Citations

348 Background: Patients (pts) with mUC have few treatment options beyond the second-line setting. HER2 gene amplification has been reported in a minority of pts with UC, but there have been anecdotal reports of the activity of HER2-targeted agents. MyPathway is a multi-basket study evaluating the efficacy and safety of targeted therapies in non-indicated tumor types harboring relevant molecular alterations. We present preliminary data for pts with HER2-positive mUC receiving HER2-targeted treatment with pertuzumab + trastuzumab. Methods: MyPathway (NCT02091141) is an open-label, multicenter, phase IIA study. Pts in this subset analysis had refractory mUC with HER2 amplification or putative activating mutations by gene sequencing, FISH, or IHC. Pts received standard doses of pertuzumab + trastuzumab without chemotherapy until disease progression or unacceptable toxicity. The primary endpoint is investigator-assessed overall response rate (RECIST v1.1). Results: As of July 31, 2016, 12 pts with platinum-resistant HER2-positive mUC (HER2-amplified, n=9; HER2-mutated, n=3) have been enrolled. At a median follow-up of 5.4 (range 0.9–14.5) mos, 1 pt had complete response (CR, ongoing at 12.5 mos), 2 had partial responses (PR; duration of response, 3.7 and 5.5 mos), and 2 had stable disease (SD) for >4 mos (Table). Safety was consistent with the product labels. Conclusions: Preliminary results indicate that the combination of pertuzumab + trastuzumab has activity in previously treated HER2-amplified mUC, including a durable CR in a pt with peritoneal metastases. Accrual to MyPathway is ongoing. Clinical trial information: NCT02091141. [Table: see text]

514 Background: Randomized trials and OCSs have demonstrated that BV treatment in 1st-line (1L), in 2L, and across multiple lines is associated with longer survival in patients (pts) with mCRC. This analysis was aimed at comparing the effectiveness of BV after 1st disease progression (PD) between male and female mCRC pts who received 1L BV-containing therapy in a real-world setting. Methods: ARIES is a large, prospective OCS that enrolled pts who received BV and chemotherapy (CT) for 1L mCRC. Post-PD effectiveness was assessed for men and women characterizing BV use by cumulative and dichotomous approaches. The primary analysis treated BV exposure as cumulative BV doses after 1st PD and post-progression overall survival (ppOS) as the time from 1st PD to death. A time-dependent Cox regression model was fitted to assess the effect of cumulative BV exposure on ppOS, while controlling for potential confounders. A dichotomous secondary analysis characterized BV exposure as receipt of CT + BV (BBP) or CT alone (No BBP) within 2 months after PD and ppOS as time from 1st PD + 2 months to death. Results: Among the 1,550 1L mCRC pts enrolled, 1,199 (532 women) had PD. In the primary analysis, hazard ratios (HRs) for ppOS decreased, on average, by 1.2% with each additional BV dose. When stratified by sex, the average risk reduction per BV dose over 15 doses was 1.8% in women and 0.7% in men. In the secondary analysis that included 331 women (BBP, 180; No BBP, 151) and 417 men (BBP, 245, No BBP, 172) who received BV ± CT within 2 months post-PD, the HRs for ppOS with BBP treatment were 0.46 (95% CI, 0.35–0.59) in women and 0.52 (95% CI, 0.41–0.67) in men. Statistical interaction tests for differences in the effectiveness of BV between men and women were negative for primary and secondary analyses (P of 0.58 and 0.77). Protocol-specified adverse events occurred in 17.8% of women and 10.2% of men in the BBP population; this difference was largely related to rates of hypertension (8.3% vs 2.4%, respectively). Conclusions: In ARIES, the effectiveness of BV after first PD was not statistically different between women and men with mCRC. Clinical trial information: NCT00388206.

702 Background: Median overall survival (OS) in mCRC has significantly improved over the past 20 yrs, but the observed range of OS in pts remains wide; a large percentage of pts have OS <1 yr or >4 yrs. ARIES was a prospective OCS conducted from 2006–2012 that evaluated outcomes in pts receiving BV + chemotherapy (CT) for mCRC in general clinical practice. The objective of this analysis is to examine clinical characteristics of pts with long vs short OS. Methods: This analysis included 1,417/1,550 first-line (1L) BV-treated mCRC pts who died or had complete follow-up on study. Long OS was defined as OS within the upper quartile of the analysis population (range 42–67 mos); short OS was defined as OS within the lower quartile (range 0.3–12 mos). Progression-free survival (PFS) was estimated using Kaplan-Meier methods. Pt and disease characteristics and treatment patterns were described using summary statistics. Results: Pt and disease characteristics are shown in the Table. Median PFS was 22.3 mos (95% CI, 19.9–23.3) vs. 4.9 mos (95% CI, 4.6–5.4), in the long-OS vs. short-OS groups. More pts with long OS received any second-line (2L) therapy (71% vs. 46%), and were exposed to 5-fluorouracil, oxaliplatin, and irinotecan throughout the course of their disease (53% vs. 32%) compared with pts with short OS. KRAS/BRAF mutation status was not collected. Conclusions: Pts with long OS had better baseline performance status, primary tumors more likely to have been resected, and were more likely to have received 2L CT. Additional analyses of detailed treatment patterns and safety are ongoing. Clinical trial information: NCT00388206. [Table: see text]

83 Background: Although surgery is traditionally the standard of care for esophageal cancer, esophagectomy carries significant morbidity and mortality. Alternative endoscopic therapies are needed for patients who are not candidates for conventional treatment. The objective of this study was to assess the safety, efficacy, and tolerability of spray cryotherapy of esophageal cancer. Methods: This study includes patients enrolled retrospectively and prospectively in an open-label registry and patients in a retrospective cohort from twelve academic and community practices. Endoscopic spray cryotherapy was performed until local tumor eradication was confirmed by biopsy or until treatment was halted due to progression of disease, patient withdrawal or co-morbidities. Results: One-hundred and eight patients (median age 75.5, 79.6% male, 93.5% adenocarcinoma, mean length 5.2 cm) underwent 442 treatments (mean 4.2 per patient). Tumor stages included 40 with T1a, 27 with T1b, 10 with unspecified T1, 15 with T2, and 16 with no T stage reported. One-hundred and six patients completed treatment with complete response of intraluminal disease in 54.7%, including complete response in 74.4% for T1a, 50% for T1b, 65.3% for all T1, 6.7% for T2, and 50% for those with no T stage reported. Mean follow-up was 17.3 months. There were no deaths or perforations related to spray cryotherapy. Strictures developed in 11 of 108 patients (10.2%) but were present before spray cryotherapy in 3 of 11. Conclusions: This study suggests that endoscopic spray cryotherapy is safe, well tolerated and effective for early esophageal cancer in patients who are not candidates for conventional therapy.

653 Background: Next-generation sequencing often reveals potentially actionable molecular alterations; however, data on approved targeted therapies in non-indicated tumors are limited. MyPathway (NCT02091141) evaluates agents targeting the HER2, EGFR, BRAF, or Hedgehog (Hh) pathways in tumors for which these therapies are not currently indicated. Here, we present early response data for patients with GI tumors. Methods: Eligible patients had metastatic tumors with potentially actionable genomic alterations, identified by a CLIA-certified lab, and progression on standard therapy. Based on the identified alteration, patients received standard doses of trastuzumab + pertuzumab (HER2), erlotinib (EGFR), vemurafenib (BRAF), or vismodegib (Hh). Response was evaluated by the investigator using RECIST v1.1. Results: As of Aug 21, 2015, 96 patients had enrolled, 36 of whom (38%) had GI tumors with the following alterations: HER2 (n=28 [22 amplifications, 5 activating mutations, 1 both]), BRAF (n=4), Hh (n=2 [2 PTCH-1 mutations]), and EGFR (n=2). Patients had a median of 4 (range, 1–8) prior lines of therapy. Tumor types and interim best response data are shown below. Among all evaluable patients with GI tumors (n=26), 5 have had a PR to targeted therapy (duration 3–10+ months). Conclusions: Targetable molecular alterations were found in a variety of GI tumors, resulting in clinical benefit from targeted treatments that would not have otherwise been realized. These early results support this molecular testing strategy. Accrual to the trial continues; based on activity observed, the HER2-positive colorectal cancer cohort will be expanded to ≥30 patients. Additional data will be presented at the meeting. Clinical trial information: NCT02091141. [Table: see text]

535 Background: Prior ARIES analyses showed that BV-treated mCRC patients (pts) receiving chemotherapy (CT)/biologics + BV within 2 months (mo) after 1st progressive disease (PD) had longer post-progression survival (PPS) than pts receiving only CT/biologics. The present analysis evaluated whether this effect of BV was consistent when used with common 2L CT regimens— irinotecan- (iri-) and oxaliplatin- (ox-) based—in mCRC pts exposed to 1L BV in ARIES. Methods: ARIES enrolled mCRC pts receiving 1L CT + BV. No tx regimens or assessments were protocol specified. This analysis evaluated 1L BV-treated mCRC pts who had PD, survived ≥2 mo after PD, and received 2L iri- or ox-based tx. PPS was estimated by Kaplan-Meier methods. Cox regression was used to estimate hazard ratios (HRs), while adjusting for covariates (eg, 1L time to progression). Results: Of 1550 1L pts in ARIES, 1074 had 1st PD and survived ≥2 mo after PD. Of these 1074, 390 and 114 received 2L iri- and ox-based tx, respectively, ± BV ( table ). Baseline characteristics were generally similar between groups. The incidence of targeted adverse events (TAEs) was as expected and similar between the BV and No BV groups over time. In pts receiving 2L iri- or ox-based CT tx, PPS in BV-treated pts was longer compared to those not on BV. Analyses may be limited by small pt numbers in some groups. Conclusions: Consistent with prior ARIES analyses, the continued use of BV after 1st PD was associated with prolonged PPS regardless of the 2L CT backbone used. [Table: see text]

Abstract Purpose The aim of this study was to investigate whether progression-free survival (PFS) can be considered a surrogate endpoint for overall survival (OS) in malignant mesothelioma. Materials and Methods Individual data were collected from 15 Cancer and Leukemia Group B (615 patients) and 2 North Central Cancer Treatment Group (101 patients) phase II trials. The effects of 5 risk factors for OS and PFS, including age, histology, performance status (PS), white blood cell count, and European Organisation for Research and Treatment of Cancer (EORTC) risk score, were used in the analysis. Individual-level surrogacy was assessed by Kendall’s tau through a Clayton bivariate Copula survival (CBCS) model. Summary-level surrogacy was evaluated via the association between logarithms of the hazard ratio (log HR)—log HROS and log HRPFS—measured in R2 from a weighted least-square (WLS) regression model and the CBCS model. Results The median PFS for all patients was 3.0 months (95% confidence interval [CI], 2.8–3.5 months) and the median OS was 7.2 months (95% CI, 6.5–8.0 months). Moderate correlations between PFS and OS were observed across all risk factors at the individual level, with Kendall’s tau ranging from 0.46 to 0.47. The summary-level surrogacy varied among risk factors. The Copula R2 ranged from 0.51 for PS to 0.78 for histology. The WLS R2 ranged from 0.26 for EORTC and PS to 0.67 for age. Conclusions The analyses demonstrated low to moderate individual-level surrogacy between PFS and OS. At the summary level, the surrogacy between PFS and OS varied significantly across different risk factors. With a short postprogression survival and a moderate correlation between PFS and OS, there is no evidence that PFS is a valid surrogate endpoint for OS in malignant mesothelioma.

Key PointsThe monotypic and polytypic PC compartments assessed by MFC are prognostic in AL amyloidosis. MFC may play a role in the definition of hematologic response to treatment.