Ronak Saluja

Antiangiogenic Therapy in Advanced Non–small-cell Lung Cancer: A Meta-analysis of Phase III Randomized Trials

Abstract We conducted a meta‐analysis to evaluate the efficacy of adding any antiangiogenic therapy (AT) to the standard of care in advanced non–small‐cell lung cancer (NSCLC). The electronic databases Ovid PubMed, Cochrane Central Register of Controlled Trials, and Embase were searched to identify eligible trials. We included all phase III randomized trials with any line and type of treatment, histology. and AT dose. Pooled hazard ratios (HRs) for overall survival (OS) and progression‐free survival (PFS), and pooled odds ratio (OR) for overall response rates (RR) were calculated. We divided the population into 2 subgroups based on the bevacizumab dose. Data of 19,098 patients from 25 phase III trials were analyzed. Compared with the standard of care, the addition of AT did not prolong OS (HR 0.98; 95% confidence interval [CI], 0.96‐1.00; P = .1 and HR 0.97; 95% CI, 0.94‐1.00; P = .06 for groups 1 and 2, respectively). However, there was a significant improvement in PFS with the addition of AT (HR 0.85; 95% CI, 0.79‐0.91; P < .00001 and HR 0.81; 95% CI, 0.75‐0.88; P < .00001 for groups 1 and 2, respectively) and overall RR (OR 1.61; 95% CI, 1.30‐2.01; P < .0001 and OR 1.72; 95% CI, 1.39‐2.14; P < .00001 for groups 1 and 2, respectively). This is the first meta‐analysis including only all phase III trials with AT in NSCLC showing no significant effect on OS and an improvement in PFS and RR only. The role of AT in advanced NSCLC is still questionable; strong validated biomarkers are eagerly needed to predict which subgroup might benefit the most from such therapy.

Cost-Effectiveness Analysis of Systemic Therapies in Advanced Pancreatic Cancer in the Canadian Health Care System

OBJECTIVES To assess the cost-effectiveness of gemcitabine (G), G + 5-fluorouracil, G + capecitabine, G + cisplatin, G + oxaliplatin, G + erlotinib, G + nab-paclitaxel (GnP), and FOLFIRINOX in the treatment of advanced pancreatic cancer from a Canadian public health payers perspective, using data from a recently published Bayesian network meta-analysis. METHODS Analysis was conducted through a three-state Markov model and used data on the progression of disease with treatment from the gemcitabine arms of randomized controlled trials combined with estimates from the network meta-analysis for the newer regimens. Estimates of health care costs were obtained from local providers, and utilities were derived from the literature. The model estimates the effect of treatment regimens on costs and quality-adjusted life-years (QALYs) discounted at 5% per annum. RESULTS At a willingness-to-pay (WTP) threshold of greater than

A network meta-analysis of the sequencing and types of systemic therapies with definitive radiotherapy in locally advanced squamous cell carcinoma of the head and neck (LASCCHN)☆.

30,666 per QALY, FOLFIRINOX would be the most optimal regimen. For a WTP threshold of

Hepatitis B reactivation in patients with solid tumors: A systematic review and meta-analysis.

50,000 per QALY, the probability that FOLFIRINOX would be optimal was 57.8%. There was no price reduction for nab-paclitaxel when GnP was optimal. CONCLUSIONS From a Canadian public health payers perspective at the present time and drug prices, FOLFIRINOX is the optimal regimen on the basis of the cost-effectiveness criterion. GnP is not cost-effective regardless of the WTP threshold.

Neoadjuvant treatments for locally advanced, resectable esophageal cancer: A network meta-analysis: Neoadjuvant treatments for esophageal cancer

OBJECTIVES The current standard therapy for locally advanced squamous cell carcinoma of the head and neck (LASCCHN) is platinum-based chemotherapy plus concurrent radiotherapy (CRT), but several systemic therapies have been evaluated. We performed a Bayesian network meta-analysis (NMA) with random effects to enable direct and indirect comparisons of all existing treatment modalities for LASCCHN simultaneously. MATERIAL AND METHODS A systematic review was conducted using MEDLINE, EMBASE, ASCO abstracts, ASTRO abstracts and the Cochrane Central of Registered Trials using Cochrane methodology to identify randomized controlled trials (RCTs) up to June 2016. Only abstracts that involved the same definitive radiotherapy in the arms for the RCT were included. RESULTS Sixty-five RCTs involving 13,574 patients and 16 different treatment strategies were identified. Chemotherapy plus concurrent radiation (CRT) was superior to RT with a HR of 0.74 (95%CR 0.69-0.79) for OS in the NMA. Only 3 trials compared RT alone to concurrent therapy with an EGFR antibody (ERT), demonstrating a superior OS (HR 0.75, 95% CR 0.60-0.94), but this difference was not statistically significant when interpreted in a NMA (HR 0.84, 95%CR 0.65-1.08). ERT was not superior to CRT (HR 1.19, 95%CR 0.93-1.54), and the addition of neo-adjuvant taxane-based chemotherapy to CRT was not beneficial (HR 0.86, 95% CR 0.70-1.07). CONCLUSION The addition of either adjuvant or neoadjuvant chemotherapy to the CRT backbone does not confer an OS benefit in the treatment of LASCCHN. Similarly, ERT does not confer an OS benefit for patients who are eligible for CRT.

Do older and younger patients derive similar survival benefits from novel oncology drugs? A systematic review and meta-analysis

138 Background: Hepatitis B virus (HBV) affects over 250 million people worldwide. Most people with chronic HBV (HBsAg positive) have no signs or symptoms of infection. However, when exposed to immunosuppression they are at risk of HBV reactivation which can cause hepatitis, liver failure and death. The risk of HBV reactivation in patients receiving chemotherapy for solid tumors, the efficacy of antiviral prophylaxis, and the clinical impact of HBV reactivation in this setting are uncertain. Primary Aim: To estimate the risk of clinical HBV reactivation (increased HBV DNA + transaminitis) among HBsAg-positive patients administered chemotherapy for a solid tumor. Secondary Aims: To estimate the efficacy of anti-viral prophylaxis and the risk of death from HBV reactivation in patients receiving chemotherapy for solid tumors. METHODS A systematic review and meta-analysis of the English language literature on HBV reactivation was completed (OVID Medline, 1946 to Aug 2013). All citations were reviewed by two or more authors. Data from patients with hematologic malignancies were excluded. Pooled probabilities of HBV reactivation risk, death from HBV reactivation, and odds ratio for the impact of anti-viral prophylaxis were estimated with a random effects model. RESULTS 2,667 citations were identified; 19 were eligible for inclusion. The pooled estimate for clinical HBV reactivation in HBsAg-positive patients receiving chemotherapy for a solid tumor was 21.9% (95% CI; 16.5% to 27.3%) in those not receiving anti-viral prophylaxis, and 2.4% (95% CI 0.7% to 4.2%) in those receiving anti-viral prophylaxis. The odds ratio for clinical HBV reactivation with antiviral prophylaxis compared to no prophylaxis was 0.12 (95% CI 0.06 to 0.25). In the absence of viral prophylaxis, the risk of dying from HBV reactivation in HBsAg-positive solid tumor patients was estimated at 1.3% with a 95% CI of 0.3% to 2.3%. CONCLUSIONS Patients with chronic HBV who are administered chemotherapy for a solid tumor appear to be at substantial risk of clinical HBV reactivation; this risk may be mitigated by anti-viral prophylaxis. In the absence of anti-viral therapy, patients may experience a small but important risk of dying from HBV reactivation.

Examining Trends in Cost and Clinical Benefit of Novel Anticancer Drugs Over Time

The relative survival benefits and postoperative mortality among the different types of neoadjuvant treatments (such as chemotherapy only, radiotherapy only or chemoradiotherapy) for esophageal cancer patients are not well established. To evaluate the relative efficacy and safety of neoadjuvant therapies in resectable esophageal cancer, a Bayesian network meta‐analysis was performed. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched for publications up to May 2016. ASCO and ASTRO annual meeting abstracts were also searched up to the 2015 conferences. Randomized controlled trials that compared at least two of the following treatments for resectable esophageal cancer were included: surgery alone, surgery preceded by neoadjuvant chemotherapy, neoadjuvant radiotherapy or neoadjuvant chemoradiotherapy. The primary outcome assessed from the trials was overall survival. Thirty‐one randomized controlled trials involving 5496 patients were included in the quantitative analysis. The network meta‐analysis showed that neoadjuvant chemoradiotherapy improved overall survival when compared to all other treatments including surgery alone (HR 0.75, 95% CR 0.67–0.85), neoadjuvant chemotherapy (HR 0.83. 95% CR 0.70–0.96) and neoadjuvant radiotherapy (HR 0.82, 95% CR 0.67–0.99). However, the risk of postoperative mortality increased when comparing neoadjuvant chemoradiotherapy to either surgery alone (RR 1.46, 95% CR 1.00–2.14) or to neoadjuvant chemotherapy (RR 1.58, 95% CR 1.00–2.49). In conclusion, neoadjuvant chemoradiotherapy improves overall survival but may also increase the risk of postoperative mortality in patients locally advanced resectable esophageal carcinoma.

High prevalence of potential drug-drug interactions in patients with castration-resistant prostate cancer treated with abiraterone acetate.

Background older patients are commonly believed to derive less benefit from cancer drugs, even if they fulfil clinical trial eligibility [Talarico et al. (2004, J Clin Oncol, 22(22):4626-31)]. We aim to examine if novel oncology drugs provide differential age-based treatment outcomes for patients on clinical trials. Methods a systematic review of randomised control trials (RCTs) cited for clinical efficacy evidence in novel oncology drug approvals by the Food and Drug Administration, European Medicines Agency and Health Canada between 2006 and 2017 was conducted. Studies reporting age-based subgroup analyses for overall or progression-free survival (OS/PFS) were included. Hazard ratios (HRs) and confidence intervals (CIs) for age-based subgroups were extracted. Meta-analyses with random effects were conducted, examining patient subgroups <65 and ≥65 years separately and pooled HRs of studies primary endpoints (OS or PFS) compared to examine if differences existed between age-based subgroups. Sensitivity analyses were conducted for cancer type, primary endpoint and systemic treatment. Results one-hundred-two RCTs, including 65,122 patients, met the inclusion criteria. One study reported age-based toxicity and none reported age-based quality of life (QOL) results. Pooled HRs [95% CIs] for patients <65 and ≥65 years were 0.61 [0.57-0.65] and 0.65 [0.61-0.70], respectively, with no difference between them (P = 0.14). Sensitivity analyses revealed similar results. Conclusion our results suggest that older and young patients, who fulfil clinical trial eligibility, may derive similar relative survival benefits from novel oncology drugs. There is, however, a need to report age-based toxicity and QOL results to support patient discussions regarding the balance of treatment benefit and harm, to encourage informed decision-making.

A network meta-analysis of the sequencing and types of systemic therapies with definitive radiotherapy in locally advanced squamous cell carcinoma of head and neck (LASCCHN).

PURPOSE The purpose of this study was to determine if clinical benefits of novel anticancer drugs, measured by the ASCO Value Framework and European Society of Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale, have increased over time in parallel with increasing costs. METHODS Anticancer drugs from phase III randomized controlled trials cited for clinical efficacy evidence in drug approvals between January 2006 to December 2015 were identified and scored using both frameworks. For each drug, the monthly price and incremental anticancer drug costs were calculated. Relationships between cost and year of approval were examined using generalized linear regressions models. Ordinary least square models were used to evaluate relationships between ASCO and ESMO scores and year of approval. Spearman correlation coefficients between costs and clinical benefit scores were calculated. RESULTS In total, 42 randomized controlled trials were included. Both monthly prices and incremental anticancer drug costs were significantly associated with year of approval and showed an average annual increase of 9% and 21%, respectively. The predicted mean incremental anticancer drug cost increased from

Examining the relationship between cost of novel oncology drugs and their clinical benefit over time.

30,447 in 2006 to