanism by which the colorectal cancer-associated microbiota may be associated with epigenetic regulation and host immune response.

Final results from the CAVE (cetuximab rechallenge plus avelumab) mCRC phase II trial: Skin toxicity as a predictor of clinical activity.

Giulia Martini, Stefania Napolitano, Vincenzo Famiglietti, et al.

Rechallenge treatment with anti-epidermal growth factor receptor (EGFR) drugs in patients with RAS wild type (RAS WT) metastatic colorectal cancer (mCRC)  with promising antitumor activity has been recently reported. The study authors conclude that Cetuximab plus avelumab is effective and well-tolerated as a rechallenge treatment in mCRC. Skin toxicity is a clinical biomarker for the identification of RAS/BRAF mCRC patients that could benefit from anti-EGFR rechallenge. Clinical trial information: NCT04561336


Overall survival (OS) with encorafenib (enco) + cetuximab (cetux) in BEACON CRC: Effect of prior therapy for BRAF V600E-mutant metastatic colorectal cancer (mCRC).

Scott Kopetz, Dan Aderka, Axel Grothey,  et al.

The study authors conclude from this exploratory post-hoc analysis that In the BEACON CRC study, patients with the doublet encorafenib + cetuximab for BRAF V600E-mutant mCRC demonstrated similar overall survival regardless of prior therapies or duration of prior therapy use. This analysis provides data that reflect the prior treatment landscape clinicians may face when deciding subsequent treatment regimens for patients with BRAF V600E-mutant mCRC. Clinical trial information: NCT02928224