McGovern, D.

Objectives This analysis investigated nomogram use to evaluate metastatic pancreatic cancer prognosis. Methods Thirty-four baseline factors were examined in the Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT) (nab-paclitaxel plus gemcitabine vs gemcitabine) data set. Factors significantly (P < 0.1) associated with overall survival (OS) in a univariable model or with known clinical relevance were tested further. In a multivariable model, factors associated with OS (P < 0.1) were selected to generate the primary nomogram, which was internally validated using bootstrapping, a concordance index, and calibration plots. Results Using data from 861 patients, 6 factors were retained (multivariable analysis): neutrophil-lymphocyte ratio, albumin level, Karnofsky performance status, sum of longest diameter of target lesions, presence of liver metastases, and previous Whipple procedure. The nomogram distinguished low-, medium-, and high-risk groups (concordance index, 0.67; 95% confidence interval, 0.65–0.69; median OS, 11.7, 8.0, and 3.3 months, respectively). Conclusions This nomogram may guide estimates of the range of OS outcomes and contribute to patient stratification in future prospective metastatic pancreatic cancer trials; however, external validation is required to improve estimate reliability and applicability to a general patient population. Caution should be exercised in interpreting these results for treatment decisions: patient characteristics could differ from those included in the nomogram development.

4109 Background: Prognostic nomograms have been developed in various cancers, including ovarian, breast, and gastrointestinal; however, there is limited information on nomograms in MPC. The large, phase 3 MPACT study of nab-P + Gem vs Gem alone for the treatment of MPC provides a robust database for the development of a nomogram to predict OS using baseline patient variables. Methods: A multivariable Cox model was created from MPACT data using factors that were significantly predictive of OS in univariable analysis or considered clinically important (stepwise selection to remain in model). From the Cox model, a nomogram was derived that assigned points equal to the weighted sum of relative significance of each variable. The nomogram was internally validated using bootstrapping, a concordance index (c-index), and calibration plots. Results: Data from all 861 pts were used. Seven of the 34 considered variables were retained in the multivariable analysis (Table; all factors significant at the P < 0.01 level, except for analgesic use [ P = 0.07]). The resulting nomogram was able to distinguish low (n = 216), medium (n = 430), and high (n = 215) risk groups (c-index: 0.69; CI: 0.67-0.71) with median OS values of 12.9, 8.2, and 3.7 months, respectively. Calibration curves showed that the nomogram’s predicted probabilities were mostly consistent with observed probabilities for 6-, 9-, and 12-month OS. Conclusions: Treatment arm, Karnofsky performance status (KPS), neutrophil-to-lymphocyte ratio (NLR), albumin level, sum of longest tumor diameters (SLD), and presence of liver metastasis were the key predictors of OS. This nomogram, which will be presented in visual format in the final presentation, may help physicians and pts make informed treatment decisions. Clinical trial information: NCT00844649. [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.

TPS474 Background: In pts with APC, the distal common bile duct is frequently obstructed, which can lead to elevated bilirubin levels. Normalization of bilirubin by stenting can take weeks, so treatment options that could be initiated in pts with elevated bilirubin are desirable. In a phase III trial of pts with metastatic PC, nab-P + Gem demonstrated superior efficacy vs Gem alone for all endpoints, including overall survival (OS; median, 8.7 vs 6.6 months; hazard ratio, 0.72; P < 0.001). This study will be the first to analyze safety and PK profiles of nab-P + Gem in pts with APC and CH secondary to bile duct obstruction. Methods: Treatment-naive pts (≈ 12 to 40) with APC, Karnofsky performance status ≥ 70, and CH due to bile duct obstruction are eligible. Pts with a biliary stent must have 2 stable (within 20% of each other) bilirubin readings within 48 to 72 hours of each other taken between 5 and 21 days after stenting. Exclusion criteria consist of brain metastases, any other active malignancy, infection requiring systemic therapy, a history of myocardial infarction, or current use of medications known to be strong inducers of CYP3A4 and CYP2C8. Pts will enter 1 of 2 cohorts based on bilirubin level: cohort 1, > 1.5 to 3 × upper limit of normal (ULN), or cohort 2, > 3 to 5 × ULN. Cohort 2 will proceed only after review of safety and PK data from cohort 1 by a safety monitoring committee (SMC) and a decision has been made to proceed. The starting doses are nab-P 100 mg/m2 and Gem 800 mg/m2 for cohort 1 and nab-P 75 mg/m2 and Gem 600 mg/m2 for cohort 2. Treatment will be administered on days 1, 8, and 15 of each 28-day cycle. Doses in each cohort will be modified according to tolerability as determined by the SMC. The primary endpoints are determination of maximum tolerated dose for each cohort and PK profile. Secondary endpoints include investigator-assessed objective response rate, progression-free survival, OS, PK profile of Gem, and safety. The exploratory endpoint is change in serum CA19-9 level from baseline. Enrollment is ongoing. ClinicalTrials.gov: NCT02267707. Clinical trial information: NCT02267707.