Michiko Iwasaki

Phase II trial of the combination of bevacizumab and erlotinib in patients who have advanced hepatocellular carcinoma

PURPOSE The study objective was to determine the proportion of patients with hepatocellular carcinoma (HCC) treated with the combination of bevacizumab (B) and erlotinib (E) who were alive and progression free at 16 weeks (16-week progression-free survival [PFS16]) of continuous therapy. Secondary objectives included response rate, median PFS, survival, and toxicity. PATIENTS AND METHODS Patients who had advanced HCC that was not amenable to surgical or regional therapies, up to one prior systemic treatment; Childs-Pugh score A or B liver function; Eastern Cooperative Oncology Group performance status 0, 1, or 2 received B 10 mg/kg every 14 days and E 150 mg orally daily, continuously, for 28-day cycles. Tumor response was evaluated every 2 cycles by using Response Evaluation Criteria in Solid Tumors Group criteria. A total of 40 patients were treated. RESULTS The primary end point of PFS16 was 62.5%. Ten patients achieved a partial response for a confirmed overall response rate (intent-to-treat) of 25%. The median PFSevent was 39 weeks (95% CI, 26 to 45 weeks; 9.0 months), and the median overall survival was 68 weeks (95% CI, 48 to 78 weeks; 15.65 months). Grades 3 to 4 drug-related toxicity included fatigue (n = 8; 20%), hypertension (n = 6; 15%), diarrhea (n = 4; 10%) elevated transaminases (n = 4; 10%), gastrointestinal hemorrhage (n = 5; 12.5%), wound infection (n = 2; 5%) thrombocytopenia (n = 1; 2.5%), and proteinuria, hyperbilirubinemia, back pain, hyperkalemia, and anorexia (n = 1 each). CONCLUSION The combination of B + E in patients who had advanced HCC showed significant, clinically meaningful antitumor activity. B + E warrant additional evaluation in randomized controlled trials.

Efficacy of Bevacizumab plus Erlotinib for Advanced Hepatocellular Carcinoma and Predictors of Outcome: Final Results of a Phase II Trial

Objective: A phase II study was performed to evaluate the efficacy and tolerability of bevacizumab and erlotinib in advanced hepatocellular carcinoma (HCC) patients, and to investigate clinical and molecular predictors of outcome. Methods: 59 patients with advanced HCC received 10 mg/kg i.v. of bevacizumab every 14 days and 150 mg p.o. of erlotinib daily. The primary endpoint was progression-free survival (PFS) at 16 weeks. Clinical characteristics and plasma biomarkers expression levels were analyzed. Results: PFS at 16 weeks was 64% (95% CI 51–76): 14 patients achieved partial response (24%), 33 had stable disease (56%), 6 progressed (10%), and 6 were not evaluable (10%). Median overall survival was 13.7 months (95% CI 9.6–19.7), and median PFS was 7.2 months (95% CI 5.6–8.3). Grade 3–4 adverse events included fatigue (30%), diarrhea (17%), hypertension (14%), elevated transaminases (12%), and gastrointestinal hemorrhage (10%). High plasma angiopoietin-2, epidermal growth factor receptor, and endothelin-1, and lack of acneiform rash were associated with poor outcome. Conclusions: The combination of bevacizumab with erlotinib achieved encouraging results in patients with advanced HCC. Current correlatives may help to guide future HCC studies.

Phase II trial of bevacizumab and erlotinib as a second-line therapy for advanced hepatocellular carcinoma

Trial registry Clinicaltrials.gov #NCT01180959. Background Early clinical studies of bevacizumab and erlotinib in advanced hepatocellular carcinoma (HCC) have a tolerable toxicity and a promising clinical outcome. We evaluated the efficacy and tolerability of this combination as a second-line therapy for HCC refractory to sorafenib. Methods For this single-arm, Phase II study, we recruited patients with Child–Pugh class A or B liver disease, Eastern Cooperative Oncology Group performance status 0–2, and advanced HCC that was not amenable to surgical or regional therapies and treatment with sorafenib had failed (disease progressed or patient could not tolerate sorafenib). Patients received 10 mg/kg intravenous bevacizumab every 14 days and 150 mg oral erlotinib daily for 28-day cycles until progression. Tumor response was evaluated every two cycles using Response Evaluation Criteria in Solid Tumors. The primary end point was the 16-week progression-free survival rate. Secondary end points included time to progression and overall survival. Results A total of 44 patients were enrolled and had a median follow-up time of 33.8 months (95% confidence interval [CI]: 23.5 months – not defined). The 16-week progression-free survival rate was 43% (95% CI: 28%–59%), median time to progression was 3.9 months (95% CI: 2.0–8.3 months), and median overall survival duration was 9.9 months (95% CI: 8.3–15.5 months). Grade 3–4 adverse events included fatigue (13%), acne (11%), diarrhea (9%), anemia (7%), and upper gastrointestinal hemorrhage (7%). Conclusion Bevacizumab plus erlotinib was tolerable and showed a signal of survival benefit in the second-line setting for patients with advanced HCC. Because standard-of-care options are lacking in this setting, further studies to identify predictors of response to this regimen are warranted.

Neuroendocrine Tumors and Lanreotide Depot: Clinical Considerations and Nurse and Patient Preferences.

BACKGROUND Somatostatin analogs (SSAs) are a mainstay therapy for the treatment of carcinoid syndrome associated with neuroendocrine tumors (NETs). They are effective for a range of gastroenteropancreatic NETs (GEP-NETs). Lanreotide depot (Somatuline®) is an SSA that is approved for the treatment of GEP-NETs to improve progression-free survival (PFS). OBJECTIVES The article reviews the efficacy, safety, and administration of lanreotide depot and relates those attributes to considerations and preferences of oncology nurses and their patients. METHODS A review of the literature on the use of lanreotide for the treatment of NETs and carcinoid syndrome was conducted. In addition, the literature on drug delivery and routes of administration was surveyed to provide context for comparative studies related to clinical and patient preferences. FINDINGS Lanreotide depot prolongs PFS and is well tolerated by patients who expressed satisfaction in the ability to control symptoms related to carcinoid syndrome. Nurses cited several benefits to using lanreotide depot in the clinical setting, including more time saved to address other patient care issues. Attributes of lanreotide depot-including its efficacy, safety and tolerability, dosing and administration, and cost-may contribute to healthcare decisions regarding the treatment and management of NETs.