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Personalized Antibodies for Gastroesophageal Adenocarcinoma (PANGEA): A Phase II Study Evaluating an Individualized
Daniel V T Catenacci1, Stephanie Moya2, Samantha Lomnicki2
1The University of Chicago, Section of Hematology/Oncology, Department of Medicine, Chicago, Illinois. dcatenac@bsd.uchicago.edu.
Abstract:
The one-year and median overall survival (mOS) rates of advanced gastroesophageal adenocarcinomas (GEA) are ∼50% and <12 months, respectively. Baseline spatial and temporal molecular heterogeneity of targetable alterations may be a cause of failure of targeted/immunooncologic therapies. This heterogeneity, coupled with infrequent incidence of some biomarkers, has resulted in stalled therapeutic progress. We hypothesized that a personalized treatment strategy, applied at first diagnosis then serially over up to three treatment lines using monoclonal antibodies combined with optimally sequenced chemotherapy, could contend with these hurdles. This was tested using a novel clinical expansion-platform type II design with a survival primary endpoint. Of 68 patients by intention-to-treat, the one-year survival rate was 66% and mOS was 15.7 months, meeting the primary efficacy endpoint (one-sided P = 0.0024). First-line response rate (74%), disease control rate (99%), and median progression-free survival (8.2 months) were superior to historical controls. The PANGEA strategy led to improved outcomes warranting a larger randomized study. SIGNIFICANCE: This study highlights excellent outcomes achieved by individually optimizing chemotherapy, biomarker profiling, and matching of targeted therapies at baseline and over time for GEA. Testing a predefined treatment strategy resulted in improved outcomes versus historical controls. Therapeutic resistance observed in correlative analyses suggests that dual targeted inhibition may be beneficial.This article is highlighted in the In This Issue feature, p. 211.
Insights
A personalized treatment strategy for advanced gastroesophageal adenocarcinoma (GEA) improved survival rates. This approach, combining chemotherapy and targeted therapies, offers new hope for GEA patients.
Area of Science:
- Oncology
- Gastroenterology
- Clinical Trials
Background:
- Advanced gastroesophageal adenocarcinomas (GEA) have poor prognoses with low survival rates.
- Molecular heterogeneity and infrequent biomarkers hinder targeted and immunooncologic therapies.
- Stalled therapeutic progress necessitates novel treatment strategies for GEA.
Purpose of the Study:
- To test a personalized, serial treatment strategy for advanced GEA.
- To evaluate the efficacy of combining monoclonal antibodies with sequenced chemotherapy.
- To address molecular heterogeneity and improve patient outcomes in GEA.
Main Methods:
- A novel clinical expansion-platform type II design was employed.
- The strategy involved personalized treatment at diagnosis and serially over three lines.
- Monoclonal antibodies were combined with optimally sequenced chemotherapy.
Main Results:
- One-year survival rate was 66% and median overall survival (mOS) was 15.7 months.
- First-line response rate was 74%, disease control rate 99%, and median progression-free survival 8.2 months.
- Outcomes surpassed historical controls, meeting the primary efficacy endpoint.
Conclusions:
- The PANGEA strategy demonstrated improved outcomes for advanced GEA.
- Individually optimizing chemotherapy, biomarker profiling, and targeted therapy matching is crucial.
- Further randomized studies are warranted, with potential for dual targeted inhibition.
