Citations

186 Background: The optimal sequence strategy of BRAF/MEK inhibitors, anti-PD- 1/PDL-1 and anti-CTLA-4 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 (TT) and immunotherapy and its impact on outcomes. Methods: BRAF-mutated metastatic melanoma pts treated with TT and immunotherapy from 2012 to2017 were analyzed. Six groups were identified based on treatment strategy. All time-to-event analyses were calculated using the Kaplan-Meier method and Wilcoxon test. Results: Forty-four pts were identified. The median age at diagnosis was 49 years (range 21-73), 54% pts were females and 43% developed brain metastases during disease course. The most common approach strategy was immunotherapy followed by TT, the median duration of treatment was 11 and 19 weeks, respectively. Time-to-next therapy (TTNT) following 1st line treatment was similar in pts treated with TT (median 23 weeks [95% CI: 15-31]) or immunotherapy (median 26 weeks [95% CI: 10-33], p = 0.94). A trend towards better overall survival (OS) was seen in pts who received immunotherapy followed by TT (p = 0.09); patients who received salvage chemotherapy (carboplatin/paclitaxel) had significantly longer OS (median 7 years [95% CI: 3.2-7.08]) ( p = 0.03). Conclusions: No differences in TTNT were seen with immunotherapy, TT or combined (triple therapy) when used as 1st or 2nd line. The significant longer OS benefit with 1st line immunotherapy was only seen in patients who received chemotherapy later in their treatment course. [Table: see text]

Purpose: Many cancer clinical trials lack appropriate representation of specific patient populations, limiting their generalizability. Therefore, we determined the representation of ethnic minorities and women in cancer clinical trials. Methods: Enrollment data from all therapeutic trials reported as completed in ClinicalTrials.gov from 2003 to 2016 were analyzed. We calculated enrollment fractions (EFs) for each group, defined as the number of enrollees divided by the 2013 Surveillance, Epidemiology, and End Results (SEER) database cancer prevalence. Results: Of 1,012 clinical trials, 310 (31%) reported ethnicity with a total of 55,689 enrollees. Participation varied significantly across ethnic groups. Non-Hispanic whites were more likely to be enrolled in clinical trials (EF, 1.2%) than African Americans (EF, 0.7%; P < .001) and Hispanics (EF, 0.4%; P < .001). A decrease in African American (6% v 9.2%) and Hispanic (2.6% v 3.1%) enrollment was observed when compared with historical data from 1996 to 2002. Younger patients (age younger than 65 years) were more likely to be enrolled in clinical trials than the elderly (64% v 36%; P < .001). Low recruitment of female patients was observed in clinical trials for melanoma (35%), lung cancer (39%), and pancreatic cancer (40%). Conclusion: We observed a decrease in recruitment of minorities over the past 14 years compared with historical data. African Americans, Hispanics, and women were less likely to be enrolled in cancer clinical trials. Future trials should take extra measures to recruit participants that adequately represent the US cancer population.

AbstractWaldenström macroglobulinemia (WM) is an immunoglobulin M‐associated lymphoma, with majority of cases demonstrating MYD88 locus alteration, most commonly, MYD88L265P. Owing to low prevalence of the wild‐type (WT) MYD88 genotype in WM, clinically relevant data in this patient population are sparse, with one study showing nearly a 10‐fold increased risk of mortality in this subgroup compared to patients with MYD88L265P mutation. We studied a large cohort of patients with MYD88L265P and MYD88WT WM, evaluated at Mayo Clinic, Rochester, between 1995 and 2016, to specifically assess the impact of these genotypes on clinical course. Of 557 patients, MYD88L265P mutation status, as determined by allele‐specific polymerase chain reaction, was known in 219, and 174 (79%) of those exhibited MYD88L265P, 157 of 174 patients had active disease. Of 45 (21%) patients with MYD88WT genotype, 44 had active disease. The estimated median follow‐up was 7.0 years; median overall survival was 10.2 years (95% CI: 8.4‐16.5) for MYD88L265P versus 13.9 years (95% CI: 6.4‐29.3) for the MYD88WT (P = 0.86). The time‐to‐next therapy from frontline treatment and the presenting features were similar in the two patient populations. For patients with smoldering WM at diagnosis, the median time‐to‐progression to active disease was 2.8 years (95% CI: 2.2‐3.8) in the MYD88L265P cohort and 1.9 years (95% CI: 0.7‐3.1) in the MYD88WT cohort (P = 0.21). The frequency of transformation to high‐grade lymphoma, or the development of therapy‐elated myelodysplastic syndrome was higher in the MYD88WT cohort (16% versus 4% in the MYD88L265P, P = 0.009). In conclusion, MYD88L265P mutation does not appear to be a determinant of outcome, and its presence may not be a disease‐defining feature in WM. Our findings warrant external validation, preferably through prospective studies.

SummaryThe management of Waldenström macroglobulinaemia (WM) relies predominantly on small trials, one of which has demonstrated activity of dexamethasone, rituximab and cyclophosphamide (DRC) in the frontline setting. We report on the efficacy of DRC, focusing on relapsed/refractory (R/R) patients. Ibrutinib, a recently approved agent in WM demonstrated limited activity in patients with MYD88WT genotype. Herein, we additionally report on the activity of DRC based on the MYD88L265P mutation status. Of 100 WM patients evaluated between January 2007 and December 2014 who received DRC, 50 had R/R WM. The overall response rate (ORR) was 87%. The median progression‐free survival (PFS) and time‐to‐next‐therapy (TTNT) were 32 (95% confidence interval [CI]: 15–51) and 50 (95% CI: 35–60) months, respectively. In the previously untreated cohort (n = 50), the ORR was 96%, and the median PFS and TTNT were 34 months (95% CI: 23–not reached [NR]) and NR (95% CI: 37–NR), respectively. Twenty‐five (86%) of 29 genotyped patients harbored MYD88L265P. The response rates and outcomes were independent of MYD88 mutation status. Grade ≥3 adverse effects included neutropenia (20%), thrombocytopenia (7%) and infections (3%). Similar to the frontline setting, DRC is an effective and well‐tolerated salvage regimen for WM. In contrast to ibrutinib, DRC offers a less expensive, fixed‐duration option, with preliminary data suggesting efficacy independent of the patients’ MYD88 status.

Key Points PVD is an active combination in relapsed lenalidomide-refractory MM patients. PVD with weekly bortezomib offers a simpler, more convenient, and well-tolerated regimen option.

Objectives: Extraskeletal osteosarcoma (EO) is a malignant neoplasm that produces osteoid, bone, and chondroid material without direct attachment to bone or periosteum. Surgical resection is the mainstay of treatment; the role of chemotherapy is not well defined. Therefore, we evaluated the impact of chemotherapy in the survival of patients with EO. Methods: All EO patients seen at Mayo Clinic between 1990 and 2014 were assessed. Forty-three patients were included after all archived pathology slides were reviewed to confirm the diagnosis of EO. Results: Of 43 patients, 37 patients had localized disease and 6 patients had metastatic disease at diagnosis. Chemotherapy was used in 73% and 75% of patients, respectively. Chemotherapy was predominantly anthracycline based, and included platinum in 22 patients (84%). Median overall survival (OS) and progression-free survival (PFS) were 50 months (95% confidence interval, 25-99), and 21 months (95% confidence interval, 13-not reached), respectively. There was a trend towards longer OS and PFS in patients who received chemotherapy. Those who received platinum-based therapy had remarkably prolonged OS (median, 182 vs. 18 mo; 5-year, 61% vs. 0%; P=0.01) and PFS (median, not reached vs. 10 mo; 5-year, 56% vs. 0%; P=0.005). Baseline characteristics were similar in the platinum and nonplatinum group. In patients who received chemotherapy, relapse/recurrence rate was lower in the platinum-based group (41%) as opposed to the nonplatinum-based group (100%; P=0.02). In the neoadjuvant setting, the overall response rate of platinum-containing regimens was 27%. Conclusions: Our results suggest a clinical benefit when platinum-based chemotherapy is incorporated in the management of patients with EO. We plan to validate this further with an expanded multicenter analysis.