CHICAGO -- Treatment with an investigational antibody led to extended remissions and longer survival for patients with advanced gastric cancers, a researcher said here.
In a phase II randomized trial, adding IMAB362 to standard chemotherapy increased progression-free survival (PFS) and overall survival (OS) by about 50% compared with the standard treatment alone, according to , of the Krankenhaus Nordwest-University Cancer Center in Frankfurt, Germany.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
And among patients with high levels of the target molecule, a cell surface protein called claudin18.2, outcomes were even better, Al-Batran told reporters at the American Society of Clinical Oncology annual meeting.
IMAB362 is the first antibody to target , which is abundant in gastric tumors, Al-Batran said. And, unlike the trials for many new molecules, the FAST trial enrolled patients who had not had previous chemotherapy despite having advanced, locally advanced, or metastatic disease.
The study is important because current treatments usually have poor outcomes, commented ASCO spokesperson MD, of University Hospitals in Cleveland, who moderated the ASCO press conference.
"The median survival in multiple regimens for metastatic gastric cancer is less than a year," she told reporters.
One key aspect of the study is that the claudin 18.2 target occurs in about half the patients, suggesting the therapy "could apply to many patients."
The claudin18.2 molecule plays a role in cell adhesion and intercellular communication, but in tumors, claudin18.2 loses its primary role because the cancers disrupted the tight junctions between cells.
But when the antibody binds to tumor cells expressing the molecule, it causes antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity and kills the cell, Al-Batran told MedPage Today.
The FAST investigators randomized 161 patients with advanced gastric or gastroesophageal junction adenocarcinoma and evidence that their tumors expressed claudin 18.2.
The patients in the control arm got a standard chemotherapy regimen of epirubicin (Ellence), oxaliplatin (Eloxatin), and capecitabine (Xeloda), while those in the treatment arm got IMAB362 in addition to standard treatment.
A third arm, added later, offered the standard chemotherapy combined with a higher dose of IMAB362, but Al-Batran did not report data on those patients.
The primary endpoint of the study was PFS, but the investigators also looked at OS, response rates, and safety.
Among all patients, the investigators found median PFS as 4.8 months in the control arm and 7.9 months in the antibody arm, for a hazard ratio of 0.47, which was significant (P=0.0001).
Also, median OS was 8.4 months in the control arm and 13.2 months in the treatment arm (HR 0.51, P=0.0001).
Among patients with high expression of claudin 18.2, median OS was even better, Al-Batran reported: 9.6 months in the control arm and 16.7 months in the treatment arm, which was significant ( P≤0.0005).
The investigators also found patients getting the antibody were more likely to have a response: eight complete responses and 22 partial responses, compared with three and 18, respectively, in the control arm.
On the other hand, the clinical benefit rate was 64% in both arms because of an increased proportion of stable disease in the control arm. Fewer patients getting the antibody had progressive disease at four versus 10 patients, respectively.
The antibody regimen was generally as well tolerated as the standard chemotherapy alone, Al-Batran reported, with important differences in grades 3 and 4 neutropenia and all grades of vomiting.
The trial justifies moving to a phase III trial, which is in the planning stages, he said.
Disclosures
Al-Batran disclosed relevant relationships with Celgene, Lilly, Merck, Roche, Nordic Bioscience, Hospira, Medac, Novartis, Roche Pharma AG, Vifor Pharma.
Primary Source
American Society of Clinical Oncology
Al-Batran SE, et al "FAST: An international, multicenter, randomized, phase II trial of epirubicin, oxaliplatin, and capecitabine (EOX) with or without IMAB362, a first-in-class anti-CLDN18.2 antibody, as first-line therapy in patients with advanced CLDN18.2+ gastric and gastroesophageal junction (GEJ) adenocarcinoma" ASCO 2016; Abstract LBA4001.