Once-weekly versus twice-weekly bortezomib in newly diagnosed multiple myeloma: a real-world analysis.

Induction regimens for multiple myeloma (MM) commonly include bortezomib, which has typically been administered twice weekly despite studies demonstrating comparable efficacy and less peripheral neuropathy (PN) with once-weekly bortezomib. We aimed to analyze the real-world prevalence and efficacy of once-weekly versus twice-weekly bortezomib regimens in newly diagnosed MM. We analyzed 2497 US patients aged 18-70 years treated with commercial first-line bortezomib using nationwide Flatiron Health electronic health record-derived data, including 910 (36.4%) patients who received twice-weekly and 1522 (63.2%) who received once-weekly bortezomib. Once-weekly bortezomib use increased over time, from 57.7% in 2017 to 73.1% in 2022. Multivariate analysis identified worsened performance status and more recent year of diagnosis with higher odds of receiving once-weekly bortezomib. Real-world progression-free survival (median 37.2 months with once-weekly versus 39.6 months with twice-weekly, p = 0.906) and overall survival (medians not reached in either cohort, p = 0.800) were comparable. PN rates were higher in patients receiving twice-weekly bortezomib (34.7% versus 18.5%, p < 0.001). In conclusion, once-weekly bortezomib is clearly associated with similar efficacy and fewer toxicities compared to twice-weekly bortezomib. Our findings support once-weekly bortezomib as a standard-of-care regimen for newly diagnosed patients with MM.

Survival outcomes with warfarin compared with direct oral anticoagulants in cancer-associated venous thromboembolism in the United States: A population-based cohort study.

BACKGROUND: Direct oral anticoagulants (DOACs) have comparable efficacy with low-molecular-weight heparin (LMWH) for the treatment of cancer-associated venous thromboembolism (VTE). Whether there is a mortality benefit of DOACs compared with warfarin in the management of VTE in cancer is not established. METHODS AND FINDINGS: Utilizing the United States' Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases from 2012 through 2016, we analyzed overall survival in individuals diagnosed with a primary gastric, colorectal, pancreas, lung, ovarian, or brain cancer and VTE who received a prescription of DOAC or warfarin within 30 days of VTE diagnosis. Patients were matched 1:2 (DOAC to warfarin) through exact matching for cancer stage and propensity score matching for age, cancer site, cancer stage, and time interval from cancer to VTE diagnosis. The analysis identified 4,274 patients who received a DOAC or warfarin for the treatment of VTE within 30 days of cancer diagnosis (1,348 in DOAC group and 2,926 in warfarin group). Patients were of median age 75 years and 56% female. Within the DOAC group, 1,188 (88%) received rivaroxaban, and 160 (12%) received apixaban. With a median follow-up of 41 months, warfarin was associated with a statistically significantly higher overall survival compared to DOACs (median overall survival 12.0 months [95% confidence interval (CI): 10.9 to 13.5] versus 9.9 months [95% CI: 8.4 to 11.2]; hazard ratio (HR) 0.85; 95% CI: 0.78 to 0.91; p < 0.001). Observed differences in survival were consistent across subgroups of cancer sites, cancer stages, and type of VTE. The study limitations include retrospective design with potential for unaccounted confounders along with issues of generalizability beyond the cancer diagnoses studied. CONCLUSIONS: In this analysis of a population-based registry, warfarin was associated with prolonged overall survival compared to DOACs for treatment of cancer-associated VTE.

Overall survival with warfarin vs. low-molecular-weight heparin in cancer-associated thrombosis.

BACKGROUND: When compared with warfarin, low-molecular-weight heparin (LMWH) reduces the incidence of recurrent venous thromboembolism (VTE) in cancer. However, a survival benefit of LMWH over warfarin for the treatment of cancer-associated VTE has not been established. METHODS: Using the Surveillance, Epidemiology and End Results and Medicare linked database from 2007 through 2016, we identified Medicare beneficiaries (aged ≥66 years) who were: (1) diagnosed with primary gastric, colorectal, pancreatic, lung, ovarian, or brain cancer; (2) diagnosed with cancer-associated VTE; and (3) prescribed LMWH or warfarin within 30 days. The primary outcome was overall survival (OS). Patients were matched 1:1 using exact matching for cancer stage and propensity score matching for cancer diagnosis, age, year of VTE, and time from cancer diagnosis to index VTE. Cox proportional-hazards regression was performed to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS: A total of 9706 patients were included. Warfarin was associated with a significant improvement in OS compared with LMWH (median OS, 9.8 months [95% CI, 9.1-10.4] vs. 7.2 months [95% CI, 6.8-7.8]; HR, 0.86; 95% CI 0.83-0.90; p < .001). The survival advantage was most pronounced in pancreatic (HR 0.82 [95% CI, 0.74-0.90], p < .001) and gastric cancers (HR 0.82 [95% CI, 0.68-0.98], p = .03). The observed differences in survival were consistent across subgroups including cancer stage, age, comorbidity burden, and year of VTE. CONCLUSIONS: In this population-based study, warfarin was associated with improved OS compared with LMWH for the treatment of cancer-associated VTE.

Cases of ROS1-rearranged lung cancer: when to use crizotinib, entrectinib, lorlatinib, and beyond?

ROS1-rearranged (also known as ROS1 fusion-positive) non-small-cell lung cancer is an uncommon but distinct molecular subgroup seen in approximately 1-2% of cases. Oncogene addiction due to constitutive ROS1 tyrosine kinase activation has allowed development of molecularly targeted therapies with remarkable anti-tumor activity. Both crizotinib and entrectinib, multitargeted tyrosine kinase inhibitors (TKIs) have now received approval by the FDA for treatment of patients with advanced ROS1-rearranged lung cancers; however, the clinical efficacy and safety of these drugs have been derived from expansion cohorts of single-arm phase I or basket clinical trials with relatively small populations of this clinically and molecularly distinct subgroup. Both drugs lead to high objective response rates (approximately 70-80%) and have manageable side effects, although only entrectinib has potent intracranial efficacy. Lorlatinib is an oral brain-penetrant ALK/ROS1 TKI with activity in both TKI-naïve and some crizotinib-resistant settings (albeit with limited potency against the crizotinib/entrectinib-resistant ROS1-G2032R mutation). We describe cases of advanced ROS1-rearranged lung cancer receiving crizotinib, entrectinib, and/or lorlatinib in first and later line treatment settings to dissect the current state of evidence supporting management decisions for these patients. The next generation ROS1 TKIs (repotrectinib and DS-6051b), owing to their broad activity against kinase mutations including ROS1-G2032R in preclinical studies, hold promise to transform the current treatment paradigm and permit even further gains with regards to long-term outcomes in this subset of patients.

BCR-ABL inhibitors: updates in the management of patients with chronic-phase chronic myeloid leukemia.

OBJECTIVES: This article reviews recent clinical experiences with first-line and second-line second-generation BCR-ABL inhibitors and discusses considerations for selection of therapy for patients with chronic-phase chronic myeloid leukemia. METHODS: We reviewed recent publications on PubMed and abstracts from major congresses relevant to the topic. RESULTS: Therapeutic options for front-line treatment have increased with the approval of two second-generation BCR-ABL inhibitors, dasatinib and nilotinib. Both agents are also treatment options for patients with resistance or intolerance to front-line imatinib. More recently, bosutinib, ponatinib, and omacetaxine have also been approved for patients with resistance or intolerance to prior therapy. DISCUSSION: Expanded treatment options coupled with rapidly changing treatment guidelines have led to numerous questions regarding the selection and monitoring of therapy. Common concerns include how to best select therapy based upon patient-specific comorbidities, monitoring and interpretation of treatment outcomes, and optimization of dosing when side effects occur.