Citations

4006 Background: Lymph node (LN) metastasis is associated with decreased survival in rectal cancer. It has been suggested that at least 14 LN be evaluated for adequate staging. However, a large percentage of patients have fewer than the recommended number of LN examined. We hypothesized that LN ratio would be predictive of overall survival in rectal cancer. Methods: Data was analyzed from Intergroup 0114, a mature trial of postoperative adjuvant chemotherapy and radiation in T3/4 and/or LN positive rectal cancer. Survival was the same for all arms allowing the entire group to be considered as one. The primary endpoint evaluated was overall survival. A proportional hazards model was used to determine the relative prognostic impact of LN ratio compared to number of LN examined, number of positive LN, number of negative LN and AJCC nodal stage. LN ratio was defined as the number of positive LN divided by the total number of LN examined. Four groups were analyzed based on proportion of positive LN: =0.25, >0.25–0.50, >0.50–0.75 and >0.75. Results: 1,648 patients were evaluable. There were 251 T1/2, 1,251 T3 and 146 T4 tumors. 513 patients were N0, 743 N1 and 392 N2. Median number of LN was 9. LN ratio was predictive of 5-year overall survival with rates of 0.71, 0.56, 0.50 and 0.43 respectively when analyzed by quartile (p<0.0001). LN ratio remained significant when overall survival was analyzed by number of LN examined and grouped into <10, <15 and >15 nodes evaluated (p<0.0001 for all). LN ratio also predicted overall survival in N1 (p=0.04) and N2 (p=0.0002) disease. When comparing LN ratio (χ2=79.5, p<0.0001) to number of LN examined (χ2=4.7, p=0.03), number of positive LN (χ2=38, p<0.0001), number of negative LN (χ2=32, p<0.0001) and AJCC nodal stage (χ2=55.5, p<0.0001), LN ratio appears to be the strongest predictor of overall survival. Conclusion: LN ratio predicts overall survival in patients with resected rectal cancer. Importantly, this is true in patients who have had a small number of LN evaluated, in addition to those with a large number of LN examined. LN ratio also appears to be a stronger predictor of overall survival than other described LN prognostic factors. LN ratio may be a useful variable to stratify outcome in patients with node-positive rectal cancer. No significant financial relationships to disclose.

AbstractBackgroundThe 2018 Lipids in Parenteral Nutrition summit involved a panel of experts in clinical nutrition, lipid metabolism, and pharmacology, to assess the current state of knowledge and develop expert consensus statements regarding the use of intravenous lipid emulsions in various patient populations and clinical settings. The main purpose of the consensus statements is to assist healthcare professionals by providing practical guidance on common clinical questions related to the provision of lipid emulsions as part of parenteral nutrition (PN).MethodsThe summit was designed to allow interactive discussion and consensus development. The resulting consensus statements represent the collective opinion of the members of the expert panel, which was informed and supported by scientific evidence and clinical experience.ResultsThe current article summarizes the key discussion topics from the summit and provides a set of consensus statements designed to complement existing evidence‐based guidelines. Lipid emulsions are a major component of PN, serving as a condensed source of energy and essential fatty acids. In addition, lipids modulate a variety of biologic functions, including inflammatory and immune responses, coagulation, and cell signaling. A growing body of evidence suggests that lipid emulsions containing ω‐3 fatty acids from fish oil confer important clinical benefits via suppression of inflammatory mediators and activation of pathways involved in the resolution of inflammation.ConclusionsThis article provides a set of expert consensus statements to complement formal PN guideline recommendations.

Abstract Purpose: Preclinical data demonstrating androgen receptor (AR)–positive (AR+) triple-negative breast cancer (TNBC) cells are sensitive to AR antagonists, and PI3K inhibition catalyzed an investigator-initiated, multi-institutional phase Ib/II study TBCRC032. The trial investigated the safety and efficacy of the AR-antagonist enzalutamide alone or in combination with the PI3K inhibitor taselisib in patients with metastatic AR+ (≥10%) breast cancer. Patients and Methods: Phase Ib patients [estrogen receptor positive (ER+) or TNBC] with AR+ breast cancer received 160 mg enzalutamide in combination with taselisib to determine dose-limiting toxicities and the maximum tolerated dose (MTD). Phase II TNBC patients were randomized to receive either enzalutamide alone or in combination with 4 mg taselisib until disease progression. Primary endpoint was clinical benefit rate (CBR) at 16 weeks. Results: The combination was tolerated, and the MTD was not reached. The adverse events were hyperglycemia and skin rash. Overall, CBR for evaluable patients receiving the combination was 35.7%, and median progression-free survival (PFS) was 3.4 months. Luminal AR (LAR) TNBC subtype patients trended toward better response compared with non-LAR (75.0% vs. 12.5%, P = 0.06), and increased PFS (4.6 vs. 2.0 months, P = 0.082). Genomic analyses revealed subtype-specific treatment response, and novel FGFR2 fusions and AR splice variants. Conclusions: The combination of enzalutamide and taselisib increased CBR in TNBC patients with AR+ tumors. Correlative analyses suggest AR protein expression alone is insufficient for identifying patients with AR-dependent tumors and knowledge of tumor LAR subtype and AR splice variants may identify patients more or less likely to benefit from AR antagonists.

Abstract Background Diabetes is a prognostic factor for some malignancies, but its association with outcome in patients with advanced or metastatic colorectal cancer (CRC) is less clear. Methods This cohort study was nested within a randomized trial of first-line chemotherapy and bevacizumab and/or cetuximab for advanced or metastatic CRC. Patients were enrolled at 508 community and academic centers throughout the National Clinical Trials Network. The primary exposure was physician-documented diabetes at the time of enrollment. The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS) and adverse events. Tests of statistical significance were two-sided. Results Among 2326 patients, 378 (16.3%) had diabetes. The median follow-up time was 6.0 years. We observed 1973 OS events and 2173 PFS events. The median time to an OS event was 22.7 months among those with diabetes and 27.1 months among those without diabetes (HR = 1.27, 95% CI = 1.13 to 1.44; P &lt; .001). The median time to a PFS event was 9.7 months among those with diabetes and 10.8 months among those without diabetes (HR = 1.16, 95% CI = 1.03 to 1.30; P = .02). Patients with diabetes were more likely to experience no less than grade 3 hypertension (8.1% vs 4.4%; P = .054) but were not more likely to experience other adverse events, including neuropathy. Conclusions Diabetes is associated with an increased risk of mortality and tumor progression in patients with advanced or metastatic CRC. Patients with diabetes tolerate first-line treatment with chemotherapy and monoclonal antibodies similarly to patients without diabetes.

Abstract Introduction Ibrutinib has become a new standard of care in patients with previously treated CLL/SLL based on the phase 3 RESONATE study (Byrd, et al. NEJM 2014) and other trials evaluating ibrutinib mainly as a single agent in CLL. The first randomized, double-blind, placebo-controlled phase 3 study (HELIOS) investigating ibrutinib in combination with bendamustine and rituximab (BR) was recently reported (Chanan-Khan, et al. ASCO 2015), with ibrutinib significantly extending progression-free survival and reducing the risk of progression/death by 80%. The study design provides an opportunity to examine the overall safety and management of adverse events (AEs) with ibrutinib and placebo in a blinded manner that previously has not been possible. Here we examine the safety and management of AEs with ibrutinib + BR vs placebo + BR in HELIOS. Methods Patients with active CLL/SLL following ≥ 1 prior line of systemic therapy were randomized 1:1 to receive BR (≤ 6 cycles) with either ibrutinib 420 mg daily or placebo (n = 289 in each group). Safety was a secondary end point. Results Median exposure to ibrutinib and placebo was 14.7 and 12.8 months, respectively. Rates of infection in the ibrutinib + BR and placebo + BR arms were similar (all-grade, 70.4%; grade ≥ 3, 26.8% vs all-grade, 70.0%; grade ≥ 3, 22.6%, respectively) but exposure-adjusted analysis reveals an overall lower rate of infections with ibrutinib + BR vs placebo + BR (10.3/100 vs 11.2/100 patient-months), with similar rates of grade ≥ 3 infections (2.4/100 patient-months each arm). Rates of all-grade (grade 3/4) anemia were 22.3% (3.5%) with ibrutinib + BR and 28.9% (8.0%) with placebo + BR. Patients also required fewer transfusions with ibrutinib + BR (23%) vs placebo + BR (29%), the majority of which were red blood cell transfusions. Similar proportions of patients used growth factors in both arms (54% vs 52%, respectively). Grade 3/4 neutropenia was reported at similar rates in both arms (53.7% vs 50.5%, respectively); however, fewer patients discontinued due to treatment-related neutropenia with ibrutinib + BR (1.0%) vs placebo + BR (2.8%). Rates of thrombocytopenia were slightly higher with ibrutinib + BR (30.7%) than placebo + BR (24.0%), but rates of grade 3/4 events were similar between arms (15.0% each arm). Atrial fibrillation (AF) was observed more frequently in patients on ibrutinib + BR than placebo + BR (7.3% vs 2.8% overall and 2.8% vs 0.7% grade 3/4, respectively). However, only 4 patients with grade 3/4 AF discontinued therapy in the ibrutinib arm. No patients with grade 1/2 AF discontinued treatment. One-third of patients held ibrutinib treatment to manage AF, with all restarting at the same dose (420 mg). Median (range) time to onset was 3.0 (0.3-17.5) months with ibrutinib + BR and 2.4 (0.6-18.9) months with placebo + BR. Importantly, in those with a prior history of AF or abnormal heart rhythm, only 7/25 receiving ibrutinib + BR and 2/22 receiving placebo + BR developed AF/atrial flutter on study. The rates of any-grade bleeding were 31.0% and 14.6%, respectively, with the majority being grade 1 (77.5% and 69.0%, respectively). Low rates of grade 3/4 major bleeding were observed in the ibrutinib + BR (2.1%) and placebo + BR (1.7%) arms. Many patients (41.8% ibrutinib + BR, 41.1% placebo + BR) were receiving concomitant anticoagulant/antiplatelet medication. A low rate of treatment-related lymphocytosis was observed in both arms (7.0% ibrutinib + BR, 5.9% placebo + BR). The majority of cases resolved within 2 weeks. Conclusions In this randomized, double-blind, placebo-controlled trial, the addition of ibrutinib to BR was well tolerated and did not significantly impact the safety profile of BR. In addition, ibrutinib was associated with reduced rates of anemia and transfusional support. Consistent with its known toxicity profile, patients in the ibrutinib + BR arm had higher rates of bleeding (mostly grade 1 or 2) and AF; however, few patients discontinued therapy as a result of these AEs. A prior history of AF or abnormal heart rhythm did not lead to recurrent episodes in the majority of cases. Taken together, the results from HELIOS establish the significant efficacy of ibrutinib and also the overall positive risk-benefit profile of ibrutinib + BR. Disclosures Cramer: Janssen: Other: Travel grant, Research Funding, Speakers Bureau; Hoffman LaRoche: Other: Travel grant, Research Funding, Speakers Bureau; Astellas: Other: Travel grant; Glaxo Smith Klein/Novartis: Research Funding; Gilead: Other: Travel grant, Research Funding; Mundipharma: Other: Travel grant. Demirkan:Celgene: Other: Travel reimbursement; Amgen: Consultancy. Fraser:Hoffman LaRoche: Consultancy, Honoraria; Janssen: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding. Santucci Silva:Janssen: Other: Travel reimbursement, Research Funding; GSK: Research Funding; Celgene: Research Funding; Merck: Research Funding; Novartis: Other: Travel reimbursement; Hoffman LaRoche: Other: Travel reimbursement, Research Funding. Janssens:Roche: Consultancy, Speakers Bureau; Mundipharma: Speakers Bureau; Janssen: Consultancy. Goy:Allos, Biogen Idec, Celgene, Genentech, and Millennium. Gilead: Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau. Mayer:Janssen: Research Funding. Dilhuydy:Roche: Honoraria, Other: Travel reimbursement; Janssen: Honoraria, Other: Travel reimbursement; Mundipharma: Honoraria. Bartlett:Medimmune: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Genentech: Research Funding; ImaginAB: Research Funding; Astra Zeneca: Research Funding; Pharmacyclics: Research Funding; Janssen: Research Funding; Gilead: Consultancy; Seattle Genetics: Consultancy, Research Funding; Millenium: Research Funding; Celgene: Research Funding. Rule:Roche: Consultancy, Other: Travel reimbursement; Gilead: Research Funding; Celgene: Consultancy, Other: Travel reimbursement; J&J: Consultancy, Other: Travel reimbursement, Research Funding. Sun:Janssen/J&J: Employment, Equity Ownership. Phelps:Janssen/J&J: Employment, Equity Ownership. Mahler:Janssen: Employment, Other: Travel reimbursement. Salman:Janssen/J&J: Employment, Equity Ownership. Howes:Janssen/J&J: Employment, Equity Ownership. Hallek:AbbVie: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Roche: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Gilead: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Pharmacyclics: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Celgene: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Boehringher Ingelheim: Honoraria, Other: Speakers Bureau and/or Advisory Boards; Mundipharma: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Janssen: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding.

Abstract Introduction Recent results from the HELIOS phase 3 study in relapsed/refractory CLL/SLL demonstrated that the addition of ibrutinib to chemoimmunotherapy with bendamustine/rituximab (BR) leads to an 80% reduction in risk of progression or death compared with placebo + BR (Chanan-Khan et al. ASCO 2015). In addition to prolongation of progression-free survival (PFS; median not reached vs 13.3 months; hazard ratio: 0.203, 95% confidence interval: 0.150-0.276, p<0.0001), overall response rate (ORR) and rates of complete response (CR) or CR with incomplete marrow recovery (CRi) were significantly improved with ibrutinib + BR (ORR: 82.7% vs 67.8%; CR/CRi: 10.4% vs 2.8%). Here we report additional analyses on the quality of response with ibrutinib combined with BR. Methods In total, 578 patients (pts) with relapsed/refractory CLL/SLL requiring treatment were randomized 1:1 (289 per arm) to receive BR (≤ 6 cycles) with either ibrutinib (420 mg daily) or placebo. Purine analog refractoriness (yes vs no) and number of prior therapies (1 vs > 1) were stratification factors. Pts with deletion 17p (del17p; > 20% of cells) were excluded. All pts were required to have ≥ 1 abnormal lymph node (LN; defined as a measurable lesion > 1.5 cm). The primary end point was independent review committee (IRC)-assessed PFS. In this analysis, individual parameters of response (LN, spleen, overall radiology, absolute lymphocyte count [ALC], complete blood count [CBC], and bone marrow [BM]) were evaluated. Minimal residual disease (MRD) was assessed by flow cytometry using an 8-color panel (Rawstron AC, et al. Leukemia. 2007;21:956-964); MRD samples were collected at confirmation of suspected CR (bone marrow) and every 3 months thereafter (peripheral blood). Rate of MRD-negative response was defined as the proportion of pts who reached negative disease status (< 0.01%, ie, < 1 CLL cell/10,000 leukocytes) in any sample. Reported MRD rates are based on the intent-to-treat (ITT) population. Results The ORR assessed by the IRC was 82.7% with ibrutinib + BR vs 67.8% with placebo + BR (p < 0.0001), and was consistent with ORR reported by the treating physician (investigator assessed) (ORR: 86.2% vs 68.9%, p < 0.0001). However, rates of CR/CRi were higher by investigator assessment (21.4%, ibrutinib + BR vs 5.9%, placebo + BR) than IRC (10.4% vs 2.8%). The IRC employed an independent evaluation of radiological scans including stringent evaluation of LN and volumetric assessment of spleen size-the main reasons for the difference in CR/CRi rates between investigator and IRC assessment. At baseline, similar proportions of pts in each arm had bulky disease defined as LN > 5 cm (54%-58%) or abnormal spleen (~40%) as assessed by IRC. Complete resolution of previous CLL/SLL manifestations as assessed by the IRC was achieved more often in the ibrutinib + BR arm in comparison with placebo + BR for LN (34.6% vs 15.2%), spleen (56.7% vs 37.0%), overall radiology (21.1% vs 9.0%), and BM (19.7% vs 5.9%). Rates of normalization of ALC (> 90%) and CBC (> 70%) were high and similar in the 2 arms. MRD was assessed in 120 pts treated with ibrutinib + BR and 57 pts treated with placebo + BR and was negative in 37 pts and 14 pts, respectively, which corresponds with an MRD-negative response rate of 12.8% vs 4.8% for ibrutinib + BR vs placebo + BR (p = 0.0011). Investigator-determined responses by different levels of MRD are shown in Table 1. The percentage of pts with an MRD level < 1% was higher with ibrutinib + BR vs placebo + BR (32.2% vs 11.8%). Moreover, the percentage of pts with an MRD level < 0.1% was higher for ibrutinib + BR vs placebo + BR (24.6% vs 7.6%) suggesting that the depth of response with ibrutinib + BR was superior. Kaplan-Meier plots by MRD level (Figure 1) show that a lower MRD level was associated with a longer PFS. However, pts in the ibrutinib + BR arm had a more sustained response at every MRD level compared with pts in the placebo + BR arm. Conclusions Pts treated with ibrutinib + BR showed not only a higher ORR, but also a greater depth of response, with more CRs and a higher rate of resolution of LN, spleen, and BM involvement. Furthermore, the rate and depth of MRD negativity was improved, and appeared to last longer in pts treated with ibrutinib + BR compared with pts receiving placebo + BR. With a median follow up of 17 months in the ibrutinib + BR arm, no MRD-negative pts and few MRD-positive pts had progressed, thus evaluating a trend in PFS with MRD negativity is currently limited in this arm. Disclosures Cramer: Gilead: Other: Travel grant, Research Funding; Glaxo Smith Klein/Novartis: Research Funding; Astellas: Other: Travel grant; Mundipharma: Other: Travel grant; Janssen: Other: Travel grant, Research Funding, Speakers Bureau; Hoffman LaRoche: Other: Travel grant, Research Funding, Speakers Bureau. Off Label Use: Combination of bendamustine, obinutuzumab and ibrutinib for treatment of CLL. Fraser:Hoffman LaRoche: Consultancy, Honoraria; Janssen: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding. Demirkan:Amgen: Consultancy; Celgene: Other: Travel reimbursement. Santucci Silva:Merck: Research Funding; Celgene: Research Funding; GSK: Research Funding; Janssen: Other: Travel reimbursement, Research Funding; Hoffman LaRoche: Other: Travel reimbursement, Research Funding; Novartis: Other: Travel reimbursement. Janssens:Mundipharma: Speakers Bureau; Roche: Consultancy, Speakers Bureau; Janssen: Consultancy. Goy:Allos, Biogen Idec, Celgene, Genentech, and Millennium. Gilead: Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau. Mayer:Janssen: Research Funding. Dilhuydy:Roche: Honoraria, Other: Travel reimbursement; Janssen: Honoraria, Other: Travel reimbursement; Mundipharma: Honoraria. Bartlett:Millenium: Research Funding; Medimmune: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Genentech: Research Funding; ImaginAB: Research Funding; Astra Zeneca: Research Funding; Pharmacyclics: Research Funding; Janssen: Research Funding; Gilead: Consultancy; Seattle Genetics: Consultancy, Research Funding; Celgene: Research Funding. Rule:Roche: Consultancy, Other: Travel reimbursement; J&J: Consultancy, Other: Travel reimbursement, Research Funding; Celgene: Consultancy, Other: Travel reimbursement; Gilead: Research Funding. Sun:Janssen/J&J: Employment, Equity Ownership. Phelps:Janssen/J&J: Employment, Equity Ownership. Mahler:Janssen: Employment, Other: Travel reimbursement. Salman:Janssen/J&J: Employment, Equity Ownership. Schaffer:Janssen: Employment. Balasubramanian:Pharmacyclics LLC, an AbbVie Company: Equity Ownership; Janssen: Employment, Equity Ownership. Howes:Janssen/J&J: Employment, Equity Ownership. Hallek:AbbVie: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Celgene: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Pharmacyclics: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Gilead: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Boehringher Ingelheim: Honoraria, Other: Speakers Bureau and/or Advisory Boards; Roche: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Mundipharma: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Janssen: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding.

Abstract Background: The majority of pts with MF present with a mutation in exon 14 of the JAK2 gene (JAK2V617F). Studies have suggested that in pts with MF and this mutation, a lower AB is associated with a myelodepletive phenotype and shortened survival (Tefferi, Leukemia 2008; Guglielmelli Blood 2009; reviewed in Vannucchi, Ther Adv Hematol 2011). For example, in a Cox proportional hazard model for factors predictive of overall survival (OS) in pts with primary MF, a JAK2V617F AB of <25% was associated with a shortened OS (p=0.002; Guglielmelli, Blood 2009). In the phase III trials of ruxolitinib (RUX) therapy in JAK inhibitor-naïve MF, RUX-treated pts had a median decrease in AB of 16% (maximal) in COMFORT-I followed up to 216 weeks and 7% in COMFORT-II at 48 weeks. The median AB at the start of therapy was not reported for COMFORT-I and in COMFORT-II was 84.5% (Cervantes, Blood 2013; Deininger, Blood2015). Methods: In this communication, we report on clinical correlates of quantitative baseline JAK2 mutational status and the effect of treatment on JAK2V617Fmutational burden in the PERSIST-1 trial. This trial enrolled JAK inhibitor-naïve pts with primary or secondary MF without restrictions on baseline platelet counts, randomized 2:1 between PAC and BAT (excluding JAK2 inhibitors) arms. Stratifications included Dynamic International Prognostic Scoring System (DIPSS) risk category, and baseline platelet counts (<50,000/μL, 50,000-100,000/μL, >100,000/μL). Following the 24-week primary analysis, crossover was allowed by physician/pt choice and 90/107 BAT-treated pts (84%) crossed over to receive PAC. Baseline characteristics have been previously reported (Mesa, ASCO 2016) and included 203/327 (62%) pts with Primary MF, 42 (13%) with post-essential thrombocythemia MF and 81 (25%) with post-polycythemia vera MF. 320 of 327 pts had informative PCR testing for JAK2V617F. We report the baseline characteristics of pts with high (≥50%) AB of JAK2V617F, low (<50%) AB of JAK2V617Fand those without a detectable mutation at baseline (<0.1%), as well as the effect of PAC and BAT on AB and correlation with outcome measures. Results: 131 (40.9%) had AB >50% (high AB), 115 (35.9%) had an AB ≥0.1% and ≤50% (low AB), and 74 (23.1%) had AB <0.1% (wild-type JAK2). Median AB values were 80.3% for the high AB group and 30.3% for the low AB group. Baseline characteristics that were significantly different between high and low AB pts are shown in the Table. No differences were noted in the DIPSS risk category or baseline percentage of blasts between pts with low or high AB. There were a higher percentage of pts with a lower AB in the PAC arm (64% vs. 48%; p=0.01). PAC therapy resulted in a median decrement in AB at Week 24 of −15.8% vs −7.9% for pts in the BAT arm (Figure). The median greatest reduction from baseline in AB in PAC-treated pts was −31.6%. Decrease in AB was strongly correlated with spleen volume reduction (p=0.003) and trended towards correlation with improvement in total symptom score (p=0.07) in PAC-treated, but not in BAT-treated pts. Overall survival was shorter in PAC-treated pts with a minimal AB reduction vs pts with greater decreases in AB. Conclusions: In the PERSIST-1 trial, pts with a JAK2V617FAB of <50% had substantially different disease and demographic characteristics when compared with those pts with a >50% AB despite similar distribution of DIPSS scores. In this trial, reduction in AB associated with PAC, but not BAT correlated with clinical benefit. Disclosures Vannucchi: Novartis: Consultancy, Research Funding, Speakers Bureau; Baxalta: Speakers Bureau; Shire: Speakers Bureau. Mead:Baxalta: Consultancy, Honoraria. Perkins:Novartis Oncology: Consultancy, Honoraria; Bristol-Myers Squibb: Other: Travel, Accommodations, Expenses. Mayer:CTI BioPharma Corp.: Other: Travel, Accommodations, Expenses, Research Funding. Schouten:Sanofi: Consultancy; Novartis: Consultancy. Farber:Alexion: Equity Ownership; Celgene: Honoraria, Research Funding, Speakers Bureau; Genentech: Research Funding, Speakers Bureau; Acerta: Research Funding; Gilead: Research Funding, Speakers Bureau; TG Therapeutics: Research Funding; Seattle Genetics: Speakers Bureau; Pharmacyclics: Speakers Bureau. Kiladjian:Novartis: Honoraria, Research Funding; AOP Orphan: Consultancy, Research Funding. Nangalia:Novartis: Consultancy, Other: Travel, Accommodations, Expenses. Dean:CTI BioPharma Corp.: Employment, Equity Ownership. Zhou:CTI BioPharma Corp.: Employment, Equity Ownership. Singer:CTI BioPharma Corp.: Employment, Equity Ownership, Other: Leadership . Mesa:Novartis: Consultancy, Honoraria; Incyte: Research Funding; Gilead: Research Funding; CTI BioPharma: Research Funding; Celgene: Research Funding; Genetech: Research Funding; Promedior: Research Funding. Harrison:Novartis: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; CTI BioPharma: Consultancy, Honoraria, Speakers Bureau; Baxter: Consultancy, Honoraria; Shire: Speakers Bureau; Gilead: Speakers Bureau; Incyte: Speakers Bureau.

Abstract Purpose: Previous studies have suggested that higher circulating 25-hydroxyvitamin D [25(OH)D] levels are associated with decreased colorectal cancer risk and improved survival. However, the influence of vitamin D status on disease progression and patient survival remains largely unknown for patients with advanced or metastatic colorectal cancer. Experimental Design: We prospectively collected blood samples in 1,041 patients with previously untreated advanced or metastatic colorectal cancer participating in a randomized phase III clinical trial of first-line chemotherapy plus biologic therapy. We examined the association of baseline plasma 25(OH)D levels with overall survival (OS) and progression-free survival (PFS). Cox proportional hazards models were used to calculate hazard ratios (HRs) and confidence intervals (CIs), adjusted for prognostic factors and confounders. Results: At study entry, 63% of patients were vitamin D deficient (&lt;20 ng/mL) and 31% were vitamin D insufficient (20–&lt;30 ng/mL). Higher 25(OH)D levels were associated with an improvement in OS and PFS (Ptrend = 0.0009 and 0.03, respectively). Compared with patients in the bottom quintile of 25(OH)D (≤10.8 ng/mL), those in the top quintile (≥24.1 ng/mL) had a multivariable-adjusted HR of 0.66 (95% CI, 0.53–0.83) for OS and 0.81 (95% CI, 0.66–1.00) for PFS. The improved survival associated with higher 25(OH)D levels was consistent across patient subgroups of prognostic patient and tumor characteristics. Conclusions: In this large cohort of patients with advanced or metastatic colorectal cancer, higher plasma 25(OH)D levels were associated with improved OS and PFS. Clinical trials assessing the benefit of vitamin D supplementation in patients with colorectal cancer are warranted.