Patients with metastatic renal cell carcinoma (mRCC) who do not meet eligibility criteria for clinical trials have worse outcomes on targeted therapy compared with eligible patients. In fact, extrapolating results of clinical trials to ineligible patients leads to inferior response rates (RRs), progression-free survival (PFS), and overall survival (OS).
“Many patients in everyday practice do not meet eligibility for clinical trials, yet they receive the same targeted therapies as those in clinical trials. Our study shows that ineligible patients have worse outcomes and 1.5 times greater risk of death on the same therapies compared with eligible patients. These findings suggest that these discrepancies should be taken into account when we consider using protocol therapies in protocol-ineligible patients. We need to temper our enthusiasm,” said lead author Daniel Yick Chin Heng, MD, Tom Baker Cancer Centre, University of Calgary, Alberta, Canada. Heng presented the study results at the 2012 ASCO Genitourinary Cancers Symposium.
The study included 894 ineligible patients and 1182 eligible patients with mRCC consecutively treated with VEGF-targeted therapy at 17 international cancer centers. Patients were deemed ineligible retrospectively according to common exclusion criteria for clinical trials. All other patients were assumed to be eligible.
Patients received a variety of anti-VEGF tyrosine kinase inhibitors, including sunitinib, sorafenib, bevacizumab, pazopanib, and axitinib. The most common exclusion criteria were Karnofsky performance status <70% (13.4%), nonclear cell histology (11.2%), brain metastasis (8.3%), and hemoglobin 9 g/dL (7.4%). Patients in the ineligible group were much more likely to be poor risk, and fewer had undergone nephrectomy compared with eligible patients.
Overall response rate was 27%. RR was 34% in favorable-risk patients, 28% in intermediate-risk patients, and 19% in poor-risk patients. RRs were uniformly lower in ineligible patients than eligible patients for every risk category.
Median PFS was 8.6 months for eligible patients and 5.2 for ineligible patients (P <.0001); median PFS when these drugs were used as second-line therapy was 4.4 months and 3.2 months, respectively (P = .0074). Median OS was 28.8 months versus 14.5 months, respectively (P <.0001). “Specific trials should be undertaken to address the needs of protocol-ineligible patients and assess overall survival,” he said.