Angiogenesis inhibitor therapies for metastatic renal cell carcinoma: effectiveness, safety and treatment patterns in clinical practice‐based on medical chart review

Abstract

Study Type – Symptom prevalence (case series) Level of Evidence 4 OBJECTIVE To assess the effectiveness, safety, and treatment patterns of anti‐angiogenic agents in metastatic renal cell carcinoma (mRCC) in tertiary clinical practice settings. PATIENTS AND METHODS We retrospectively reviewed the medical records in two tertiary oncology centres in the USA for all patients treated while off clinical trials from April 2003 to June 2008 who met the entry criteria and received one or more prescriptions for sunitinib or sorafenib, or one or more intravenous administrations of bevacizumab (off‐label) as first‐line anti‐angiogenic treatment. The objective response rate (ORR) reviewed by independent physicians, adverse events (AEs), and treatment modifications were assessed. RESULTS Among 144 patients receiving sunitinib (57), sorafenib (62) and bevacizumab (25), the median treatment duration was 10.5, 8.1 and 7.9 months, and the ORR was 37%, 9% and 13%, respectively. The ORR was lower for patients with metastases to bone, brain, lungs or lymph nodes. Common AEs (all grades) for sunitinib were fatigue (53%), diarrhoea (37%); for sorafenib, diarrhoea (50%), fatigue (40%); for bevacizumab, fatigue (40%), nausea (24%). In all, 34 (60%), 51 (82%) and 20 (80%) patients receiving sunitinib, sorafenib and bevacizumab, respectively, discontinued treatment; 10 (18%), 11 (18%) and four (16%) discontinued due to AEs; 21%, 40% and 12% had a dose interruption, and 30%, 35% and 0% had a dose reduction. CONCLUSIONS Currently available anti‐angiogenic agents had considerable effectiveness in clinical practice. However, the response rates appeared to be low in certain subgroups, but sample sizes were small. Patients had significant rates of AEs, many of which led to treatment modifications. The findings from this retrospective study suggest that there is a need for better‐tolerated therapies for mRCC.

Activity and safety of sunitinib in poor risk metastatic renal cell carcinoma patients

“…Although grade 1 and 2 AE might have been underreported, a high proportion (39.6%) of patients experienced grade 3 or higher AEs. In our series, the rates of grade ≥3 fatigue, nausea, vomiting, and diarrhea are higher than those previously reported in both controlled and non-controlled studies (Table-4) (8)(9)(10)(11)(12). The high proportion of serious AE might be explained by the broader eligibility criteria.…”

“…Some of the included patients had poor KPS (60-70), which are commonly treated under routine care, albeit excluded from randomized clinical trials (13). Furthermore, our analysis showed that 26.4% of patients discontinued sunitinib due to AE, which is higher than rates of 8-20% in other studies (9,10,14). In this study, 30.2% of our patients started at the standard dose of standard dose of sunitinib.…”

Persistence and Compliance Among U.S. Patients Receiving Pazopanib or Sunitinib as First-Line Therapy for Advanced Renal Cell Carcinoma: A Retrospective Claims Analysis

“…Wide-ranging median durations of treatment have been observed in retrospective studies of oral RCC treatments: 4-7 months for pazopanib, 15,20 3-11 months for sunitinib, [31][32][33][34] 4-8 months for sorafenib, 32-35 and 8-10 months for bevacizumab. 34,35 In the clinical trial that demonstrated pazopanib was noninferior to sunitinib with regard to PFS, the median duration of exposure to the study drugs was 8 months for pazopanib and 8 months for sunitinib.…”

“…34,35 In the clinical trial that demonstrated pazopanib was noninferior to sunitinib with regard to PFS, the median duration of exposure to the study drugs was 8 months for pazopanib and 8 months for sunitinib. 36 Factors influencing duration of treatment have not been consistently studied.…”

Risk factors and model for predicting toxicity‐related treatment discontinuation in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor–targeted therapy: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

“…9,10 Real-life experience in clinical practice has identified an increased incidence of toxicity-related treatment discontinuation (TrTD) associated with VEGF-targeted therapies in comparison with initial reports from clinical trials. [11][12][13][14] The careful characterization of patients who are at increased risk for severe toxicities and TrTD can help to establish expectations for patients and physicians and allow more aggressive prophylactic measures to prevent toxicity in high-risk patients. It can assist clinicians in providing clinical benefits from anti-VEGF therapies without compromising patients' quality of life.…”