Patient Selection Key in Managing Gastrointestinal Tumors

Liam Davenport

July 05, 2017

BARCELONA — Patients with gastrointestinal tumors should be assessed for the presence of protein biomarkers and clinical factors, such as renal impairment, before receiving chemotherapy, conclude experts summarizing a series of studies.

In a wide-ranging discussion of abstracts and posters presented here at the 19th World Congress on Gastrointestinal Cancer (WCGC), two experts discussed the implications for real-world oncologic practice of novel data on gastric cancer and colorectal cancer (CRC), finding that patient selection remains a key part of achieving successful outcomes.

Chris Verslype, MD, PhD, University Hospital Gasthuisberg, Leuven, Belgium, began the session with a discussion of new findings in gastric cancer.

These come from a new analysis of data from the negative Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S) trial, reported in poster PD007, by a group led by Fabiola Cecchi from NantOmics, Rockville, Maryland, and colleagues from the University of Chicago, Illinois, and the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

This study looked at the survival outcomes of patients with radically resected gastric cancer who were treated with the intensive regimen of FOLFIRI (leucovorin [LV], irinotecan, and fluorouracil [5-FU])  followed by the combination of docetaxel and cisplatin, and how this compared to outcomes in patients who received only 5-FU and  LV.

The main results from this study showed no survival advantage for the more intensive chemotherapy regimen.

The new analysis, now reported at the meeting, examined archived tumor samples from patients who participated in this study. The samples were examined for protein biomarkers by using multiplexed mass spectrometry proteomic analysis, with particular interest in two biomarkers: levels of class III β-tubulin (TUBB3) protein (a potential marker of taxane resistance) and thymidine phosphorylase (TYMP; a marker of response to 5-FU).

The researchers found that among patients treated with the intensified regimen, median overall survival was almost twice as long in those with low TUBB3 expression (<750 amol/µg) than in those with higher levels of expression (P = .033), while no association was seen in patients given 5-FU/LV.

Among the patients treated with the less intensive 5-FU/LV regimen, levels of the TYMP protein greater than 1335 amol/µg were associated with a more than doubling of median overall survival.

The longest survival was seen in patients receiving the intensified regimen who had both low TUBB3 and high TYMP expression.

These findings are "very important," Dr Verslype said: "Reanalyzing an existing trial with some biomarkers has shed a new light on this therapy."

New Findings in CRC

Next at the meeting, Ali Shamseddine, MD, American University of Beirut Medical Center, Lebanon, highlighted several abstracts on colorectal cancer .

Among these, poster PD029 examined whether bevacizumab (Avastin, Genentech) is safe to use in patients with advanced CRC who have a malignant bowel obstruction and have received a self-expandable stent (SEMS) rather than undergoing surgery.

The investigators, led by V Pacheco-Barcia, from the Servicio Oncología Médica at the Hospital La Princesa, Madrid, Spain, retrospectively analyzed the medical records of 75 patients who were treated between 2012 and 2015.

They found that  SEMS placement was associated with high technical and clinical success rates and a median potency of 12.7 months.

However, Dr Shamseddine noted that complications, including perforation, reobstruction, bleeding, and migration, were seen in 29% of the cohort, with a significant increase in complications in patients with stage IV disease (HR, 2.8; P = .04).

Of greater significance, however, was that the rate of perforations was significantly higher among patients treated with bevacizumab than among other patients, at 20% vs 5%, respectively (P = .13).

Dr Shamseddine said that although the results show that the SEMS "is effective in obstruction, lasting for more than a year," clinicians should "keep in mind" the high overall complication rate and the high incidence of perforation with bevacizumab.

Another abstract highlighted by Dr Shamseddine was poster PD021, which focused on the clinical impact of renal impairment in elderly patients with colon cancer who received capecitabine plus oxaliplatin (CapeOx) as adjuvant therapy.

This was a retrospective, multicenter, postmarketing surveillance study in 189 patients, reported by Yamazaki Kentaro from the Shizuoka Cancer Center, Sunto-gun, Japan, and colleagues.

The participants were at least 65 years of age; 137 patients (72.5%) had a high creatinine clearance (CLcr) (≥50 mL/min), and the remaining 52 patients (27.5%) had a low CLcr (<50 mL/min).

Grade 3 or greater adverse events were recorded in 31.3% of patients with a high CLcr, compared with 42.3% of those with a low CLcr. Frequently reported events were anorexia, diarrhea, hand and foot syndrome, and decreased neutrophil count.

Furthermore, discontinuation of CapeOX within four cycles of therapy due to adverse events was 2.9% among patients with a high CLcr, compared with 21.1% in those with a low CLcr, at an adjusted odds ratio of 11.2 (P = .0008).

Dr Shamseddine said, "The incidence of grade 3/4 toxicity due to CapeOx and early discontinuation due to adverse events in elderly patients with creatine clearance less than 50 mL/min should be taken into consideration, and these patients should be treated cautiously."

19th World Congress on Gastrointestinal Cancer (WCGC).  Highlights Session. Presented June 30, 2017.

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