Citations

8034 Background: Multiple myeloma (MM), a monoclonal plasma cell disorder, is one of the most common hematologic malignancies in the US. In preclinical studies, metformin demonstrated plasma cells cytotoxicity. However, there is lack of studies translating the effect of metformin into the clinical setting. Therefore, we assessed the clinical effect of metformin in patients (pts) with MM. Methods: All MM pts who underwent stem cell transplant (SCT) at the Mayo Clinic Rochester from 2007 to 2012 were reviewed. Patients were grouped based on metformin use. Initial diagnosis at our institution and ≥12 months of follow up were required. Kaplan-Meier method and Cox regression were used for time-to-event and multivariate analysis. Results: Out of 687 pts, 78 (11.4%) were using metformin at the time of MM diagnosis. Baseline characteristics in the metformin (Mt) and no-metformin (NMt) groups were similar (Table). Median (M) metformin dose was 2000 mg daily and m duration of metformin use from MM diagnosis was 22 months. Pts on the Mt group achieved higher rates of CR after SCT (41% vs. 29%, p<0.02). Median PFS after SCT was longer in the Mt group, 31.3 months (95% CI: 10.4-52.2) vs. 16.6 months in the NMt group (95%CI: 14.5-18.7) p<0.04. There was a trend towards longer OS in the Mt group, but it was not statistically significant (170 vs. 106 months, p<0.10). In a multivariate analysis of metformin use, age, ISS, LDH, and cytogenetics/FISH, the former was an independent predictor of PFS after SCT (OR: 0.38, 95%CI: 0.20-0.68, p<0.001). Conclusions: Metformin use was associated with a better PFS and higher CR after SCT in our MM cohort. A trend towards better OS was also noted in the Mt group. Larger studies are needed to enhance our understanding of the clinic effect of metformin on MM. [Table: see text]

3558 Background: Anti-programmed death-1 (PD-1) antibodies have been shown to be effective in the treatment of dMMR CRC. We describe an updated analysis from a cohort of 19 patients (pts) with dMMR CRC treated with pembrolizumab. Methods: Pts were identified through review of the Mayo Clinic electronic medical record (EMR) and chemotherapy administration records from May 2015 through January 2017. All pts with dMMR CRC who received treatment with pembrolizumab were included. The EMR was reviewed to identify demographic, clinical, pathologic and treatment details. Overall survival (OS), progression free survival (PFS) and disease control rate (DCR = CR+PR+SD) are reported. Time to event analysis was calculated using the Kaplan-Meier method. Results: Nineteen pts were included in this analysis; median age at diagnosis was 48.6 years (range 25-93); 53% were female. Most primary tumors were right sided (n = 12; 63%), 6 (32%) were left sided and 1 (5%) was a tumor of unknown primary within the bowel. Twelve (63%) pts received ≥2 lines of therapy prior to pembrolizumab (range 1-4). Five pts received 2 mg/kg every 3 weeks, 11 received 200 mg/day every 3 weeks and 2 pts received 10 mg/kg (1 every 2 weeks, the other every 3 weeks). The most common alterations identified were loss of MLH1 (11/15) and PMS2 (12/15); 4 pts had germline mutations (mut) identified. KRAS mut was identified in 6/16 pts and 2 pts had BRAF mut. Three pts had MLH1 hypermethylation. Median number of cycles of pembrolizumab was 8 (range 1-35+), with 13 (68%) pts receiving ≥6 cycles. DCR at first assessment was 68%, with 5% CR, 47% PR and 16% SD. Median follow-up from diagnosis was 29 months (95% CI 18-42). Median OS was 103 months (95% CI 85-103); 12-month OS was 89%. Median OS from PD-1 therapy was 16.1 months (95% CI 16-NR); 12-month OS from PD-1 therapy was 79%. Median PFS was NR (95% CI 5-NR); 12-month PFS was 54%. At time of analysis, 9 pts remain on PD-1 therapy; 5 pts have died; 3 have received subsequent therapy. Conclusions: Anti-PD1 blockade with pembrolizumab can provide long lasting benefit in dMMR mCRC, even in heavily pretreated pts.

2533 Background: Many cancer clinical trials (CT) lack appropriate representation of specific patients populations, limiting the generalizability of the evidence obtained. Therefore, we determined the representation of ethnic minorities in oncology CT. Methods: Enrollment data from all therapeutic trials reported as completed in clinicaltrial.gov from 2003 to 2016 were analyzed. CT in rare cancers (< 1% incidence) or with recruitment outside of the US were excluded. Enrollment fraction (EF) was defined as the number of enrollees divided by the 2013 SEER database cancer prevalence. Chi-square test was used to estimate differences in categorical data. Results: Out of 1,012 CT, 310 (31%) reported ethnicity with a total of 55689 enrollees. Distribution by race and comparison with data from 1996-2002, US cancer prevalence and US census are described in the Table. Participation in CT varied significantly across ethnic groups, non-Hispanic Whites (NHW) were more likely to be enrolled in CT (EF of 1.2%) than African Americans (EF of 0.7%, p < 0.001) and Hispanics (EF of 0.4%, p<0.001). A decrease in African Americans (AA) and Hispanics (H) enrollment was observed when compared with historical data from 1996 to 2002. Hispanics were less represented in breast and prostate cancer CT contributing only to 3% and 1.5% of the study population; African Americans were less represented in lung (5.4%) and renal cell carcinoma (3%) trials. Asians were well represented and their recruitment doubled over the past 14 years (2% vs 5.3%). Conclusions: African Americans and Hispanics were less likely to be enrolled in CT. Comparing with historical data; we observed a decrease in minorities’ recruitment in the past 14 years. This change could be attributed to the increased complexity of CT and mandatory molecular testing as many minorities lack access to institutions with genetic testing capacity. Future trials should take extra measures to recruit participants that adequately represent the U.S. cancer population. [Table: see text]

Abstract Background: In stage IV non-small cell lung cancer (NSCLC), survival has significantly improved with the use of novel therapies and better supportive care. Despite such trends, it has been noted that patients (pts) frequently refuse cancer treatment. Therefore, we explored the factors associated with treatment refusal in pts with stage IV NSCLC. Methods: Utilizing the National Cancer Database (NCDB), we identified all incident cases with stage IV NSCLC from 2004 to 2014. Patients who received cancer treatment outside of the reporting facility or died before receiving treatment were excluded. Multivariable logistic regression models were used to determine associations with treatment refusal. Results: A total of 341,993 pts were identified. On average, 5.4% of pts refused radiation therapy and 10.3% refused chemotherapy despite provider recommendations. The proportion of pts refusing radiation and chemotherapy increased over the study period from 4.2% to 7.3% and 7.9% to 15%, respectively (p&lt;0.001 for both). In multivariable analysis, men were less likely to refuse radiation or chemotherapy compared to women (OR: 0.82, 95%CI: 0.76-0.83, p&lt;0.001; OR: 0.84, 95%CI: 0.81-0.86, p&lt;0.001, respectively). Factors associated with radiation therapy refusal included: Medicaid or Medicare as primary insurance (OR: 1.95, 95%CI: 1.76-2.15, p&lt;0.001; OR: 1.25, 95%CI: 1.17-1.34, p&lt;0.001, respectively) or a &gt;2 Charlson Comorbidity Index (OR: 1.97, 95%CI: 1.85-2.10, p&lt;0.001). Moreover, receiving care at an academic center (OR: 0.57, 95%CI: 0.53-0.62, p&lt;0.001) was associated with less likelihood of refusing radiation. Regarding chemotherapy, uninsured pts (OR: 2.45, 95%CI: 2.26-2.66, p&lt;0.001), pts with Medicaid as primary insurance (OR: 2.17, 95%CI: 2.03-2.32, p&lt;0.001) or with a high comorbidity index (OR: 1.76, 95%CI: 1.68-1.84, p&lt;0.001) were more likely to refuse chemotherapy. Contrary to findings from previous studies, Non-Hispanic Blacks and Hispanics were less likely to refuse chemotherapy compared to non-Hispanic whites (OR: 0.86, 95%CI: 0.82-0.91, p&lt;0.001; OR: 0.78, 95%CI: 0.72-0.89, p&lt;0.001). Patients receiving care at an academic center and residing in high income neighborhoods were less likely to refuse chemotherapy (OR: 0.76, 95%CI: 0.72-0.80, p&lt;0.001; OR: 0.76, 95%CI: 0.71-0.81, p&lt;0.001, respectively). Distance from residence to treating facility and living in a rural county did not affect treatment refusal. Conclusions: Socioeconomic factors rather than race/ethnicity appear to influence refusal of cancer treatment in pts with stage IV NSCLC in the NCDB. Assessing socioeconomic challenges should be an essential part of patients' evaluation when discussing treatment options. Citation Format: Narjust Duma, Urshila Durani, Ryan Frank, Jonas Paludo, Gustavo Westin, Yanyan Lou, Leventakos Konstantinos, Julian Molina, Ronald Go, Aaron Mansfield, Sikander Ailawadhi, Alex Adjei. Influence of sociodemographic factors on treatment decisions in lung cancer [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 4230.

Abstract Background The treatment of metastatic melanoma has been revolutionized by developments in targeted therapy and immunotherapy. BRAF/MEK inhibitors, blockade of cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death (PD-1/L1) receptor have shown durable anti-melanoma effects. The optimal sequence strategy of targeted therapy and immunotherapy in metastatic BRAF-mutated melanoma patients (pts) is unknown and no treatment guidelines exist. Therefore, we report a single-institution experience of different treatment approaches using targeted therapy and immunotherapy and its impact on outcomes. Methods Pts with BRAF-mutated metastatic melanoma treated with targeted therapy and immunotherapy from 2012 to2017 were analyzed. Six groups were identified based on treatment strategy: (1) 1st line BRAF/MEK inhibitors followed by 2nd line immunotherapy; (1.1) 1st line BRAF/MEK inhibitors followed by 2nd line immunotherapy in combination with BRAF/MEK inhibitors (triple therapy);(1.2) same as group 1 followed by triple therapy as 3rd line; (2) 1st line immunotherapy followed by 2nd line BRAF/MEK inhibitors; (2.1) 1st line immunotherapy followed by 2nd line triple therapy; (2.2) same as group2 followed by triple therapy as 3rd line. All time-to-event analysis was calculated using the Kaplan-Meier method and Wilcoxon test. Results Forty four pts were included. The median age at diagnosis was 49 years (range 21-73), 24 (54%) pts were females and 19 (43%) developed brain metastases during their disease course. BRAF V600 mutation was seen in all pts except in 1 pt with p.N581S mutation. The preferred 1st line targeted therapy was dabrafenib/trametinib used in 17 (94%) out of 18 pts, while ipilimumab was the preferred 1st immunotherapy used in 11 (42%) out of 26 pts. For 2nd line therapy, DT was used in 19 (90%) out of 21 pts, while pembrolizumab was used in 16 (69%) out of 23 pts. For 3rd line, DT was used in 5 (83%) out of 6 pts, while pembrolizumab was used in 6 (100%) out of 6 pts. DT was usually the first choice for patients with high burden disease or brain metastases. The most common approach strategy was immunotherapy followed by targeted therapy (group 2), the median duration of treatment was 11 and 19 weeks respectively; for pts started on targeted therapy followed by immunotherapy (group 1), the median duration of treatment was 17 and 14 weeks respectively. (Table 1) Time-to-next therapy (TTNT) following 1st line treatment was similar in pts treated with targeted therapy (median 23 weeks [95% CI: 15-31]) or immunotherapy (median 26 weeks [95% CI: 10-33], p=0.94). Following 2nd line treatment, the TTNT for pts treated with targeted therapy was 18 weeks (95% CI: 4-38), immunotherapy 18 weeks (95% CI: 13-19) and triple therapy 22 weeks (95% CI: 13-41), p=0.48. A trend towards better overall survival (OS) from frontline therapy was seen in pts who received immunotherapy (1st line) followed by targeted therapy (2nd line) (median 7 years [95% CI: 2.7-7.08]) compared to those who received targeted therapy (1st line) followed by immunotherapy (2nd line) (median 2.3 years [95% CI: 1.3-NR], p=0.09. Interestingly, patients who received salvage chemotherapy had significant longer OS in those treated initially with immunotherapy (median 7 years [95% CI: 3.2-7.08]) (n=6) compared to patients started on targeted therapy (median 2 years [95% CI: 0.6-2.4], p=0.03) (n=5). Conclusion A trend towards longer OS was seen in pts treated with 1st line immunotherapy followed by 2nd line targeted therapy with a median therapy time of 11 and 19 weeks respectively. No difference in TTNT was seen with the use immunotherapy, targeted therapy or triple therapy when used as 1st or 2nd line. The significant longer OS benefit with f 1st line immunotherapy was only seen in patients who received chemotherapy later in their treatment course. Table 1.Treatment Characteristics by GroupMedian duration of therapy in weeksGroup(n)1st line therapy(median)2nd line therapy(median)3rd line therapy(median)Totalmedian (range)Chemotherapy (n)1(n=9)Targeted therapy(17)Immunotherapy (14)N/A52 (13-134)51.1(n=7)Targeted therapy(25)Triple therapy (19)Any*(43)69 (22-118)11.2(n=2)Targeted therapy(60)Immunotherapy (16)Triple therapy (21)96 (81-111)12(n=18)Immunotherapy(11)Targeted therapy(19)Any*(24)48 (16-120)52.1(n=4)Immunotherapy(17)Triple therapy (16)Any*(9)41 (25-69)02.2(n=4)Immunotherapy(19)Targeted therapy(16)Triple therapy (19)61 (54-73)1* include any treatment regimen such as immunotherapy, targeted therapy or chemotherapy Citation Format: Jesus Vera-Aguilera, Jonas Paludo, Narjust Duma, Marcella Tschautscher, Cecilia Yu, Svetomir Markovic. A clinical insight into therapeutic sequence in advanced melanoma [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr LB-A32.