Long-term results from NRG-GI002: A phase II clinical trial platform using total neoadjuvant therapy (TNT) in locally advanced rectal cancer (LARC).

Authors

Thomas George

Thomas J. George

University of Florida Health Cancer Center, Gainesville, FL;

Thomas J. George , Greg Yothers , Osama E. Rahma , Theodore S. Hong , Marcia McGory Russell , Y. Nancy You , William Parker , Samuel A. Jacobs , Peter C. Lucas , Linda H. Colangelo , Marc J Gollub , William A. Hall , Lisa A. Kachnic , Madhuri Bajaj , Howard M. Gross , Richard A. Peterson , Jennifer Anne Dorth , Namrata Vijayvergia , Norman Wolmark

Organizations

University of Florida Health Cancer Center, Gainesville, FL; , University of Pittsburgh Department of Biostatistics, Pittsburgh, PA; , Dana-Farber/Harvard Cancer Institute, Boston, MA; , Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA; , David Geffen School of Medicine at UCLA; VA Greater Los Angeles Healthcare System, Los Angeles, CA; , University of Texas MD Anderson Cancer Center, Houston, TX; , McGill University Health Centre, Medical Physics Unit, Montreal, QC, Canada; , NSABP Foundation, Inc., Pittsburgh, PA; , UMPC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA; , NSABP Foundation, Inc., Department of Biostatistics, Pittsburgh, PA; , Memorial Sloan Kettering Cancer Center, New York, NY; , Medical College of Wisconsin, Milwaukee, WI; , New York Presbyterian - Columbia, New York, NY; , Illinois CancerCare, P.C. / Hartland NCORP, Peoria, IL; , Dayon NCI Community Oncology Research Program, Englewood, OH; , Health Partners, St. Paul, MN; , University Hospitals Seidman Cancer Center, and Case Western Reserve University Comprehensive Cancer Center LAPS, Cleveland, OH; , Fox Chase Cancer Center, Philadelphia, PA; , UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA;

Research Funding

U.S. National Institutes of Health
U.S. National Institutes of Health, AbbVie, Merck

Background: This NCTN multi-arm randomized phase II modular clinical trial platform utilizes TNT with parallel experimental arms (EAs) in LARC. EAs are not intended for direct comparison, but rather to concurrently randomized control arm (CA) patients. Primary endpoint (EP) and available secondary EPs (from EA1 using veliparib [V], PARPi; and EA2 using pembrolizumab [P], anti-PD-1) have been previously reported. We present long-term outcomes of all pts enrolled (NCT02921256). Methods: Stage II/III pts with MSS LARC (with any ONE of the following: distal location [cT3-4 ≤5cm from anal verge, any N]; bulky [any cT4 or tumor within 3mm of mesorectal fascia]; high risk for metastatic disease [cN2]; or not a sphincter-sparing surgery [SSS] candidate) were randomized to CA (neoadjuvant FOLFOX [x 4mo] → chemoRT [capecitabine with 50.4Gy] → surgery 8-12 wks later). EA1 added V (400mg PO BID) and EA2 added P (200mg IV Q3 wks x 6 doses) each concurrent with chemoRT. Primary EP: 4-point reduction in Neoadjuvant Rectal Cancer (NAR) score with a one-sided α=0.10, 80% power. NAR compared by linear model controlling for clinical T4 at entry (Y/N). Secondary EPs: OS, DFS. p-values are two-sided. Results: From 10/2016-2/2018, 178 pts were randomized (88 CA, 90 EA1). From 8/2018-5/2019, 185 pts were randomized (95 CA, 90 EA2). Baseline characteristics were previously reported. Median follow-up is 3.50 yrs for the 1st comparison. Median follow-up is 3.15 yrs for the 2nd comparison. Updated primary and long-term secondary outcomes are in the table. Conclusions: With longer follow-up, addition of V to TNT provided no significant differences in the NAR score or 3yr outcomes. The addition of P to TNT was associated with a statistically significant improvement in 3yr OS, but not DFS. Correlative molecular analyses are ongoing. Support: U10CA180868, -180822; UG1-189867; U24-196067; AbbVie; Merck. Clinical trial information: NCT02921256.

First Comparison Outcome NAR scoreCAEA1 (V)StatP-value (*Logrank)
Mean 12.5
95% CI
(9.7, 15.2)
Mean 13.3
95% CI
(10.1, 16.5)
Mean Diff -0.8
95% CI
(-5.0, 3.3)
0.81
3yr DFS67%
29 events
60%
38 events
HR=1.36
95% CI (0.83, 2.25)
0.23*
3yr OS92%
7 deaths
85%
14 deaths
HR=2.13
95% CI (0.86, 5.29)
0.10*
Second Comparison Outcome NAR scoreCAEA2 (P)StatP-value (*Logrank)
Mean 14.4
95% CI
(11.1, 17.7)
Mean 11.5
95% CI
(8.5, 14.5)
Mean Diff 2.9
95% CI (-1.6, 7.3)
0.21
3yr DFS64%
33 events
64%
31 events
HR=0.95
95% CI (0.58, 1.55)
0.82*
3yr OS87%
13 deaths
95%
6 deaths
HR=0.35
95% CI (0.12, 1.00)
0.04*

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Abstract Details

Meeting

2023 ASCO Gastrointestinal Cancers Symposium

Session Type

Oral Abstract Session

Session Title

Oral Abstract Session C: Cancers of the Colon, Rectum, and Anus

Track

Colorectal Cancer,Anal Cancer

Sub Track

Therapeutics

Clinical Trial Registration Number

NCT02921256

Citation

J Clin Oncol 41, 2023 (suppl 4; abstr 7)

DOI

10.1200/JCO.2023.41.4_suppl.7

Abstract #

7

Abstract Disclosures

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