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Abstract Background The incidence of young-onset colorectal cancer (yoCRC) is increasing. It is unknown if there are survival differences between young and older patients with metastatic colorectal cancer (mCRC). Methods We studied the association of age with survival in 2326 mCRC patients enrolled in the Cancer and Leukemia Group B and SWOG 80405 trial, a multicenter, randomized trial of first-line chemotherapy plus biologics. The primary and secondary outcomes of this study were overall survival (OS) and progression-free survival (PFS), respectively, which were assessed by Kaplan-Meier method and compared among younger vs older patients with the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated based on Cox proportional hazards modeling, adjusting for known prognostic variables. All statistical tests were 2-sided. Results Of 2326 eligible subjects, 514 (22.1%) were younger than age 50 years at study entry (yoCRC cohort). The median age of yoCRC patients was 44.3 vs 62.5 years in patients aged 50 years and older. There was no statistically significant difference in OS between yoCRC vs older-onset patients (median = 27.07 vs 26.12 months; adjusted HR = 0.98, 95% CI = 0.88 to 1.10; P = .78). The median PFS was also similar in yoCRC vs older patients (10.87 vs 10.55 months) with an adjusted hazard ratio of 1.02 (95% CI = 0.92 to 1.13; P = .67). Patients younger than age 35 years had the shortest OS with median OS of 21.95 vs 26.12 months in older-onset patients with an adjusted hazard ratio of 1.08 (95% CI = 0.81 to 1.44; Ptrend = .93). Conclusion In this large study of mCRC patients, there were no statistically significant differences in survival between patients with yoCRC and CRC patients aged 50 years and older.

12102 Background: Allostatic load (AL) conceptualizes the effects of chronic psychosocial adversity on physiologic dysregulation. To date, studies have shown an association between elevated AL and higher disease-specific and overall mortality among cancer patients; however, none have focused on multiple myeloma (MM) patients. We aim to understand the relationship between baseline AL, symptom burden, and mortality among patients enrolled in the E1A11 therapeutic trial in MM. Methods: ECOG-ACRIN E1A11 was a phase III RCT comparing induction with Bortezomib (Arm A) versus Carfilzomib (Arm B) in conjunction with Lenalidomide +Dexamethasone. AL included 7 biomarkers: BMI, alkaline phosphatase, creatinine, C-reactive protein, white blood cell count, albumin and creatinine clearance. AL7 was a composite summary score with a point was assigned for each biomarker value in the highest quartile, except for albumin and creatinine clearance, where a point was assigned for values in the lowest quartile. Endpoints included symptom burden at baseline and ̃1 month, non-completion of induction therapy, and overall survival (OS). Functional Assessment of Cancer Therapy Multiple Myeloma (FACT-MM) items assessed patient-reported symptom burden, including fatigue (item HI7), pain (GP4), and bother by side effects of treatment (GP5) on a 5-point Likert scale. Multivariable logistic regressions assessed the effect of AL7 (ranging 0-7) on high-pain, -fatigue, and -bother (QOL score > = 3 vs < 3), and non-completion of induction therapy. The effect of AL7 on OS was assessed using multivariable Cox regression. Regression covariates included study arm, age, sex, race, ECOG performance status, and the target symptom burden score at baseline. Results: The study cohort included 1087 patients. Mean baseline AL7 was 1.8 (±1.4). In adjusted analysis, a unit increase in AL7 was associated with a greater odds of high pain (OR 1.15, 95%CI [1.04-1.27]) and high fatigue (OR 1.19, 95%CI [1.07-1.32]) at baseline, which did not persist at ̃1 month (pain OR 0.96, 95%CI [0.84-1.10]; fatigue OR 1.03, 95%CI [0.91-1.16]). There was no association between AL7 and high side effect bother at baseline (OR 1.06, 95% CI [0.83-1.35]) or at ̃1 month (OR 1.06, 95%CI [0.90-1.24]). There was no association between AL7 and induction non-completion (OR 1.07, 95%CI [0.96-1.18]). Notably, each unit increase in AL7 was associated with higher mortality (HR 1.26, 95%CI [1.14-1.39]). Conclusions: Despite its association with fatigue and pain at baseline, AL7 was not associated with these symptoms at ̃1 month nor induction non-completion. However, elevated baseline AL7 was associated with poorer OS. AL composite score at baseline, which we interpret as a measure of physiological dysregulation associated with adverse social factors, may have implications on clinical outcomes within clinical trials despite presumed equal treatment access.

3588 Background: Growing data suggest dietary factors are associated with survival among pts with non-metastatic CRC. However, data on diet and survival among pts with advanced or metastatic disease are very limited. Methods: We prospectively examined dietary fat intake assessed at initiation of treatment for advanced or metastatic CRC in relation to OS and PFS. This analysis was conducted among 1,149 pts in the CALGB 80405 randomized controlled trial who completed a validated food frequency questionnaire. We examined intakes of saturated, monounsaturated, and polyunsaturated (total n-3, long-chain n-3, and total n-6) fats as well as animal and vegetable fats. Based on data from non-metastatic CRC and other cancers, we hypothesized that higher intakes of long-chain n-3 fatty acids and vegetable fats would be associated with longer OS and PFS and higher intakes of saturated fat and animal fat would be associated with shorter OS and PFS. We used Cox proportional hazards regression to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI). Results: Over a median follow-up of 6.1 years [y; interquartile range (IQR): 5.3, 7.2 y], we observed 974 deaths and 103 events of progression without death during follow-up. Participants in this analysis had a median age of 59 y (IQR: 51 to 67 y); 41% were female and 86% identified as white. We observed no statistically significant associations between any type of dietary fat and OS. However, vegetable fat was non-linearly associated with longer PFS (HR comparing 4th to 1st quartile: 0.78; 95% CI: 0.64, 0.96; p-trend: 0.10). We also observed a linear association between continuous saturated fat and PFS (HR per 5% kcal/d: 1.21; 95% CI: 1.03, 1.42; p-value: 0.02), perhaps driven by pts with high saturated fat intake. Conclusions: We observed no statistically significant associations between types of dietary fat and OS among pts with advanced or metastatic CRC. However, a healthy diet that includes vegetable fat and is modest in saturated fat may be associated with longer PFS. Future studies to replicate these findings and examine diet in relation to cancer survival in racially/ethnically diverse populations are needed. Support: K07CA197077, U10CA180821, U10CA180882, https://acknowledgments.alliancefound.org . Clinical trial information: NCT00265850.

3575 Background: Pts with mCRC frequently receive ≥1 sequential treatment TL. Approximately 50%-60% of pts receive second-line (L2) and 20%-30% third-line (L3) regimens in routine practice. We investigated the pts clinical/tumor characteristics and their prognostic impact across TL. Methods: Data from 37,560 pts enrolled in 48 randomized trials (34 in first (L1), 9 in L2, and 5 in L3) were analyzed. Candidate variables (VAR) measured at enrollment were sex, age, body mass index, performance status (PS), bilirubin, hemoglobin (Hb), platelets (Pl), derived white blood cells-to-absolute neutrophil counts ratio (WBC/ANC), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), primary tumor location, and number and location of metastatic sites (MS). Missing data were imputed. VAR with significant value at all TL were selected to construct a prognostic score of overall survival (OS) in training set (TS, n=30,050; 80%). For each TL, the score was calculated as the sum on the estimations of the VAR’ coefficients from the common multivariate model; Cox’s model was used to define risk groups. The discrimination capability was assessed using the Harrell’s C-index. External validation was done in the validation set (VS, n=7,510; 20%). Results: A total of 26,974 pts in L1, 7,693 pts in L2 and 2,893 pts in L3 were analyzed. The following characteristics increased continuously over TL: ≥2 MS (57%, 72%, 82%), lung metastases (50%, 74%, 91%), lymph nodes metastases (51%, 61%, 80%), KRAS mutation (37%, 47%, 51%) and elevated ALP (46%, 52%, 61%). BRAF mutation decreased (9%, 7%, 5%). In L1 vs L3 trials, 70% vs 89% of patients had primary tumor resection, 10% vs 80% had at least one metastasectomy and 31% vs 78% had a late metachronous (>12 months) metastasis. 7 independent VAR were retained in the prognostic score (PS, Hb, Pl, WBC/ANC, LDH, ALP, and the number of MS); four pt groups with significantly different prognoses were defined (table). This score remained valid when excluding pts with PS 2. Third-line oral drugs (vs placebo) and subsequent line (L2/L1 or L3/L2) were effective in all prognostic groups. Conclusions: Clinical/tumor pt characteristics significantly varied over subsequent TL in patients included in randomized trials. The same prognostic model using practical clinical and biological variables can be used in all TL.[Table: see text]

3568 Background: Diets inducing an elevated insulin response have been associated with increased recurrence and mortality in patients with non-metastatic colorectal cancer, but it remains unknown if postprandial hyperinsulinemia also affects progression and mortality in mCRC patients. The goal of this study was to assess the influence of dietary insulin load (DIL) and dietary insulin index (DII) on survival of mCRC patients. Methods: This was a prospective cohort study of 1,177 patients with previously untreated mCRC enrolled in a phase III trial of systemic chemotherapy plus biologics who reported dietary intake within one month after chemotherapy initiation. DIL was calculated as a function of food insulin index and the energy content of individual foods reported on a food frequency questionnaire. DII was calculated by dividing DIL by total energy intake. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS) and treatment-related adverse events (TRAEs). The primary statistical test was a test for trend, which was performed using the median value for each quintile of dietary insulin score as a continuous variable. Cox proportional hazards regression was used to adjust for potential confounders including assigned treatment arm, known prognostic factors, comorbidities, body mass index, and physical activity. Results: Higher DIL was significantly associated with worse OS (ptrend = 0.04); patients in the highest quintile survived 34.1 months, compared to 27.7 months in the lowest quintile (Cox hazard ratio [HR] 1.22, 95% confidence interval [CI] 0.99 - 1.51). Higher DII was non-significantly associated with worse OS (HR 1.18, 95% CI 0.94 - 1.48, ptrend = 0.09). There was no significant association between dietary insulin scores and PFS. The influence of dietary insulin scores on survival did not differ significantly by various molecular markers involved in the insulin signaling pathway, including C-peptide, adiponectin, IGF-1, IGFBP-3, and IGFBP-7. Higher dietary insulin scores were significantly associated with greater risk of any TRAE. Those with a DIL greater than the median had a 75.4% rate of any TRAE, compared to 70.8% in those with a DIL less than or equal to the median (HR 1.19, 95% CI 1.03 - 1.38, p=0.02); the most significant associations were with neutropenia (HR 1.30, 95% CI 1.05 - 1.61, p=0.01) and diarrhea (HR 1.43, 95% CI 1.00 - 2.06, p=0.05). Conclusions: Higher DIL was significantly associated with worse OS, and both higher DIL and DII were significantly associated with increased TRAEs, in patients with previously untreated mCRC. These findings may inform future dietary recommendations for patients with mCRC. Further investigation into the molecular mechanisms underlying these associations is warranted. Clinical trial information: NCT00265850.

Abstract Background Disparities in colon cancer outcomes have been reported across race and socioeconomic status, which may reflect, in part, access to care. We sought to assess the influences of race and median household income (MHI) on outcomes among colon cancer patients with similar access to care. Methods We conducted a prospective, observational study of 1206 stage III colon cancer patients enrolled in the CALGB 89803 randomized adjuvant chemotherapy trial. Race was self-reported by 1116 White and 90 Black patients at study enrollment; MHI was determined by matching 973 patients’ home zip codes with publicly available US Census 2000 data. Multivariate analyses were adjusted for baseline sociodemographic, clinical, dietary, and lifestyle factors. All statistical tests were 2-sided. Results Over a median follow-up of 7.7 years, the adjusted hazard ratios for Blacks (compared with Whites) were 0.94 (95% confidence interval [CI] = 0.66 to 1.35, P = .75) for disease-free survival, 0.91 (95% CI = 0.62 to 1.35, P = .65) for recurrence-free survival, and 1.07 (95% CI = 0.73 to 1.57, P = .73) for overall survival. Relative to patients in the highest MHI quartile, the adjusted hazard ratios for patients in the lowest quartile were 0.90 (95% CI = 0.67 to 1.19, Ptrend = .18) for disease-free survival, 0.89 (95% CI = 0.66 to 1.22, Ptrend = .14) for recurrence-free survival, and 0.87 (95% CI = 0.63 to 1.19, Ptrend = .23) for overall survival. Conclusions In this study of patients with similar health-care access, no statistically significant differences in outcomes were found by race or MHI. The substantial gaps in outcomes previously observed by race and MHI may not be rooted in differences in tumor biology but rather in access to quality care.

Abstract Background: Financial burden during cancer treatment is associated with compromised patient-reported outcomes (PROs). Being aware of impending costs may help preserve affected PROs during treatment, as patients can adjust their financial expectations. We aimed to determine if the relationship between financial burden and PROs differs among those who were aware versus unaware of transplant-related costs before hematopoietic cell transplantation (HCT) for hematologic malignancy. Methods: In 2015, we administered a mailed survey to adult patients at least 150 days after autologous or allogeneic HCT at three centers: Dana-Farber Cancer Institute, Roswell Park Cancer Institute, and Mayo Clinic Arizona. We assessed pre-treatment awareness of transplant-related costs, decreased household income after HCT, and financial hardship (defined as any one or two of the following: reporting being either unsatisfied with present finances, having difficulty meeting monthly bill payments, or not having enough money at the end of the month; given that experiencing all three would represent extreme hardship likely to impact PROs regardless of awareness, we excluded this group). A seven-point scale was provided for perceptions of overall quality of life (QOL, and patient-reported stress was measured with the Perceived Stress Scale (PSS-4). We fit regression models-stratified by awareness-to assess for the association of income decline and financial hardship with QOL below the median and perceived stress above the median (adjusting for transplant type, sex, age, race, marital status, income, distance to transplant center, and time since diagnosis). Results:In the overall survey cohort (n=325; response rate = 65.1%), 21.6% reported being unaware of HCT-related costs, with no differences due to age, race, income, or education as compared to those who were aware. Patients who reported being aware prior to transplant most often reported being informed of costs by a social worker (40.6%) and least often by a physician (23.4%; sources not mutually exclusive). Among aware patients, income decline after HCT was not associated with QOL below the median (AOR 1.4 [0.8, 2.5]; p=0.24); in contrast, among the unaware, income decline increased the odds of reporting worse QOL (AOR 4.3 [1.1, 16.7]; p=0.04). Among the aware, self-reported financial hardship was associated with worse QOL after HCT (AOR 2.7 [1.5, 4.8]; p=&lt;.001), but the odds were even higher among the unaware (AOR 4.7 [1.2, 19.4]; p=0.03). Similar increases were observed among the unaware for the association of decline in income and financial hardship with increased perceived stress. Conclusions: In this large multi-institutional cohort of patients post-HCT, more than one-fifth reported being unaware of transplant-related costs before the procedure. Moreover, this analysis suggests that pre-treatment awareness of transplant-related costs may ameliorate the impact of post-HCT financial burden on patient-reported outcomes. Figure Figure. Disclosures Khera: Novartis: Consultancy. Zafar: Novartis: Other: Spouse's Employment.

PURPOSEMutations in the HRAS (m HRAS) proto-oncogene occur in 4%-8% of patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Tipifarnib is a farnesyltransferase inhibitor that disrupts HRAS function. We evaluated the efficacy of tipifarnib in patients with R/M m HRAS HNSCC.METHODSWe enrolled 30 patients with R/M HNSCC in a single-arm, open-label phase II trial of tipifarnib for m HRAS malignancies; one additional patient was treated on an expanded access program. After an ad hoc analysis of the first 16 patients with HNSCC with m HRAS variant allele frequency (VAF) data, enrollment was limited to those with a m HRAS VAF of ≥ 20% (high VAF). The primary end point was objective response rate. Secondary end points included assessing safety and tolerability. Patients received tipifarnib 600 or 900 mg orally twice daily on days 1-7 and 15-21 of 28-day cycles.RESULTSOf the 22 patients with HNSCC with high VAF, 20 were evaluable for response at the time of data cutoff. Objective response rate for evaluable patients with high-VAF HNSCC was 55% (95% CI, 31.5 to 76.9). Median progression-free survival on tipifarnib was 5.6 months (95% CI, 3.6 to 16.4) versus 3.6 months (95% CI, 1.3 to 5.2) on last prior therapy. Median overall survival was 15.4 months (95% CI, 7.0 to 29.7). The most frequent treatment-emergent adverse events among the 30 patients with HNSCC were anemia (37%) and lymphopenia (13%).CONCLUSIONTipifarnib demonstrated encouraging efficacy in patients with R/M HNSCC with HRAS mutations for whom limited therapeutic options exist ( NCT02383927 ).

Abstract Autologous stem cell transplantation (ASCT) can be curative for patients with relapsed/refractory Hodgkin lymphoma (HL). Based on studies suggesting that anti-PD-1 monoclonal antibodies (mAbs) can sensitize patients to subsequent chemotherapy, we hypothesized that anti-PD-1 therapy before ASCT would result in acceptable outcomes among high-risk patients who progressed on or responded insufficiently to ≥1 salvage regimen, including chemorefractory patients who are traditionally considered poor ASCT candidates. We retrospectively identified 78 HL patients who underwent ASCT after receiving an anti-PD-1 mAb (alone or in combination) as third-line or later therapy across 22 centers. Chemorefractory disease was common, including 42 patients (54%) refractory to ≥2 consecutive systemic therapies immediately before anti-PD-1 treatment. Fifty-eight (74%) patients underwent ASCT after anti-PD-1 treatment, while 20 patients (26%) received additional therapy after PD-1 blockade and before ASCT. Patients received a median of 4 systemic therapies (range, 3-7) before ASCT, and 31 patients (41%) had a positive pre-ASCT positron emission tomography (PET) result. After a median post-ASCT follow-up of 19.6 months, the 18-month progression-free survival (PFS) and overall survival were 81% (95% CI, 69-89) and 96% (95% confidence interval [CI], 87-99), respectively. Favorable outcomes were observed for patients who were refractory to 2 consecutive therapies immediately before PD-1 blockade (18-month PFS, 78%), had a positive pre-ASCT PET (18-month PFS, 75%), or received ≥4 systemic therapies before ASCT (18-month PFS, 73%), while PD-1 nonresponders had inferior outcomes (18-month PFS, 51%). In this high-risk cohort, ASCT after anti-PD-1 therapy was associated with excellent outcomes, even among heavily pretreated, previously chemorefractory patients.