Claymore J. Cuny, PharmD BCPS
PGY-2 Oncology Resident
University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences
University of Colorado Hospital
University of Colorado Cancer Center
Aurora, CO

The 2018 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium welcomed more than 3,500 presenters and attendees from across the world to San Francisco, CA, January 18–20, making it the largest GI symposium to date. The following summary contains highlights from the meeting.

Perhaps the most controversial topic was presented in one of the afternoon breakout sessions on the opening day of the symposium. “FLOT or NOT: Preoperative Management for Gastric Cancer” stimulated a lively discussion on the utility of 5-FU, leucovorin, oxaliplatin, and docetaxel (FLOT) in patients with gastroesophageal cancer. Salah-Eddin Al-Batran, MD, took the pro-FLOT stance, and Jaffer Ajani, MD, took the NOT stance. The results of the FLOT4 trial, which compared FLOT to epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) was presented at ASCO”s 2017 Annual Meeting in Chicago, IL. FLOT was shown to improve median overall survival (mOS: 50 months vs. 35 months) and progression-free survival (mPFS; 30 months vs. 18 months).¹ However, there is concern over the tolerability of FLOT and the 30-day mortality (2%) seen in the study. Both presenters agreed that ECF/ECX should no longer be used in clinical practice, but they disagreed on whether FLOT should be the new standard of care or whether it should be reserved for patients who can tolerate high-intensity chemotherapy.

The results of the RAINFALL trial were also presented during the oral abstract session on day 1. RAINFALL assessed the clinical benefit of the addition of ramucirumab to first-line cisplatin with capecitabine or 5-fluorouracil in patients with metastatic gastric or gastroesophageal junction adenocarcinoma. The addition of ramucirumab was shown to have a hazard ratio (HR) of 0.75 (95% confidence interval [CI], 0.61–0.94) for disease progression or death but had only a slight increase in mPFS (5.7 months vs. 5.4 months) and was not associated with an improved OS.²

On day 2, Robin Kate Kelley, MD, presented on advances in molecular targeted therapies in cholangiocarcinoma. Multiple agents are in study, targeting FGFR2 fusions, with promising early improvements in objective response rate (ORR) and PFS. The ClarIDHy trial is ongoing in patients with previously treated advanced cholangiocarcinoma with mutant IDH1 to determine the PFS rate of ivosidenib, an oral IDH1 inhibitor. Other areas of discussion were DNA mismatch repair deficiency or microsatellite instability-high (dMMR/MSI-H), targeting BRAF and HER2, as well as unselected trials for ramucirumab, merestinib, and varlitinib in combination with chemotherapy. 

On the final day the first report was given of the full cohort of the CheckMate-142 trial. This trial evaluated nivolumab and ipilimumab in combination in patients with dMMR/MSI-H metastatic colorectal cancer (mCRC). Patients received nivolumab 3 mg/kg and ipilimumab 1 mg/kg every 3 weeks for 4 doses followed by nivolumab 3 mg/kg.³ The ORR was found to be 55%, and the disease control rate (DCR) was 80%, which may represent a new standard of care for patients with dMMR/MSI-H mCRC.³ In a separate abstract, the long-term survival of patients with dMMR/MSI-H mCRC receiving nivolumab according to prior treatment was also reported from the CheckMate-142 trial. Patients who received standard chemotherapy with fluorouracil, oxaliplatin, and irinotecan (group A) had an ORR of 26%, and those who received 2 or more prior lines of therapy (group B) had an ORR of 52%.⁴ The increased response rate in group B supports further investigation of nivolumab combinations in the first-line setting of mCRC.

The keynote lecture, “Mapping the Immune Landscape in Pancreatic Cancer,” delivered by Steven D. Leach, MD, discussed the immunologic characteristics of long-term pancreatic cancer survivors. In a group of long-term pancreatic cancer survivors there was evidence of enhanced tumor-specific T-cell response as well as an association with unique neoepitope quality and tumor neoepitopes associated with microbial pathogens.^5-7 These long-term survivors are thought to have T-cell clones that cross-react with tumor neoepitopes and microbial antigens.⁷

The 2019 ASCO GI Cancers Symposium will be held January 17–19 in San Francisco, CA. For more information on the symposium visit www.asco.org.

References

1. Al-Batran SE, Homann N, Schmalemberg H, et al. Perioperative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) versus epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (FLOT4-AIO): a multi center, randomized phase 3 trial. J Clin Oncol. 2017;35(suppl;abstr 4004). 
2. Fuchs CS, Shitara K, Bartolomeo MD, et al. RAINFALL: a randomized, double-blind, placebo controlled phase III study of cisplatin (Cis) plus capecitabine (Cape) or 5FU with or without ramucirumab (RAM) as first-line therapy in patients with metastatic gastric or gastroesophageal junction (G-GEJ) adenocarcinoma. (abstract). Gastrointestinal Cancer Symposium; 2018 Jan 18-20; San Francisco, CA. ASCO; 2018. Abstract 5.
3. Andre T, Lonardi S, Wong M, et al. Nivolumab + ipilimumab combination in patients with DNA mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC): First report of the full cohort from CheckMate-142 (abstract). Gastrointestinal Cancer Symposium; 2018 Jan 18-20; San Francisco, CA. ASCO; 2018. Abstract 553.
4. Overman MJ, Bergamo F, McDermott RS, et al. Nivolumab in patients with DNA mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC): long-term survival according to prior line of treatment from CheckMate-142 (abstract). Gastrointestinal Cancer Symposium; 2018 Jan 18-20; San Francisco, CA. ASCO; 2018. Abstract 554.
5. Balachandran VP, Luksza M, Zhao JN, et al. Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer. Nature. 2017 Nov 23;551(7681):512-516.
6. Luksza M, Riaz N, Makarov V, et al. A neoantigen fitness model predicts tumour response to checkpoint blockade immunotherapy. Nature. 2017 Nov 23;551(7681):517-520.
7. Leach SD. Mapping the immune landscape in pancreatic cancer [keynote address]. Gastrointestinal Cancer Symposium, 2018 Jan 18; San Francisco, CA.