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Top Highlights From the 2015 ASCO Gastrointestinal Cancers Symposium

Top Highlights From the 2015 ASCO Gastrointestinal Cancers Symposium

  • MM-398 Combo Shows Benefit in Metastatic Pancreatic Cancer: Li-Tzong Chen, MD, PhD, presenting results from the phase III NAPOLI-1 trial, which found that combining MM-398 with 5-FU/leucovorin chemotherapy in metastatic pancreatic cancer patients previously treated with gemcitabine-based therapy resulted in improved survival compared with 5-FU/leucovorin alone. The overall survival analysis showed an advantage for patients taking the combination MM-398 plus 5-FU/leucovorin (6.1 months vs 4.2 months; stratified hazard ratio [HR] = 0.57; P = .0009). There was no significant survival advantage for patients assigned MM-398 alone compared with 5-FU/leucovorin alone. Photo by © ASCO/Todd Buchanan 2015.[1]
  • Low-Risk Group Can Avoid Surgery for Locally Advanced Rectal Cancer: A retrospective analysis of 145 stage I–III rectal cancer patients shows that those patients who have a complete response after chemoradiotherapy and chemotherapy had a similar 4-year survival rate regardless of whether they had surgery or opted for surveillance. In general, about 40% of patients with stage I–III disease have disappearance of their tumors after systemic therapy. The 4-year overall survival rate was 91% and 95% in the no surgery and standard surgery groups, respectively. There was no difference in the rate of distant recurrences between the two groups. “These data continue to suggest that non-operative management does not compromise oncologic outcome, and that preservation of the rectum is achieved in a majority of patients,” concluded the authors. Image source: Philip Paty, MD, Joshua Smith, MD, PhD, Memorial Sloan Kettering Cancer Center, New York City.[2]
  • Baseline AFP Levels Affect Ramucirumab Benefit in HCC: Andrew X. Zhu, MD, PhD, of Massachusetts General Hospital Cancer Center, presenting results from the phase III REACH study, which found that alpha-fetoprotein (AFP) levels could serve as a prognostic indicator in advanced hepatocellular carcinoma (HCC) patients treated with second-line ramucirumab. Treatment with ramucirumab resulted in a significant survival advantage for patients with a baseline AFP level of 400 ng/mL or greater (7.8 months vs 4.2 months; HR = 0.674; P = .0059). The drug did not confer a survival advantage among patients with lower baseline AFP levels (10.1 months vs 11.8 months). Photo by © ASCO/Todd Buchanan 2015.[3]
  • Small Molecule MET Inhibitor Active in Gastroesophageal Cancer: Of the 13 patients with MET-amplified tumors treated once daily with AMG-337, a small molecule MET inhibitor, 8 had a partial or near complete response. AMG-337 is a potent and selective inhibitor that targets both wild-type and some mutant forms of MET. The subset of patients with MET-amplified gastroesophageal junction, gastric, and esophageal cancers responded to treatment. One responder had tumor shrinkage of more than 90%. Based on these phase I results, a phase II trial in MET-amplified gastroesophageal junction, gastric, and esophageal cancers is currently ongoing. Image source: Eunice Kwak, MD, PhD, Massachusetts General Hospital, Boston.[4]
  • Minimally Invasive vs Open Esophagectomy in Esophageal Cancer: Christophe Mariette, MD, PhD, of the department of digestive and oncologic surgery, Claude Huriez University Hospital, presenting data from the phase III MIRO study that compared hybrid minimally invasive esophagectomy with open esophagectomy in 207 patients with esophageal cancer. There was a lower rate of postoperative morbidity in the minimally invasive arm compared with the open esophagectomy arm (35.9% vs 64.4%; P = .0001) and fewer pulmonary complications (17.7% vs 30.1%; P = .037). There was no difference in 30-day mortality (4.9% in each arm of the trial). The findings provide evidence for the short-term benefits of minimally invasive surgery for patients with resectable esophageal cancer. Photo by © ASCO/Todd Buchanan 2015.[5]
  • Adding Bevacizumab to Aggressive Chemo Regimen Doubles 5-Year Colorectal Cancer Survival: Frontline treatment with FOLFOXIRI chemotherapy plus bevacizumab in patients with metastatic colorectal cancer improved survival over FOLFIRI chemotherapy with bevacizumab by 4 months. The median overall survival was 29.8 months in the FOLFOXIRI group compared with 25.8 months in the standard FOLFIRI treatment group (P = .030). Patients in the FOLFOXIRI treatment arm were 20% less likely to die of their disease compared with those in the control arm. The more intensive chemotherapy regimen also doubled the 5-year overall survival rate from 12.4% in the FOLFIRI treatment arm to 24.9% in the FOLFOXIRI treatment arm. Image source: Chiara Cremolini, MD, Tuscan Tumor Institute, Pisa, Italy.[6]
  • Immunotherapy Produces Response in Gastric Cancer: Of the 39 advanced gastric cancer patients treated with the anti-PD-1 monoclonal antibody pembrolizumab, 22.2% had an objective response. The median time to response was 8 weeks. Five patients (13.9%) had stable disease. The median duration of response was 24 weeks and ranged from 8 to more than 33 weeks. The 6-month progression-free survival rate was 24% and the 6-month overall survival rate was 69%. The median follow-up was 8.8 months. Image source: Kei Muro, MD, Aichi Cancer Center Hospital, Nagoya, Japan.[7]
  • Radiation Therapy as Effective as Chemoradiotherapy at Reducing Dysphagia in Esophageal Cancer: Michael Gordon Penniment, MBBS, FRANZCR, MBA, of the Royal Adelaide Hospital, presenting results of a multinational phase III study that compared radiotherapy with chemoradiotherapy for the palliation of dysphagia in patients with advanced esophageal cancer. In patients treated with radiation therapy alone, 41% achieved a maintained improvement in swallowing; in patients treated with chemoradiotherapy, 47% achieved an improvement (P = .4163). Bowel toxicity was worse in patients who received chemoradiotherapy. Photo by © ASCO/Todd Buchanan 2015.[8]
  • Higher Vitamin D Levels, Better Colorectal Cancer Outcomes: Newly diagnosed metastatic colorectal cancer patients with higher vitamin D levels had better outcomes after treatment with a combination of chemotherapy and targeted therapy. The difference in median overall survival between the patients in the highest and lowest quintile of vitamin D levels was 8.1 months. The median overall survival was 32.6 months among patients with the highest vitamin D levels compared with 24.5 months for patients with the lowest vitamin D levels (P = .002). Patients with higher concentrations of circulating vitamin D were 20% less likely to have disease progression compared with those with low circulating vitamin D levels (P = .02). Image source: Kimmie Ng, MD, MPH, Dana-Farber Cancer Institute, Harvard Medical School, Boston.[9]
  • Lanreotide Delays Disease Progression in PNETs: Alexandria T. Phan, MD, presenting results of the CLARINET study, which found that lanreotide autogel/depot delayed disease progression in patients with metastatic pancreatic neuroendocrine tumors (PNETs). The trial randomized 91 patients to receive either lanreotide (n = 42) or placebo (n = 49). Median progression-free survival was not reached at study end in patients who received lanreotide vs 12.1 months in those who received placebo. The evidence of lanreotide’s antitumor effects along with favorable long-term safety data support the drug’s use as a first-line treatment for PNETs. Photo by © ASCO/Todd Buchanan 2015.[10]
  • Another Angiogenesis-Targeting Antibody Active in Advanced Colorectal Cancer: The combination of ramucirumab, an antiangiogenesis antibody, and second-line FOLFIRI chemotherapy delayed disease progression and increased survival slightly in patients with metastatic colorectal cancer who had previously progressed on first-line therapy. Patients treated with ramucirumab plus FOLFIRI were 16% less likely to die of their disease compared with those treated with FOLFIRI alone (P = .0219). Image source: Josep Tabernero, MD, Vall d’Hebron University Hospital, Barcelona.[11]
  • MET Inhibitor Fails to Delay Disease Progression in Gastroesophageal Cancer: Manish A. Shah, MD, of New York-Presbyterian Hospital, presenting results of a phase II trial that compared FOLFOX plus the MET inhibitor onartuzumab vs FOLFOX plus placebo in patients with advanced gastroesophageal adenocarcinoma. The trial included 123 patients. At data cutoff, 96 patients had disease progression, and results were similar across the two arms, with a median progression-free survival of 6.77 months in patients on the onartuzumab arm vs 6.97 months for those on the placebo arm. In MET-positive patients, progression-free survival was 5.95 months for patients receiving onartuzumab vs 6.8 months for those in the placebo arm. Serious adverse events also occurred more frequently in patients on onartuzumab (55% vs 40%). Photo by © ASCO/Todd Buchanan 2015.[12]
References: 

1. Chen L-T, Von Hoff DD, Li C-P, et al. Expanded analyses of napoli-1: Phase 3 study of MM-398 (nal-IRI), with or without 5-fluorouracil and leucovorin, versus 5-fluorouracil and leucovorin, in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy. 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 234.

2. Smith JJ, Chow OS, Eaton A, et al. Organ preservation in patients with rectal cancer with clinical complete response after neoadjuvant therapy. 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 509.

3. Zhu AX, Ryoo B-Y, Yen C-J, et al. Ramucirumab (RAM) as second-line treatment in patients (pts) with advanced hepatocellular carcinoma (HCC): Analysis of patients with elevated α-fetoprotein (AFP) from the randomized phase III REACH study. 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 232.

4. Kwak EL, LoRusso P, Hamid O, et al. Clinical activity of AMG 337, an oral MET kinase inhibitor, in adult patients (pts) with MET-amplified gastroesophageal junction (GEJ), gastric (G), or esophageal (E) cancer. 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 1.

5. Mariette C, Meunier B, Pezet D, et al. Hybrid minimally invasive versus open oesophagectomy for patients with oesophageal cancer: A multicenter, open-label, randomized phase III controlled trial, the MIRO trial. 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 5.

6. Cremolini C, Loupakis F, Masi G, et al. FOLFOXIRI plus bevacizumab (bev) versus FOLFIRI plus bev as first-line treatment of metastatic colorectal cancer (mCRC): Updated survival results of the phase III TRIBE trial by the GONO group. 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 657.

7. Muro K, Bang Y-J, Shankaran V, et al. Relationship between PD-L1 expression and clinical outcomes in patients (Pts) with advanced gastric cancer treated with the anti-PD-1 monoclonal antibody pembrolizumab (Pembro; MK-3475) in KEYNOTE-012. 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 3.

8. Penniment MG. Full report of the TROG 03.01, NCIC CTG ES2 multinational phase III study in advanced esophageal cancer comparing palliation of dysphagia and quality of life in patients treated with radiotherapy or chemoradiotherapy. 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 6.

9. Ng K, Venook AP, Sato K, et al. Vitamin D status and survival of metastatic colorectal cancer patients: Results from CALGB/SWOG 80405 (Alliance). 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 507.

10. Phan AT, Caplin ME, Pavel ME, et al. Effects of lanreotide autogel/depot (LAN) in pancreatic neuroendocrine tumors (pNETs): A subgroup analysis from the CLARINET study. 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 233.

11. Tabernero J, Cohn AL, Obermannova R, et al. RAISE: A randomized, double-blind, multicenter phase III study of irinotecan, folinic acid, and 5-fluorouracil (FOLFIRI) plus ramucirumab (RAM) or placebo (PBO) in patients (pts) with metastatic colorectal carcinoma (CRC) progressive during or following first-line combination therapy with bevacizumab (bev), oxaliplatin (ox), and a fluoropyrimidine (fp). 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 512.

12. Shah MA, Cho JY, Tan IB, et al. Randomized phase II study of FOLFOX +/- MET inhibitor, onartuzumab (O), in advanced gastroesophageal adenocarcinoma (GEC). 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 2.

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