STAYING UP-TO-DATE in the fast-paced world of oncology literature is a daunting task at best. To assist with that task, The ASCO Post has assembled an assortment of studies recently published in the Journal of Clinical Oncology.
Sorafenib Dosing and Outcomes in Hepatocellular Cancer
Kim A. Reiss, MD
IN A RETROSPECTIVE STUDY reported in the Journal of Clinical Oncology, Reiss et al found that reducing the starting dose of sorafenib (Nexavar) was associated with noninferior overall survival, reduced cost, and lower risk of discontinuing treatment in patients with advanced hepatocellular carcinoma.
The study involved data from 4,903 patients from 128 Veterans Health Administration hospitals who were prescribed sorafenib for hepatocellular carcinoma between January 2006 and April 2015. Propensity-score matching (1:1) was used to account for potential treatment bias. Hazard ratios (HRs) were calculated using Cox regression and were tested against a noninferiority margin of HR = 1.1. The primary endpoint was overall survival of patients prescribed the standard starting sorafenib dose of 800 mg/d vs those prescribed a lower starting dose (< 800 mg/d).
Survival and Other Outcomes
Overall, 3,094 patients (63%) received the standard starting dose, and 1,809 (37%) received a reduced starting dose (average starting dose = 367 mg/d). Those receiving a reduced dose were more likely to have Barcelona Clinic Liver Cancer stage D disease (P < .001), higher Model for End- Stage Liver Disease Sodium scores (P < .001), higher Child-Turcotte-Pugh scores (P < .001), and higher Cirrhosis Comorbidity Index scores (P = .01). Without adjustment, the reduced-dose group had poorer median overall survival (median = 200 vs 233 days, HR = 1.10, P = .002). After propensity-score matching and multivariate analysis, no significant difference in overall survival was observed (adjusted HR = 0.92, 95% confidence interval = 0.83–1.01), with the hazard ratio being significantly below the noninferiority margin (P < .001).
Patients receiving reduced starting doses had a significantly lower cumulative sorafenib cost (median = $5,636 vs $8,661, P < .001). After propensity matching, there was a trend toward a reduced likelihood of discontinuing sorafenib due to adverse events in the reduced-dose group (19.6% vs 22.4%, P = .056), including a reduced likelihood of discontinuing treatment due to gastrointestinal adverse events (8.7% vs 10.8%, P = .047).
The investigators concluded: “The initiation of sorafenib therapy at reduced dosages was associated with reduced pill burden, reduced treatment costs, and a trend toward a decreased rate of discontinuing sorafenib because of adverse events. Reduced dosing was not associated with inferior [overall survival] relative to standard dosing.”
The study was supported by Bayer HealthCare Pharmaceuticals, the VA HIV, Hepatitis and Related Conditions Programs in the Office of Specialty Care Services, and a grant from the National Cancer Institute.
Adding Bortezomib to R-CHOP in Non–Germinal Center B-Cell–Like Lymphoma
John P. Leonard, MD
A PHASE II RANDOMIZED TRIAL reported in the Journal of Clinical Oncology by Leonard et al showed no significant progression-free survival benefit of adding bortezomib (Velcade) to R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, and prednisone) in previously untreated patients with non–germinal center B-cell–like (non-GCB) diffuse large B-cell lymphoma (DLBCL).
In the trial, 206 patients from 69 U.S. sites were randomized between October 2009 and July 2013 to receive six 21-day cycles of standard R-CHOP (n = 103) or R-CHOP plus bortezomib at 1.3 mg/m2 on days 1 and 4. The primary endpoint was progression-free survival among the 183 patients (92 in bortezomib group and 91 in the control group) with centrally confirmed non-GCB DLBCL who received at least 1 dose of study drug.
After a median follow-up of 34 months, progression-free survival events had occurred in 18% of the bortezomib group vs 25% of the control group. Median progression-free survival was not reached in either group. Progression-free survival at 2 years was 82.0% vs 77.6% among all evaluable patients (hazard ratio [HR] = 0.73, P = .611), 72.4% vs 65.1% among patients with high-intermediate/high International Prognostic Index (IPI) scores (HR = 0.67, P = .606), and 88.9% vs 90.0% among those with low/ low-intermediate IPI scores (HR = 0.85, P = .958).
Overall response rates were 96% vs 98%. Median overall survival was not reached in either group (HR = 0.75, P = .763). Survival at 2 years was 93.0% vs 88.4% among all patients, 92.1% vs 79.2% among those with high-intermediate/high IPI scores (HR = 0.62, P = .638), and 93.8% vs 97.7% among those with low/low-intermediate scores (HR = 1.02, P = .999).
Grade ≥ 3 adverse events in the bortezomib vs control group included neutropenia in 49% vs 53%, thrombocytopenia in 29% vs 13%, anemia in 15% vs 7%, leukopenia in 25% vs 26%, and neuropathy in 5% vs 1%. Serious adverse events occurred in 34% vs 31%. Treatment was discontinued due to adverse events in 6% vs 4%.
The investigators concluded: “Outcomes for newly diagnosed, prospectively enrolled patients with non-GCB DLBCL were more favorable than expected with R-CHOP and were not significantly improved by adding bortezomib.”
The study was supported by Millennium Pharmaceuticals.
John P. Leonard, MD, of Meyer Cancer Center, Weill Cornell Medicine and NewYork-Presbyterian Hospital, is the corresponding author of the Journal of Clinical Oncology article.