Naveen S. Basappa

Gastric Acid Suppression Is Associated With Decreased Erlotinib Efficacy in Non–Small-Cell Lung Cancer

BACKGROUND Erlotinib is a key therapy for advanced NSCLC. Concurrent AS therapy with TKIs might reduce TKI plasma levels. Because of gastroesophageal reflux disease prevalence, this retrospective analysis was undertaken to determine if coadministering erlotinib with AS therapy affected NSCLC outcomes. PATIENTS AND METHODS Records of advanced NSCLC patients who received erlotinib from 2007 to 2012 at a large, centralized, cancer institution were retrospectively reviewed. Pertinent demographic data were collected and concomitant AS treatment was defined as AS prescription dates overlapping with ≥ 20% of erlotinib treatment duration. Records of patients who received erlotinib for ≥ 1 week were analyzed for progression-free survival (PFS) and overall survival (OS). RESULTS Stage IIIB/IV NSCLC patients (n = 544) were identified and 507 had adequate data for review. The median age was 64 years and 272 were female. Adenocarcinoma (n = 318; 64%) and squamous (n = 106; 21%) were predominant subtypes; 124 patients received concomitant AS therapy. In this unselected population, median PFS and OS in AS versus no AS groups were 1.4 versus 2.3 months (P < .001) and 12.9 versus 16.8 months (P = .003), respectively. Factoring sex, subtype, and performance status in multivariate Cox proportional hazards ratios for PFS and OS between AS and no AS groups were 1.83 (95% confidence interval [CI], 1.48-2.25) and 1.37 (95% CI, 1.11-1.69), respectively. CONCLUSION This large population-based study suggests erlotinib efficacy might be linked with gastric pH and OS could be adversely affected. To our knowledge, this is the first study demonstrating a possible negative clinical effect of coadministration of erlotinib with AS therapy. Further prospective investigation is warranted.

First-line sunitinib or pazopanib in metastatic renal cell carcinoma: The Canadian experience

INTRODUCTION Clinical trial data has shown pazopanib to be non-inferior in overall survival (OS) compared to sunitinib as first-line treatment for metastatic renal cell carcinoma (mRCC). The purpose of this study was to evaluate outcomes and compare dose-modifying toxicities of mRCC patients treated with suntinib or pazopanib in the real-world setting. METHODS Data were collected on mRCC patients using the prospective Canadian Kidney Cancer Information System (CKCis) database from January 2011 to November 2015. Statistical analyses were performed using Cox regression adjusted for several risk factors and the Kaplan-Meier method. RESULTS We identified 670 patients treated with sunitinib (n=577) and pazopanib (n=93). There were no significant differences in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups (p=0.807). Patients treated with sunitinib had improved OS compared with pazopanib (median 31.7 vs. 20.6 months, p=0.028; adjusted hazard ratio [aHR] 0.60; 95% confidence interval [CI] 0.38-0.94). Time to treatment failure (TTF) was numerically, but not statistically, improved with sunitinib (medians 11.0 vs. 8.4 months, p=0.130; aHR 0.87; 95% CI 0.59-1.28). Outcomes with individualized dosing on sunitinib were unavailable for this analysis. Patients treated with sunitinib had a higher incidence of mucositis, hand-foot syndrome, and gastroesophageal reflux disease; patients treated with pazopanib had a higher incidence of hepatotoxicity. CONCLUSIONS In Canadian patients with mRCC, treatment with sunitinib appears to be associated with an improved OS compared to pazopanib in the first-line setting. Patient selection factors and the contemporary practice of individualized dosing with sunitinib may contribute to these real-world outcomes and warrant further investigation.

Setting Research Priorities for Kidney Cancer

Defining disease-specific research priorities in cancer can facilitate better allocation of limited resources. Involving patients and caregivers as well as expert clinicians in this process is of value. We undertook this approach for kidney cancer as an example. The Kidney Cancer Research Network of Canada sponsored a collaborative consensus-based priority-setting partnership that identified ten research priorities in the management of kidney cancer. These are discussed in the context of current initiatives and gaps in knowledge.

Kidney Cancer Research Network of Canada (KCRNC) consensus statement on the role of adjuvant therapy after nephrectomy for high-risk, non-metastatic renal cell carcinoma: A comprehensive analysis of the literature and meta-analysis of randomized controlled trials

INTRODUCTION The Kidney Cancer Research Network of Canada (KCRNC) collaborated to prepare this consensus statement about the use of target agents as adjuvant therapy in patients with non-metastatic renal cell carcinoma (nmRCC) after nephrectomy. We reviewed the published data and performed a meta-analysis of studies that focused on vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). METHODS A systematic literature search identified seven trials on adjuvant target therapy in nmRCC. Three trials, the ASSURE, S-TRAC, and PROTECT, focused on VEGFR TKIs and represented the focus of the study, including a meta-analysis combining their data on disease-free survival (DFS) and overall survival (OS). RESULTS The ASSURE trial showed no DFS or OS benefit of TKIs over placebo after one year of adjuvant sorafenib or sunitinib. In contrast, the S-TRAC trial showed improved DFS after one year of adjuvant sunitinib using central review process, but not using investigator review process. No OS benefit was recorded in either study. Recently, the PROTECT trial also showed no DFS or OS benefit when one year of adjuvant pazopanib was compared to placebo. Meta-analyses of the pooled DFS and OS estimates from all three trials resulted in DFS and OS hazard ratios of 0.87 (95% confidence interval [CI] 0.73-1.04) and 1.04 (95% CI 0.89-1.22), respectively. CONCLUSIONS Data from three available clinical trials of adjuvant VEGFR TKIs vs. placebo do not currently support the use of adjuvant TKI therapy as standard of care after nephrectomy for nmRCC. At this time, adjuvant TKI-based adjuvant therapy is not recommended for routine use after nephrectomy for high-risk nmRCC, but highly motivated patients may benefit from a discussion with their oncologist regarding the risks and benefits of adjuvant TKI.

PD57-08 CENTRALIZATION OF RADICAL CYSTECTOMY FOR BLADDER CANCER IN A UNIVERSAL HEALTHCARE SYSTEM: EARLY RESULTS FROM A CANADIAN ACADEMIC CENTER

and diagnosis of bladder cancer controlling for age, smoking history and race. RESULTS: We identified 42,774 patients with BPH. The median follow-up was 87 months. There were 11,864 (27.7%) African Americans (AA), 11,863 (27.7%) Caucasians, and 6,340 (14.8%) Hispanics in this population. 5,698 (13.3%) patients were prescribed Finasteride. Bladder cancer was diagnosed in 84 of 5,698 (1.5%) patients who were prescribed Finasteride compared with 863 of 37,076 (2.3%), who were not prescribed Finasteride (p<0.001). Multivariate logistic regression analysis showed that Finasteride use was protective of bladder cancer (OR: 0.57, CI: 0.45-0.71, p<0.001). When we stratified the data based on race, Finasteride use was protective of bladder cancer in Caucasians (2.1% vs. 3.8%, p1⁄40.001) and Hispanics (0.8% vs. 1.6%, p1⁄40.042), but not in AA (1.7% vs. 1.7%, p1⁄40.854). CONCLUSIONS: Our study confirms previous findings from the PLCO study that men who are on Finasteride have lower incidence of bladder cancer but only in Caucasians and Hispanics. Future research and randomized controlled studies may be needed to confirm these findings.

The kidney cancer research priority-setting partnership: Identifying the top 10 research priorities as defined by patients, caregivers, and expert clinicians

It is critically important to define disease-specific research priorities to better allocate limited resources. There is growing recognition of the value of involving patients and caregivers, as well as expert clinicians in this process. To our knowledge, this has not been done this way for kidney cancer. Using the transparent and inclusive process established by the James Lind Alliance, the Kidney Cancer Research Network of Canada (KCRNC) sponsored a collaborative consensus-based priority-setting partnership (PSP) to identify research priorities in the management of kidney cancer. The final result was identification of 10 research priorities for kidney cancer, which are discussed in the context of current initiatives and gaps in knowledge. This process provided a systematic and effective way to collaboratively establish research priorities with patients, caregivers, and clinicians, and provides a valuable resource for researchers and funding agencies.

Treatment options in advanced renal cell carcinoma after first-line treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitors

Targeted therapy for metastatic renal cell carcinoma (mRCC) was introduced a decade ago and since then, a number of therapeutic options have been developed. Vascular endothelial growth factor-targeted therapy is the widely accepted first-line option for mRCC. After progression, treatment in the second-line setting has typically been with either axitinib or everolimus. However, with the advent of several new agents demonstrating efficacy in the second-line setting, including nivolumab, cabozantinib, and the combination of lenvatinib and everolimus, the treatment paradigm has shifted toward these novel therapies with improved patient outcomes.

Perioperative chemotherapy for muscle invasive bladder cancer.

Purpose of reviewRadical cystectomy with or without systemic chemotherapy is considered a standard of care for patients with muscle invasive bladder cancer (MIBC). The purpose of this review is to provide an update on current and recent literature published within the last 12 months reviewing the evidence for use of perioperative chemotherapy for patients with MIBC. Recent findingsIn the neoadjuvant chemotherapy (NAC) setting, the evidence demonstrates clinical efficacy and lower rate of toxicity with the use of high-dose methotrexate, vinblastine, doxorubicin, and cyclophosphamide (MVAC) compared with standard MVAC. Higher quality evidence for the use of gemcitabine with cisplatin is not yet available. Meta-analysis of cisplatin-based regimens in the adjuvant setting demonstrates significant benefit in overall survival and disease-free survival specifically in patients with lymph-node-positive disease. SummaryThe available evidence suggests that along with radical cystectomy, cisplatin-based perioperative chemotherapy should be the standard of care in patients with MIBC with a higher quality and quantity of literature in support of the NAC approach. Adoption of perioperative chemotherapy for MIBC is on the rise in North America, which is reassuring. Novel therapeutic approaches for cisplatin-ineligible patients are currently being investigated.