Z Zhou

Comparative Efficacy of Ceritinib and Crizotinib as Initial ALK–Targeted Therapies in Previously Treated Advanced NSCLC: An Adjusted Comparison with External Controls

Introduction: Crizotinib and ceritinib have been developed to treat advanced or metastatic NSCLC by inhibiting anaplastic lymphoma receptor tyrosine kinase gene (ALK). No randomized trial has compared these treatments head‐to‐head. We compared efficacy outcomes between patients receiving ceritinib and an external control group receiving crizotinib, both as initial ALK‐targeted therapies for previously treated advanced or metastatic ALK‐positive NSCLC. Methods: Individual patient data for the ceritinib‐treated patients were drawn from two single‐arm trials (ASCEND‐1 and ASCEND‐3); published summary data for the crizotinib‐treated patients were extracted from three trials (PROFILE 1001, PROFILE 1005, and PROFILE 1007). To adjust for cross‐trial differences, average baseline characteristics were matched using propensity score weighting. Overall survival (OS), progression‐free survival (PFS), and overall response rate were then compared between treatment groups. Results: Before matching, the ceritinib‐treated patients (n = 189) were significantly different from the crizotinib‐treated patients (n = 557) in the distribution of race and number of prior regimens. After matching, all available baseline characteristics were balanced. Compared with crizotinib, ceritinib was associated with longer OS (hazard ratio = 0.59, 95% confidence interval: 0.46–0.75) and longer PFS (median 13.8 versus 8.3 months, hazard ratio = 0.52, 95% confidence interval: 0.44–0.62) in Cox proportional hazards models. The 12‐month OS was 82.6% with ceritinib and 66.0% with crizotinib in a Kaplan‐Meier analysis (log‐rank p < 0.001). There was no significant difference in overall response rate between ceritinib and crizotinib. Conclusions: In an adjusted comparison across separate clinical trials, ceritinib was associated with prolonged OS and PFS compared with crizotinib when used as initial ALK‐targeted therapy for previously treated ALK‐positive NSCLC.

An indirect comparison and cost per responder analysis of adalimumab, methotrexate and apremilast in the treatment of methotrexate-naïve patients with psoriatic arthritis

Abstract Objective Apremilast was recently approved for the treatment of active psoriatic arthritis (PsA). However, no studies compare apremilast with methotrexate or biologic therapies, so its relative comparative efficacy remains unknown. This study compared the response rates and incremental costs per responder associated with methotrexate, apremilast, and biologics for the treatment of active PsA. Methods A systematic literature review was performed to identify phase 3 randomized controlled clinical trials of approved biologics, methotrexate, and apremilast in the methotrexate-naïve PsA population. Using Bayesian methods, a network meta-analysis was conducted to indirectly compare rates of achieving a ≥20% improvement in American College of Rheumatology component scores (ACR20). The number needed to treat (NNT) and the incremental costs per ACR20 responder (2014 US

Cost-Effectiveness Of Ceritinib In The Treatment Of Previously Treated Anaplastic Lymphoma Kinase-Positive (Alk+) Non-Small Cell Lung Cancer In The United Kingdom.

) relative to placebo were estimated for each of the therapies. Results Three trials (MIPA for methotrexate, PALACE-4 for apremilast, and ADEPT for adalimumab) met all inclusion criteria. The NNTs relative to placebo were 2.63 for adalimumab, 6.69 for apremilast, and 8.31 for methotrexate. Among methotrexate-naïve PsA patients, the 16 week incremental costs per ACR20 responder were

142PD: The impacts on work productivity from ceritinib compared with chemotherapy for crizotinib-experienced ALK+ non-small cell lung cancer.

3622 for methotrexate,

Association between time to progression and subsequent survival inceritinib-treated patients with advanced ALK-positive non-small-cell lung cancer

26,316 for adalimumab, and

Health resource use and costs of vilazodone and other selective serotonin re-uptake inhibitors in treating major depressive disorder.

45,808 for apremilast. The incremental costs per ACR20 responder were

Medication use in adults with attention deficit/hyperactivity disorder in a commercially-insured population in the United States

222,488 for apremilast vs. methotrexate. Conclusion Among methotrexate-naive PsA patients, adalimumab was found to have the lowest NNT for one additional ACR20 response and methotrexate was found to have the lowest incremental costs per ACR20 responder. There was no statistical evidence of greater efficacy for apremilast vs. methotrexate. A head-to-head trial between apremilast and methotrexate is recommended to confirm this finding.

Economic Burden of Switching to a Non-Tumor Necrosis Factor Inhibitor Versus a Tumor Necrosis Factor Inhibitor Biologic Therapy among Patients with Rheumatoid Arthritis.

Table 1. Sources of efficacy inputs Sources Post-CT Ceritinib Pooled data from ASCEND-1 and ASCEND-3 trials7,9 Comparators Indirect comparison10,11 Post-ALKi Ceritinib Pooled data from ASCEND-1 and ASCEND-2 trials7,8 Docetaxel Shaw AT, et al. (2013)3, Ou SH, et al. (2014)13 Pemetrexed Shaw AT, et al. (2013)3, Ou SH, et al. (2014)13 BSC Shepherd FA, et al. (2005)14, Ou SH, et al. (2014)13 Model Inputs

Systematic Literature Review For Treatment Outcomes (Including Immuno-Oncology Treatment) Among Patients with Stage 3 Unresectable Non-Small Cell Lung Cancer (NSCLC)

Data cut-off 14 Apr 2014 13 Aug 2014 Number of patients with BM at baseline 98 100 Duration of follow-up, months (range) 9.8 (0.1–22.2) 11.2 (0.2–18.9) Whole body response per BIRC Overall response rate, % [95% CI] 41.8 [31.9, 52.2] 32.0 [23.0, 42.1] Disease control rate, % [95% CI] 69.4 [59.3, 78.3] 64.0 [53.8, 73.4] Median duration of responsea, months [95% CI] 8.2 [5.6, 13.1] 9.3 [5.5, 12.9] Median progression-free survival, months [95% CI] 6.7 [5.4, 9.5] 6.8 [5.4, 7.4] Intracranial response per BIRC Pooled Number of patients with measurable BM at baseline 28 33 61 Overall intracranial response rate, % [95% CI] 35.7 [18.6, 55.9] 39.4 [22.9, 57.9] 37.7 [25.6, 51.0] Intracranial disease control rate, % [95% CI] 60.7 [40.6, 78.5] 84.8 [68.1, 94.9] 73.8 [60.9, 84.2] Median intracranial duration of responsea, months [95% CI] 11.1 [2.8, NE] 12.8 [4.0, 13.2] 12.8 [6.9, NE]

Systematic Literature Review of Treatments for Patients with Untreated Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Abstract Objective: Time to progression (TTP) is a surrogate marker of overall survival (OS). However, OS is also dependent on post-progression survival (PPS). This study evaluated the association between TTP and the duration of PPS among adult patients who received ceritinib (Zykadia1) for the treatment of advanced anaplastic lymphoma kinase positive (ALK+) non-small-cell lung cancer (NSCLC). Research design and methods: A pooled analysis was performed on 181 ASCEND-1 (phase I) and ASCEND-2 (phase II) patients who experienced disease progression while on ceritinib. TTP was assessed on its association with PPS in a Kaplan–Meier analysis and in Cox proportional hazard models, adjusted for clinical covariates. Main outcome measures: Main outcomes measured include TTP, PPS, and OS. Results: Patients with TTP ≥6 months experienced significantly longer PPS compared to those with TTP <6 months (median: 9.8 vs. 6.5 months, log-rank p-value < .01). When TTP was assessed as a continuous variable, every 3 months of longer TTP was associated with a 21% lower hazard of death following progression (hazard ratio [HR]: 0.79, 95% confidence interval [CI]: 0.63–1.00; adjusted HR: 0.79, 95% CI: 0.64–0.99). This positive association translated into an OS benefit: each 3 months of longer TTP was associated with a lower hazard of death (adjusted HR: 0.46, 95% CI: 0.37–0.58). Median OS was 20.0 months for patients with TTP ≥6 months and was 10.9 months for patients with TTP <6 months. Conclusions: A longer duration of TTP after treatment with ceritinib was significantly associated with a longer duration of both PPS and OS.