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
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 score | CA | EA1 (V) | Stat | P-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 DFS | 67% 29 events | 60% 38 events | HR=1.36 95% CI (0.83, 2.25) | 0.23* |
3yr OS | 92% 7 deaths | 85% 14 deaths | HR=2.13 95% CI (0.86, 5.29) | 0.10* |
Second Comparison Outcome NAR score | CA | EA2 (P) | Stat | P-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 DFS | 64% 33 events | 64% 31 events | HR=0.95 95% CI (0.58, 1.55) | 0.82* |
3yr OS | 87% 13 deaths | 95% 6 deaths | HR=0.35 95% CI (0.12, 1.00) | 0.04* |
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Abstract Disclosures
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