primelines June GI updates ASCO 2017

Emerging Data in Gastrointestinal Cancers from the American Society of Clinical Oncology (ASCO) Annual Meeting

Using risk-based approach to personalize adjuvant chemotherapy duration for stage III colon cancer. According to a prospective pooled analysis of six phase III adjuvant colon cancer clinical trials with 12,800 patients, a 3-month course of adjuvant combination chemotherapy of oxaliplatin and intravenous 5-fluorouracil (FOLFOX) or oxaliplatin and oral capecitabine (CAPOX) has similar efficacy and substantially lower rates of adverse events when compared to a 6-month course of chemotherapy. Results of this important analysis conducted by the IDEA (International Duration Evaluation of Adjuvant Chemotherapy) collaboration were presented by Qian Shi, PhD (Mayo Clinic Cancer Center, Rochester, Minnesota, United States), at the Plenary Session (Abstract LBA1). Three months of adjuvant chemotherapy was associated with a 3-year disease-free survival (DFS) of 74.6%, compared to 75.5% with 6 months of chemotherapy (HR 1.07). DFS varied by regimen, with FOLFOX favoring a 6-month course (HR 1.16) and CAPOX demonstrating true noninferiority of the 3-month treatment (HR 0.95). A subgroup analysis demonstrated that the 3-month chemotherapy was the most appropriate for low-risk patients (defined as T1-3N1), which includes approximately 60% of stage III patients, while patients with high-risk disease (T4 and/or N2) benefit from 6 months of chemotherapy. Importantly, patients receiving 3 months of treatment had significantly lower rates of grade 2 and higher neurotoxicity (3 m vs 6 m: 17% vs 48% [FOLFOX] and 15% vs 45% [CAPOX]; P = .0001) and higher rates of treatment compliance. Based on these results, the investigators recommend a risk-based approach to selecting adjuvant chemotherapy duration, with patients with low-risk disease receiving 3 months of treatment and those with high-risk disease receiving 6 months, based on tolerability and patient preference. The discussant, Cathy Eng, MD (University of Texas MD Anderson Cancer Center, Houston, Texas, United States), commented that while these results are important, the analysis did not meet its primary endpoint of noninferiority for DFS, and thus the standard of care for stage III colon cancer should remain 6 months oxaliplatin-based chemotherapy until further data are available. However, she recognized that only a minority of patients are able to tolerate 6 months oxaliplatin-based therapy.

Adjuvant capecitabine, a new standard-of-care for biliary tract cancers. Results from the BILCAP randomized study (Abstract 4006) of 447 patients with resected biliary tract cancers, presented by John Primrose, MD (University of Southampton, Southampton, United Kingdom), found that 8 cycles of adjuvant capecitabine improved overall survival (OS) by 15 months compared to observation. Capecitabine was associated with a median 51.1 months OS, compared to 36.4 months with observation (HR 0.81, P = .097). Similar improvements were also seen in relapse-free survival (RFS: 24.6 months vs 17.6 months; HR 0.76, P = .039). Adverse events (AEs) associated with capecitabine were manageable, with hand-foot skin reaction as the most common grade 3/4 AE (21%). Quality of life was not impaired for patients receiving capecitabine. Dr Primrose concluded that based on these results, adjuvant capecitabine should become the standard of care in this setting and serve as the control arm for future adjuvant trials in patients with biliary tract cancer.

Perioperative FLOT regimen improves survival in gastric cancer. According to results from a multicenter, randomized phase III trial, perioperative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) significantly improves OS and PFS compared to current standard epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) in patients (N = 716) with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (Abstract 4004). FLOT was associated with a median 50 months OS, compared to 35 months with ECF/ECX (HR 0.77, P = .012). Additionally, PFS improved by 12 months in patients receiving FLOT (30 months vs 18 months; HR 0.75, P = .004). Rates of serious AEs were similar between the two treatment groups, and treatment with FLOT did not increase surgical morbidity or mortality, resurgeries, or hospitalization times compared to ECF/ECX. Presenter Salah-Eddin Al-Batran, MD (Krankenhaus Nordwest-University Cancer Center, Frankfurt, Germany), concluded that these results support FLOT as the new standard of care in perioperative treatment of gastric or GEJ adenocarcinoma. The discussant, Yoon-Koo Kang, MD, PhD (Asan, Medical Center, Seoul, Korea), agreed that a 9% improvement in 5- year OS is clinically meaningful and that FLOT regimen can be considered a new standard in perioperative chemotherapy for localized advanced gastric cancer.

Immune checkpoint inhibitors continue to demonstrate activity in gastroesophageal cancers. Updated results from the large phase II KEYNOTE-059 trial (Abstract 4003), demonstrated that treatment with pembrolizumab (200 mg every 3 weeks) resulted in an ORR of 11.6% and reduction in tumor in 42.4% of patients. Patients with PD-L1–positive tumors had an ORR of 15.5%, with 2% having complete response; however, responses were seen also in PD-L1 negative patients. Best responses were seen in patients with MSI-H tumors, where ORR was 57.1%, consistent with other studies examining the efficacy of pembrolizumab in MSI-H tumors. Updates from the phase I/II CheckMate 032 study of combination nivolumab and ipilimumab in Western patients with advanced/metastatic esophagogastric cancer were also presented (Abstract 4014). Patients receiving nivolumab 1 mg/kg and ipilumumab 3 mg/kg had an objective response rate (ORR) of 24%, compared with 12% in patients receiving only nivolumab 3 mg/kg. Responses on the combination were dependent on dosing, as only 8% patients who received an alternate dose strategy (nivolumab 3 mg/kg and ipilumumab 1 mg/kg) responded. Median OS was 6.9 months, 6.2 months, and 4.8 months, respectively. Responses were observed regardless of PD-L1 status. Compared to nivolumab alone, combinations, in particular nivolumab 1 and ipilimumab 3, were associated with higher serious toxicity (10% vs 43%).

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