Pemetrexed for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer

Abstract

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of pemetrexed for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), in accordance with the licensed indication, based upon the evidence submission from the manufacturer (Eli Lilly) to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The primary clinical outcome measure was progression free survival (PFS). Secondary outcomes included overall survival (OS), time to worsening of symptoms, objective tumour response rate, adverse events and changes in lung cancer symptom scale. Data for two populations were presented: patients with non-squamous NSCLC histology and patients with adenocarcinoma histology. The clinical evidence was derived from a double-blind, placebo-controlled randomised controlled trial (RCT), the JMEN trial. The trial compared the use of pemetrexed + best supportive care (BSC ) as maintenance therapy, with placebo + BSC in patients with NSCLC (n = 663) who had received four cycles of platinum-based chemotherapy (CTX) and whose disease had not progressed. In the licensed population (patients with nonsquamous histology), the trial demonstrated greater median PFS for patients treated with DOI: 10.3310/hta14suppl2/05 Pemetrexed for locally advanced or metastatic non-small cell lung cancer 34 pemetrexed than for patients in the placebo arm [4.5 vs 2.6 months; hazard ratio (HR) 0.44; 95% confidence interval (CI) 0.36 to 0.55, p < 0.00001]. Median OS was also greater for the pemetrexedtreated patients (15.5 vs 10.3 months; HR 0.70; 95% CI 0.56 to 0.88, p = 0.002). In addition, tumour response and disease control rates were statistically significantly greater for patients who received pemetrexed. Patient survival rates at 1 year and 2 years were higher in the pemetrexed arm. The incremental cost-effectiveness ratios (ICERs) estimated by the manufacturer's model were £33,732 per quality adjusted life-year (QALY) for the licensed nonsquamous population, and £39,364 per QALY for the adenocarcinoma subgroup. Both of these ICERs were above the standard NICE willingness-to-pay range (£20,000-£30,000 per QALY). The manufacturer also presented a case for pemetrexed to be considered as an end of life treatment. The ERG identified a number of problems in the economic model presented by the manufacturer; after correction, the base case ICER was re-estimated as £51,192 per QALY gained and likely to exceed NICE's willingness-to-pay thresholds. Following a revised economic analysis submitted by the manufacturer, the AC accepted that an ICER of £47,000 per QALY gained was most plausible. The AC also considered that maintenance treatment with pemetrexed fulfilled the end of life criteria.The guidance issued by NICE, on 20 June 20 2010, in TA190 as a result of the STA states that: People who have received pemetrexed in combination with cisplatin as first-line chemotherapy c...

CIMAvax EGF (EGF-P64K) vaccine for the treatment of non-small-cell lung cancer

“…Currently, 'continuation' or 'switch maintenance' for non-progressive disease after frontline therapy is the recommended alternative for patients with good performance status [13][14][15][16][17]. 'Continuation maintenance' implies that a chemotherapy or biological that was part of the initial platinum-based therapy is continued.…”

“…Alternatively, switch maintenance means that a third agent is initiated prior to Vaccine Profile evidence of disease progression after completion of platinumbased therapy [13][14][15][16][17]. Several drugs used as maintenance only improve the progression-free survival, while agents like pemetrexed or erlotinib also increase the overall survival of the non-squamous NSCLC patients [13][14][15][16][17]. Two antibodies targeting EGFR, cetuximab and necitumumab, were evaluated in Phase III studies in advanced NSCLC patients.…”

Cost-Effectiveness of Maintenance Pemetrexed in Patients with Advanced Nonsquamous-Cell Lung Cancer from the Perspective of the Swiss Health Care System

“…This is comparable to the €106,202/ QALY as found our study. A second and very similar cost- [33,35]. In the latter study, the cost of pemetrexed was £800 for a 500-mg vial, accounting for drug costs per patient of approximately £12,076.…”

“…In the latter study, the cost of pemetrexed was £800 for a 500-mg vial, accounting for drug costs per patient of approximately £12,076. Again, based on the study results of Ciuleanu et al [22], the ICER for pemetrexed compared with best supportive care in the non-squamous-cell patient population was calculated to be £39,364 per QALY gained, based on an incremental cost of £9,554 and an incremental QALY of 0.24 [33,35]. The ICER of £39,364 per QALY as estimated by the latter study corresponds to €46,449 per QALY, partially as a consequence of lower drug costs.…”

“…This estimate is believed to be the best approximation of the Swiss situation that is currently available. In a second analysis, the value for BSC cost per unit of time was reduced by a factor of 10, to illustrate the potential impact of low BSC costs as described in a health technology assessment report for the United Kingdom by Greenhalgh et al [33]. This wide range reflects a knowledge gap with respect to the cost of BSC [34].…”