Citations

3539 Background: Previous studies suggest a possible gender-specific response to Bev in mCRC, showing a benefit in males, while the effect in females is less significant. Therefore, we evaluated response to Bev according to gender. Methods: Data from 3369 mCRC patients enrolled on 4 first-line randomized trials testing Bev (2000-2007) were pooled. Association between gender and progression-free survival (PFS)/overall survival (OS) was evaluated by stratified Cox regression model, adjusted for potential confounders. Predictive value was evaluated by interaction (inter.) effect between gender and treatment. In a pre-planned secondary analysis, analyses were stratified using an age cut-point of 60 years (commonly used in breast cancer trials) to evaluate the possible role of menopausal-related effects. Results: OS was not statistically different between males and females (median OS [mOS], 18.8 vs. 17.6 months [mo], adjusted hazard ratio [HRadj], 0.93, 95% confidence interval [CI], 0.84-1.03, p, 0.15) in the overall population. Bev was associated with an improved mOS in males and females, with a 2.3 and 0.6 mo benefit, respectively, as well as an improved PFS. There was no statistically significant interaction effect between gender and treatment (see table). Further stratified by age (< vs. ≥ 60 years), Bev resulted in improved PFS and OS in both genders, at all ages, except for the effect in young females which did not reach statistical significance (see table). Conclusions: Our results confirmed the mOS benefit from addition of Bev to first-line chemotherapy in mCRC in both genders, although the benefit in females was < 1 month. For females under the age of 60, there are uncertainties for mOS benefit from addition of Bev and further evaluation is needed. [Table: see text]

3035 Background: Energy balance-associated biomarkers such as insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) have been associated with risk and prognosis of various malignancies. Their relationship to disease progression and mortality in metastatic colorectal cancer (mCRC) requires further study. Methods: In a prospective cohort study, baseline plasma IGFBP-3, IGFBP-7, C-peptide, IGF-I, and adiponectin were measured at trial registration among 1,086 patients participating in a National Cancer Institute-sponsored clinical trial of first-line therapy for mCRC. We used Cox proportional hazards regression to adjust for confounders and examine associations of biomarkers with overall (OS) and progression-free survival (PFS). Results: Higher plasma IGFBP-3 was associated with longer OS (adjusted Ptrend < .001) and PFS (adjusted Ptrend = .003). Compared to patients in the lowest IGFBP-3 quintile, patients in the highest quintile experienced an adjusted HR for all-cause mortality of 0.58 (95% CI 0.42 to 0.78) and for disease progression or mortality of 0.60 (95% CI 0.45 to 0.82). Higher plasma IGFBP-7 was associated with shorter OS (adjusted Ptrend < .001) and PFS (adjusted Ptrend = .02). Compared to patients in the lowest IGFBP-7 quintile, patients in the highest quintile experienced an adjusted HR for all-cause mortality of 1.52 (95% CI 1.24 to 1.88) and for disease progression or mortality of 1.28 (95% CI 1.05 to 1.57). C-peptide and IGF-I were not significantly associated with patient outcomes (adjusted Ptrend = .73 and .30 for OS). Adiponectin was not associated with OS; there was a U shaped association between adiponectin and PFS, wherein low and high values were associated with shorter PFS ( Pnon-linear trend = .03). Conclusions: In patients with mCRC, high plasma IGFBP-3 and low IGFBP-7 were associated with reduced risk of disease progression and mortality. These data suggest that energy-balance associated biomarkers may offer prognostic and biologic insights into mCRC. Support: U10CA180821, U10CA180882, BMS, Genentech, Pfizer, Sanofi; https://acknowledgments.alliancefound.org .

Abstract Background Little is known about how complementary and alternative medicine (CAM) is discussed in cancer care across varied settings in the U.S. Methods In two practices affiliated with one academic medical center in southern California (SoCal), and one in the upper Midwest (UM), we audio-recorded patient-clinician interactions in medical oncology outpatient practices. We counted the frequency and duration of CAM-related conversations. We coded recordings using the Roter Interaction Analysis System. We used chi-square tests for bivariate analysis of categorical variables and generalized linear models for continuous variables to examine associations between dialogue characteristics, practice setting, and population characteristics with the occurrence of CAM discussion in each setting followed by multivariate models adjusting for clinician clustering. Results Sixty-one clinicians and 529 patients participated. Sixty-two of 529 (12%) interactions included CAM discussions, with significantly more observed in the SoCal university practice than in the other settings. Visits that included CAM were on average 6 minutes longer, with CAM content lasting an average of 78 seconds. In bivariate tests of association, conversations containing CAM included more psychosocial statements from both clinicians and patients, higher patient-centeredness, more positive patient and clinician affect, and greater patient engagement. In a multivariable model including significant bivariate terms, conversations containing CAM were independently associated with higher patient-centeredness, slightly longer visits, and being at the SoCal university site. Conclusion The frequency of CAM-related discussion in oncology varied substantially across sites. Visits that included CAM discussion were longer and more patient centered. Implications for Practice The Institute of Medicine and the American Society of Clinical Oncology have called for more open discussions of complementary and alternative medicine (CAM). But little is known about the role population characteristics and care contexts may play in the frequency and nature of those discussions. The present data characterizing actual conversations in practice complements a much larger literature based on patient and clinician self-report about CAM disclosure and use. It was found that CAM discussions in academic oncology visits varied significantly by practice context, that the majority were initiated by the patient, and that they may occur more when visit time exists for lifestyle, self-care, and psychosocial concerns.

PURPOSETo determine the predictive and prognostic value of the consensus molecular subtypes (CMSs) of colorectal cancer (CRC) that represent a merging of gene expression–based features largely in primary tumors from six independent classification systems and provide a framework for capturing the intrinsic heterogeneity of CRC in patients enrolled in CALGB/SWOG 80405.PATIENTS AND METHODSCALGB/SWOG 80405 is a phase III trial that compared the addition of bevacizumab or cetuximab to infusional fluorouracil, leucovorin, and oxaliplatin or fluorouracil, leucovorin, and irinotecan as first-line treatment of advanced CRC. We characterized the CMS classification using a novel NanoString gene expression panel on primary CRCs from 581 patients enrolled in this study to assess the prognostic and predictive value of CMSs in these patients.RESULTSThe CMSs are highly prognostic for overall survival (OS; P < .001) and progression-free survival (PFS; P < .001). Furthermore, CMSs were predictive for both OS ( P for interaction < .001) and PFS ( P for interaction = .0032). In the CMS1 cohort, patients treated with bevacizumab had a significantly longer OS than those treated with cetuximab ( P < .001). In the CMS2 cohort, patients treated with cetuximab had a significantly longer OS than patients treated with bevacizumab ( P = .0046).CONCLUSIONThese findings highlight the possible clinical utility of CMSs and suggests that refinement of the CMS classification may provide a path toward identifying patients with metastatic CRC who are most likely to benefit from specific targeted therapy as part of the initial treatment.

PURPOSE CALGB/SWOG 80405 was a randomized phase III trial that found no statistically significant difference in overall survival (OS) in patients with first-line metastatic colorectal cancer treated with chemotherapy plus either bevacizumab or cetuximab. Primary tumor DNA from 843 patients has been used to discover genetic markers of OS. PATIENTS AND METHODS Gene mutations were determined by polymerase chain reaction. Microsatellite status was determined by genotyping of microsatellites. Tumor mutational burden (TMB) was determined by next-generation sequencing. Cox proportional hazard models were used, with adjusting factors. Interaction of molecular alterations with either the bevacizumab or the cetuximab arms was tested. RESULTS Patients with high TMB in their tumors had longer OS than did patients with low TMB (hazard ratio [HR], 0.73 [95% CI, 0.57 to 0.95]; P = .02). In patients with microsatellite instability–high (MSI-H) tumors, longer OS was observed in the bevacizumab arm than in the cetuximab arm (HR, 0.13 [95% CI, 0.06 to 0.30]; interaction P < .001 for interaction between microsatellite status and the two arms). Patients with BRAF mutant tumors had shorter OS than did patients with wild-type (WT) tumors (HR, 2.01 [95% CI, 1.49 to 2.71]; P < .001). Patients with extended RAS mutant tumors had shorter OS than did patients with WT tumors (HR, 1.52 [95% CI, 1.26 to 1.84]; P < .001). Patients with triple-negative tumors (WT for NRAS/ KRAS/ BRAF) had a median OS of 35.9 months (95% CI, 33.0 to 38.8 months) versus 22.2 months (95% CI, 19.6 to 24.4 months ) in patients with at least one mutated gene in their tumors ( P < .001). CONCLUSION In patients with metastatic colorectal cancer treated in first line, low TMB, and BRAF and RAS mutations are negative prognostic factors. Patients with MSI-H tumors benefited more from bevacizumab than from cetuximab, and studies to confirm this effect of MSI-H are warranted.