Scott Whiting

Quality-adjusted survival with combination nab-paclitaxel + gemcitabine vs gemcitabine alone in metastatic pancreatic cancer: a Q-TWiST analysis

Abstract Objectives: To use the Quality-Adjusted Time Without Symptoms or Toxicities (Q-TWiST) methodology to compare the quality-of-life and survival benefits associated with the combination of albumin-bound (nab)-paclitaxel and gemcitabine vs gemcitabine alone in the first-line treatment of metastatic pancreatic adenocarcinoma. Methods: Total survival time through 45 months was partitioned into time before disease progression without toxicity grade ≥3 (TWiST), time with adverse event grade ≥3 (TOX), and time of disease progression (REL). Mean Q-TWiST was calculated by multiplying time spent in each health state by its respective utility (i.e., TWiST = 1.00; TOX/REL = 0.50, 0–1 in sensitivity analyses). Non-parametric bootstrap 95% confidence intervals (CI) were derived to assess the significance of between-treatment differences in TOX, TWiST, REL, and Q-TWiST. A relative gain in Q-TWiST (vs mean overall survival of gemcitabine) of ≥10% and ≥15% was defined as clinically important and clearly clinically important, respectively. Results: Patients on nab-paclitaxel + gemcitabine spent a significantly longer time in every state and experienced significantly greater overall Q-TWiST (+1.7 months [95% CI = 0.8, 2.7]) than those receiving gemcitabine alone (8.2 months [95% CI = 7.5, 8.9] vs 6.5 months [95% CI = 5.8, 7.0]), assuming base-case utilities of TOX/REL = 0.50. This Q-TWiST gain ranged from 1.0 month (95% CI = 0.1, 1.9), when REL/TOX utilities were both 0, to 2.5 months (95% CI = 1.3, 3.7), when REL/TOX utilities were both 1. Relative gains in Q-TWiST were 21% in favor of nab-paclitaxel + gemcitabine in the base case, and ranged from 12–30% in sensitivity analyses. Conclusions: There are limitations to Q-TWiST analyses, e.g., imprecision when defining duration/severity of TOX and lack of prospective collection of utilities. This analysis addressed these issues via sensitivity analyses and conservative assumptions to show that nab-paclitaxel + gemcitabine results in statistically significant and clinically important gains in quality-adjusted survival, when compared to gemcitabine alone, in treatment-naive metastatic pancreatic adenocarcinoma patients.

Survival, quality-adjusted survival, and other clinical end points in older advanced non-small-cell lung cancer patients treated with albumin-bound paclitaxel

Background:This analysis compared the quality-adjusted survival and clinical outcomes of albumin-bound paclitaxel+carboplatin (nab-PC) vs solvent-based paclitaxel+carboplatin (sb-PC) as first-line therapy in advanced non-small-cell lung cancer (NSCLC) in older patients.Methods:Using age-based subgroup data from a randomised Phase-3 clinical trial, nab-PC and sb-PC were compared with respect to overall response rate (ORR), overall survival (OS), progression-free survival (PFS), quality of life (QoL), safety/toxicity, and quality-adjusted time without symptoms or toxicity (Q-TWiST) with ages ⩾60 and ⩾70 years as cut points.Results:Among patients aged ⩾60 years (N=546), nab-PC (N=265) significantly increased ORR and prolonged OS, despite a non-significant improvement in PFS, vs sb-PC (N=281). Nab-PC improved QoL and was associated with less neuropathy, arthralgia, and myalgia but resulted in more anaemia and thrombocytopenia. Nab-PC yielded significant Q-TWiST benefits (11.1 vs 9.8 months; 95% CI of gain: 0.2–2.6), with a relative Q-TWiST gain of 10.8% (ranging from 6.4% to 15.1% in threshold analysis). In the ⩾70 years age group, nab-PC showed similar, but non-significant, ORR, PFS, and Q-TWiST benefits and significantly improved OS and QoL.Conclusion:Nab-PC as first-line therapy in older patients with advanced NSCLC increased ORR, OS, and QoL and resulted in quality-adjusted survival gains compared with standard sb-PC.

Population-based economic impact of nab-paclitaxel plus gemcitabine in metastatic pancreatic cancer.

16 Background: Increasingly, assessing the quality of cancer treatment involves scrutiny of both outcomes and economics, particularly for advances in areas where generic agents have been standards of care. With nab-paclitaxel plus gemcitabine (nab-P/G) demonstrating a significantly improved updated median overall survival in first-line metastatic pancreatic cancer (1mPanc) patients (pts) vs gemcitabine (G) monotherapy (8.7 vs 6.6 months), this analysis aims to estimate the economic impact for a US health plan population, from adding nab-P/G as a treatment option for this condition. METHODS A three-year budget impact model was constructed to estimate 1mPanc costs for nab-P/G, G, gemcitabine + erlotinib (EG), other G combinations (OG), and FOLFIRINOX (F), from a US health plan perspective in 2013 US dollars. Inputs for prevalence, drug, administration, G-CSF, and adverse events were derived from SEER, prescribing information, publications, 3Q2014 Medicare reimbursement rates, and other public sources. The model used 2013 patient treatment mix rates as reported by Cartwright et al (ASCO 2013) with nab-P/G growing to 25% by 2015. RESULTS A population mirroring the US age mix would have 7 pts with 1mPanc annually per 100,000 lives. Treatment mix for 2013 was 27% F, 8% nab-P/G, 51% G, 8% EG, and 6% OG. Total costs per course of therapy per patient (pt) are shown in table. Baseline (before nab-P/G) population costs per 100,000 lives were

1261PCOMPARISON OF OUTCOMES BETWEEN RESPONDERS AND NONRESPONDERS TO FIRST-LINE PACLITAXEL/CARBOPLATIN (P/C) DOUBLET CHEMOTHERAPY IN PATIENTS (PTS) WITH ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC)

111,400 (

Cost-effectiveness of nab-paclitaxel plus gemcitabine versus erlotinib plus gemcitabine in metastatic pancreatic cancer.

15,914 per average pt). Adding nab-P/G to the treatment mix for 1mPanc added

Budget Impact of Albumin-Bound Paclitaxel + Gemcitabine in the Treatment of Metastatic Pancreatic Cancer

6,083 to population costs (

Cost Effectiveness of Nab-Paclitaxel Plus Carboplatin (nab-PC) Relative to Bevacizumab Plus Solvent-Based Paclitaxel and Carboplatin (B+sb-PC) in Elderly Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

869 per average pt) for 2013, rising to

The importance of response to chemotherapy in advanced squamous non-small cell lung cancer (NSCLC).

20,117 (

Impact of nab-paclitaxel (nab-P) plus gemcitabine (G) vs gemcitabine alone on Karnofsky performance status (KPS) in metastatic pancreatic cancer.

2,874 per average pt) for 2015 vs the baseline. CONCLUSIONS Adding nab-paclitaxel plus gemcitabine as a treatment option for first-line metastatic pancreatic cancer pts was estimated to increase costs by 12% (about

A quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis comparing nab-paclitaxel plus carboplatin (nab-PC) with solvent-based paclitaxel plus carboplatin (sb-PC) in first-line advanced non-small cell lung cancer (NSCLC).

2000 per average pt per year) over a three year period. The principal cost drivers were replacement of generic gemcitabine monotherapy, partially offset by savings from replacing FOLFIRINOX. [Table: see text].