Georgoulias, Vassilis

4004 Background: In overall population, IDEA pooled analysis did not demonstrate non-inferiority (NI) regarding 3y DFS in pts with stage III CC receiving 3m vs. 6m of adj FOLFOX/CAPOX. However, in pts treated with CAPOX (especially in low-risk pts), 3m of therapy was as effective as 6m. Results of OS and 5y DFS are reported. Methods: OS was defined as time from enrollment to death due to all causes. OS NI margin was conservatively set to be Hazard Ratio (HR) = 1.11, which is equivalent to: the maximum acceptable loss of OS efficacy, by shortening treatment to 3m, was half of the OS efficacy gained in MOSAIC trial (i.e., 2.26% absolute reduction in 5y OS rate). Pre-planned sub-group analyses included by regimen and risk group for both OS and 5y DFS. NI was to be declared if the one-sided false discovery rate adjusted (FDRa) NI p-value < 0.025. Results: With an overall median survival follow-up of 72 m (range per study, 62 to 84 m), 2584 deaths and 3777 DFS events among 12,835 pts from six trials were observed. Across 6 studies, 39.5% of pts received CAPOX (rate by study, 0% to 75.1%). Overall, the 5y OS rate was 82.4% (3m) and 82.8% (6m), with estimated OS HR of 1.02 (95% confidence interval [CI], 0.95-1.11; FDRa NI p, 0.058) and absolute 5-y OS rate difference of -0.4% (95% CI, -2.1 to 1.3%). Overall, the 5y DFS rate was 69.1% (3m) and 70.8% (6m), with estimated DFS HR of 1.08 (95%CI, 1.01-1.15, FDRa NI p, 0.22). HRs (95% CI) within subgroups see table. Conclusions: 5y OS rate reported in IDEA trials was higher than historical rates, regardless of duration of therapy. While overall survival in IDEA did not meet prior statistical assumptions for NI in overall population, the 0.4% difference in 5y OS should be placed in clinical context. OS and 5y DFS results continue to support the use of 3m adjuvant CAPOX for the vast majority of stage III colon cancer pts. This conclusion is strengthened by the substantial reduction of toxicities, inconveniencies and cost associated with shorter treatment duration. Clinical trial information: NCT01150045; 2009-010384-16; NCT00749450; ISRCTN59757862; 2007-003957-10; UMIN000008543; 2007-000354 . [Table: see text]

Abstract Introduction Circulating tumor cells (CTCs) have been shown to be prognostic in patients (pts) with metastatic breast cancer (MBC) (Pukazhendhi, Gluck, J Carcinog. 2014). The tnAcity trial evaluated the efficacy/safety of 3 chemotherapy combination regimens (nab-P/carboplatin [C], nab-P/gemcitabine [G], or G/C) as first-line treatment for pts with mTNBC. nab-P/C resulted in a significantly longer PFS & numerically higher ORR vs nab-P/G or G/C (Yardley. SABCS 2016; manuscript in process). CTC levels were assessed at baseline (BL) & during treatment to determine correlation with clinical benefit. Methods Pts with pathologically confirmed mTNBC & no prior cytotoxic chemotherapy for MBC received (1:1:1) nab-P 125 mg/m2 with C area under the curve (AUC) 2, nab-P 125 mg/m2 with G 1000 mg/m2, or G 1000 mg/m2 with C AUC 2, all given d1 & 8 q3w. Primary endpoint: investigator-assessed PFS. Secondary endpoints included ORR & OS; CTC enumeration was a prespecified exploratory objective. CTC levels, assessed (CELLSEARCH®) at BL & start of cycles 3 & 5 (post-BL), were grouped as follows: 0 CTCs/7.5 mL blood at BL (−−), ≥ 1 CTCs/7.5 mL blood at BL & post-BL (++), & ≥ 1 CTCs/7.5 mL blood at BL & clearance of CTCs in ≥ 1 post-BL measurement (+−). Results In total, 126 pts were included: 48, 24, & 54 in the −−, ++, & +− groups, respectively. Mean BL CTC levels for the ++ & +− groups were 55 & 66 CTCs/7.5 mL blood. Pts with BL CTCs of ≥ 1 vs 0 had numerically similar median PFS (7.0 vs 5.9 mo; HR 1.45 [95% CI 0.93 - 2.25]) & OS (15.0 vs 16.0 mo; HR 0.90 [95% CI 0.57 - 1.42]) & higher ORR (64% vs 44%). Mean cycle 3 & 5 CTC levels in the ++ group were 17 & 111 CTCs/7.5 mL blood. Pts in the −− & +− groups had longer PFS vs the ++ group (median 5.9, 8.5, & 4.7 months). Similar improvements in OS & ORR were noted (Table). Conclusions Absence of CTCs at BL & during treatment & clearance of CTCs from BL at least once during treatment were generally associated with improved efficacy outcomes in pts with mTNBC treated with combination chemotherapy. Table. Outcomes by Change in CTC Level from BaselineGroupOutcome−− n = 48+− n = 54++ n = 24PFS, median, mo HR (95% CI)5.9 0.60 (0.34-1.06)a8.5 0.30 (0.17-0.54)a4.7OS, median, mo HR (95% CI)16.0 0.40 (0.22-0.73)a17.8 0.35 (0.20-0.62)a9.8ORR, %43.879.629.2CR6.316.74.2PR37.563.025.0SD35.420.454.2PD16.7—16.7NE4.2——CR, complete response; HR, hazard ratio; NE, not evaluable; ORR, overall response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease. a vs ++ group. Citation Format: Minetta C. Liu, Wolfgang Janni, Vassilis Georgoulias, Denise A. Yardley, Nadia Harbeck, Xin Wei, Desmond McGovern, Robert Beck. First-line doublet chemotherapy for mTNBC: circulating tumor cell analysis of the tnAcity trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4209.