Meeting
2019 ASCO Annual Meeting
CCTG CO.26: Updated analysis and impact of plasma-detected microsatellite stability (MSS) and tumor mutation burden (TMB) in a phase II trial of durvalumab (D) plus tremelimumab (T) and best supportive care (BSC) versus BSC alone in patients (pts) with refractory metastatic colorectal carcinoma (rmCRC).
Authors
Eric Xueyu Chen
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Eric Xueyu Chen , Derek J. Jonker , Jonathan M. Loree , Hagen F. Kennecke , Scott R. Berry , Felix Couture , Chaudhary E. Ahmad , John R. Goffin , Petr Kavan , Mohammed Harb , Bruce Colwell , Setareh Samimi , Benoit Samson , Tahir Abbas , Nathalie Aucoin , Francine Aubin , Sheryl L. Koski , Alice Chia-chi Wei , Dongsheng Tu , Christopher J. O'Callaghan
Organizations
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada, BC Cancer, Vancouver, BC, Canada, Virginia Mason Hospital and Medical Center, Seattle, WA, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, Centre Hospitalier Universitaire de Québec, Quebec City, QC, Canada, Newfoundland Cancer, St John's, NL, Canada, Juravinski Cancer Centre, Burlington, ON, Canada, McGill University, Montreal, QC, Canada, Moncton Hospital, Moncton, NB, Canada, Nova Scotia Cancer Center, Halifax, NS, Canada, University of Montreal Sacre Coeur Hospital, Montreal, QC, Canada, Hopital Charles-LeMoyne, Quebec, QC, Canada, Saskatoon Cancer Centre, Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon, SK, Canada, Hôpital Cité de la Santé de Laval, Laval, QC, Canada, Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, QC, Canada, Cross Cancer Institute, Edmonton, AB, Canada, University of Toronto, Toronto, ON, Canada, Queen's University, Canadian Cancer Trials Group, Kingston, ON, Canada
Research Funding
Other Foundation
Pharmaceutical/Biotech Company
Background: Targeting both PD-L1 and CTLA-4 may be synergistic immunotherapy approaches. CO.26 evaluated if dual inhibition leads to improved pt survival vs BSC alone in rmCRC. Methods: rmCRC pts were randomized 2:1 to D+T vs BSC. Treatment consisted of D (1500 mg) D1 q 28 days and T (75 mg) D1 for first 4 cycles, and supportive measures. Primary endpoint was overall survival (OS). Two-sided p < 0.10 was considered statistically significant. Cell-free (cf)DNA sequencing for MSI and TMB used GuardantOMNI panel and baseline plasma. Results: From 08/2016-06/2017, 180 pts were enrolled. Pt characteristics were balanced between arms. At median follow-up of 15.2 months (mos), median OS was 6.6 mos for D+T and 4.1 mos for BSC (p = 0.07; Hazard ratio (HR): 0.72, 90% confidence interval (CI): 0.54 – 0.97). Progression free survival (PFS) was 1.8 mos vs 1.9 mos, respectively (HR 1.01, 90% CI 0.76 – 1.34). Disease control rate (DCR) was 22.6% for D+T and 6.6% for BSC (p = 0.006). cfDNA analysis was successful in 168/169 pts (99.4%). Two pts were MSI-high. In 166 MSS pts, OS HR was 0.66 (p=0.024; 90% CI 0.49-0.89). Excluding the MSI-H cases (TMB of 74.7 and 247.1 mts/Mb), mean TMB was 20.4 ± 16.3 mts/Mb (range: 0.96 – 114.0). In MSS pts, a pre-specified cutpoint of 20 mts/Mb stratified pts into high and low TMB groups but was not predictive for OS , PFS, or DCR (interaction p-values > 0.7). Using a minimum p-value approach, pts with TMB >28 mts/Mb (21% of MSS pts) had the greatest OS benefit (HR 0.34, 90% CI 0.18-0.63) for D+T (interaction p = 0.07). High TMB was associated with a trend in worse prognosis for OS in the BSC arm using both 20 mts/Mb (HR 1.26, 90% CI 0.76-2.12) and 28 mts/Mb (HR 2.59 90% CI 1.46-4.62) cutpoints. Conclusions: D+T significantly prolonged OS in pts with rmCRC. High TMB may select a group of MSS pts who benefit from D+T. Plasma TMB appeared prognostic in the BSC arm. This is the first study showing combined PD-L1 and CTLA-4 inhibition prolongs survival in pts with MSS rmCRC. Updated results based on deaths in more than 90% of pts will be presented. Clinical trial information: NCT02870920
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Abstract Details
Session Type
Poster Discussion Session
Session Title
Gastrointestinal (Colorectal) Cancer
Track
Gastrointestinal Cancer—Colorectal and Anal
Sub Track
Colorectal Cancer–Advanced Disease
Clinical Trial Registration Number
NCT02870920
Citation
J Clin Oncol 37, 2019 (suppl; abstr 3512)
DOI
10.1200/JCO.2019.37.15_suppl.3512
Abstract #
3512
Poster Bd #
4
Abstract Disclosures
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