Enrolment of older adults with advanced or metastatic non-small cell lung cancer in first-line clinical trials in the multicentre ESME cohort.

INTRODUCTION: There is a great need for data based on clinical trials for the older population in order to improve treatment. Historically, the inclusion rate of older adults in clinical trials has been low, but the rate specific to lung cancer is unknown, as are the factors associated with enrolment. MATERIALS AND METHODS: We used the national Epidemio-Strategy and Medical Economics Advanced or Metastatic Lung Cancer (AMLC) Data Platform, a multicentre real-life database. Inclusion criteria were patients with advanced or metastatic non-small cell lung cancer (AMNSCLC) aged 70 years or older, with at least one line of systemic treatment from 01 January 2015 to 31 December 2018. The primary objective was to evaluate the proportion of older adults enrolled in clinical trials. Secondary objectives were to identify factors associated with enrolment in clinical trials for older patients and to compare the overall survival of older adults included in trials versus those not included. RESULTS: There were 3488 patients aged ≥70 years (median age at AMNSCLC 75 years). Among older patients, 234 (6.7%) were enrolled in a clinical trial in the first-line setting. Significant factors associated with enrolment in the multivariable analysis in older patients were: good Eastern Cooperative Oncology Group (ECOG) Performance Status (PS 0) (p < 0.001), de novo versus recurrent presentation at diagnosis (p < 0.001), and non-central nervous system (CNS) metastases versus advanced setting or CNS metastases (p < 0.001). Medical history was associated with fewer inclusions (odds ratio [OR] = 0.74, 95% confidence interval [CI] [0.56; 0.99]). Among older patients, being enrolled in a trial in the first-line setting was not associated with better overall survival (OS) (hazard ratio [HR] = 1.03; 95%CI 0.86-1.22) in the multivariable analysis. DISCUSSION: In this large database, few older AMNSCLC patients were enrolled in a trial. Factors associated with enrolment were: good ECOG PS, absence of medical history, de novo AMNSCLC, and presentation with non-CNS metastases.

Impact of immune checkpoint inhibitors on the management of locally advanced or metastatic non-small cell lung cancer in real-life practice in patients initiating treatment between 2015 and 2018 in France and Germany.

OBJECTIVES: To describe the impact of immune checkpoint inhibitors (ICIs) on treatment patterns and survival outcomes in patients with locally advanced or metastatic non-small cell lung cancer (aNSCLC) in France and Germany. MATERIALS AND METHODS: Patients with aNSCLC without known ALK or EGFR mutations receiving first-line (1L) therapy were included from (i) the retrospective Epidemiological-Strategy and Medical Economics Advanced and Metastatic Lung Cancer cohort (ESME-AMLC, France; 2015-2018) and (ii) the prospective Clinical Research platform Into molecular testing, treatment and outcome of non-Small cell lung carcinoma Patients platform (CRISP, Germany; 2016-2018). Analyses were stratified according to histology. Survival outcomes were estimated using Kaplan-Meier methodology and stratified by year of 1L therapy. Data sources were analysed separately. RESULTS: In ESME-AMLC and CRISP, 8,046 and 2,359 patients were included in the study, respectively. In both countries, approximately 20 % of all patients received pembrolizumab monotherapy as 1L treatment in 2018. In ESME-AMLC, the proportion receiving an ICI over the course of treatment (any line) increased from 42.2 % (2015) to 56.1 % (2018) in patients with squamous histology, and 28.9 % to 51.9 % with non-squamous/other; in CRISP, it increased from 50.6 % (2016) to 65.2 % (2018) with squamous histology, and 40.8 % to 62.7 % with non-squamous/other. Two-year overall survival from 1L initiation was 36.8 % and 25.6 % in the squamous cohorts and 36.5 % and 30.8 % in the non-squamous/other cohorts in ESME-AMLC and CRISP, respectively. No significant change in overall survival was observed over time; however, the follow-up time available was limited in the later years of the analysis. CONCLUSION: The results of this joint research from two large clinical databases in France and Germany demonstrate the growing use of ICIs in the management of aNSCLC. Future analyses will allow for the evaluation of the impact of ICIs on long-term survival of patients with aNSCLC.

Assessment of Treatment Effects and Long-term Benefits in Immune Checkpoint Inhibitor Trials Using the Flexible Parametric Cure Model: A Systematic Review.

Importance: Compared with standard cytotoxic therapies, randomized immune checkpoint inhibitor (ICI) phase 3 trials reveal delayed benefits in terms of patient survival and/or long-term response. Such outcomes generally violate the assumption of proportional hazards, and the classical Cox proportional hazards regression model is therefore unsuitable for these types of analyses. Objective: To evaluate the ability of the flexible parametric cure model (FPCM) to estimate treatment effects and long-term responder fractions (LRFs) independently of prespecified time points. Evidence Review: This systematic review used reconstructed individual patient data from ICI advanced or metastatic melanoma and lung cancer phase 3 trials extracted from the literature. Trials published between January 1, 2010, and October 1, 2019, with long-term follow-up periods (maximum follow-up, ≥36 months in first line and ≥30 months otherwise) were selected to identify LRFs. Individual patient data for progression-free survival were reconstructed from the published randomized ICI phase 3 trial results. The FPCM was applied to estimate treatment effects on the overall population and on the following components of the population: LRF and progression-free survival in non-long-term responders. Results obtained were compared with treatment effects estimated using the Cox proportional hazards regression model. Findings: In this systematic review, among the 23 comparisons studied using the FPCM, a statistically significant association between the time-to-event component and experimental treatment was observed in the main analyses and confirmed in the sensitivity analyses of 18 comparisons. Results were discordant for 4 comparisons that were not significant by the Cox proportional hazards regression model. The LRFs varied from 1.5% to 12.7% for the control arms and from 4.6% to 38.8% for the experimental arms. Differences in LRFs varied from 2% to 29% and were significantly increased in the experimental compared with the control arms, except for 4 comparisons. Conclusions and Relevance: This systematic review of reconstructed individual patient data found that the FPCM was a complementary approach that provided a comprehensive and pertinent evaluation of benefit and risk by assessing whether ICI treatment was associated with an increased probability of patients being long-term responders or with an improved progression-free survival in patients who were not long-term responders.

Treatment strategies for unresectable locally advanced non-small cell lung cancer in the real-life ESME cohort.

BACKGROUND: Cisplatin-based chemotherapy administered concurrently to thoracic radiation therapy is the recommended treatment for fit patients with unresectable stage III NSCLC. The aim of this study was to describe patient profiles and clinical outcomes for the different treatment strategies in a real-word setting. METHODS: The epidemio-strategy and medical economics (ESME) database for advanced and metastatic lung cancer is a French, national, multicenter, observational cohort. Out of 8514 Patients, 822 patients with unresectable locally advanced NSCLC in 2015-016 were selected (mean age, 65.3 years; male gender, 69%; performance status 0-1, 77%; smokers or former smokers, 89%). RESULTS: Treatment was initiated for 736 (90%) of patients (concurrent chemoradiotherapy, n = 283; sequential chemoradiotherapy, n = 121; chemotherapy alone, n = 194; radiotherapy alone, n = 121; targeted therapy alone, n = 8; other, n = 9). Compared to the other treatment strategy groups, patients with radiotherapy alone appeared the most fragile (e.g. higher age, lower body weight or higher frequency of chronic obstructive pulmonary disease). OS rates at 12 and 24 months were 79.5% (95% CI, 73.4-84.3) and 55.3% (95% CI, 44.9-64.5) for concurrent chemoradiotherapy, and 64.3% (95% CI, 52.8-73.8) and 53.2 (95% CI, 33.2-69.6) for sequential chemoradiotherapy. CONCLUSIONS: Real-world evidence shows that concurrent chemoradiotherapy is administered to the most fit patients with non resectable locally-advanced NSCLC. Clinical outcomes are actually higher than those reported in landmark clinical trials, which suggests that an optimized and individualized selection of patients allows for prolonged survival. Long-term outcomes are similar after sequential or concurrent chemoradiotherapy.

A Real-World Study of Patients with Advanced Non-squamous Non-small Cell Lung Cancer with EGFR Exon 20 Insertion: Clinical Characteristics and Outcomes.

BACKGROUND: In Europe, few data regarding the characteristics of EGFR exon 20 insertion (20ins) mutations in non-small cell lung cancer (NSCLC) are available. OBJECTIVE: Using a large real-world cohort, we assessed the incidence, characteristics, and outcomes of patients with non-squamous (nsq) NSCLC harboring EGFR exon 20ins. PATIENTS AND METHODS: The Epidemio-Strategy and Medical Economics advanced and metastatic lung cancer data platform including advanced/metastatic nsqNSCLC patients from January 2015 was analyzed (cut-off date: June 30, 2020). Characteristics, epidermal growth factor receptor (EGFR) mutation and other mutations, treatment patterns, and clinical outcomes were assessed for patients harboring EGFR exon 20ins, common EGFR mutations, other EGFR mutations, and wild-type EGFR. Survival parameters were estimated by the Kaplan-Meier method in these four groups. RESULTS: Out of 9435 nsqNSCLC patients tested for EGFR, 1549 (16.4%) had a mutation, including 61 with EGFR exon 20ins (3.9% of all mutated EGFR). These 61 patients had a mean age of 63.6 years, were mostly female (68.9%) and non-smokers (55.7%), with de novo stage IV disease (73.8%) and performance status 0-1 (76.9%). Almost all patients (95.1%) with exon 20ins received systemic therapy (median, three lines). First-line systemic treatments consisted mainly of combination chemotherapy (70.7%), single-agent EGFR tyrosine kinase inhibitors (10.3%), and single-agent immunotherapy (5.2%). After a median follow-up of 25.0 (95% confidence interval [CI] 22.3-32.4) months, the median real-world overall survival was 24.3 (19.1-32.6) months in patients with exon 20ins compared to 35.4 (95% CI 32.6-37.5) in patients with common EGFR mutation (n = 1049) (p = 0.049) and 19.6 (95% CI 18.6-20.5) in patients with wild-type EGFR (n = 7866) (p = 0.2). CONCLUSIONS: This large national study in nsqNSCLC patients confirms that EGFR exon 20ins is a rare condition (0.6%). The prognosis associated with exon 20ins appears to be in line with that of wild-type EGFR, but worse than common EGFR mutations, highlighting the need for advancements for this rare population.

Healthcare resource utilization in advanced non-small-cell lung cancer: post hoc analysis of the randomized phase 3 REVEL study.

PURPOSE: In REVEL, patients with advanced non-small-cell lung cancer (aNSCLC) and patients with increased tumor aggressiveness (rapid disease progression (RDP), platinum-refractory disease (PRD), and high symptom burden (HSB)) benefited from second-line treatment with ramucirumab plus docetaxel over placebo plus docetaxel. This post hoc analysis describes healthcare resource utilization (HCRU) associated with the treatment. METHODS: aNSCLC patients who had progressed during or after first-line platinum-based chemotherapy were randomized to receive docetaxel and either ramucirumab or placebo until disease progression, unacceptable toxicity, withdrawal, or death. HCRU included hospitalizations, transfusions, and concomitant medications. Categorical variables (counts and percentages) were compared using Fisher's exact test. Continuous variables (mean, standard deviation (SD), median, minimum, and maximum) were compared using the Wilcoxon rank sum test. RESULTS: Patient characteristics were largely similar between treatment arms. Within the intent-to-treat (ITT) population (n = 1253), the mean treatment duration was 19.7 and 16.9 weeks in the ramucirumab and control arms, respectively; 51.0% versus 54.9% of patients received subsequent anticancer therapy, respectively. Hospitalization rates were 41.9% versus 42.6% (p = 0.863), mean length of hospital stay was 14.5 days versus 11.3 days (p = 0.066), transfusion rates were 9.9% versus 12.3% (p = 0.206), and use of granulocyte colony-stimulating factors was 41.8% versus 36.6% (p = 0.063), respectively. No significant difference was observed in HCRU between treatment arms in both ITT population and in aggressive disease subgroups including RDP (n = 209), PRD (n = 360), and HSB (n = 497). CONCLUSION: In REVEL, the addition of ramucirumab to docetaxel did not increase HCRU among patients with aggressive aNSCLC disease. These results may help inform economic evaluation of treatment for patients with aNSCLC.

Cost-effectiveness of atezolizumab versus docetaxel and nivolumab in the treatment of non-small cell lung cancer as a second line in France.

Aim: To estimate the cost-effectiveness of atezolizumab compared with docetaxel and nivolumab for the treatment of advanced non-small cell lung cancer (NSCLC), as a second-line treatment, in a French setting.Materials and methods: A three-state partitioned-survival model was developed (progression-free survival, post-progression survival, death) based on the phase IIIOAK trial on a 10-year time horizon. The comparison between nivolumab and atezolizumab came from a network meta-analysis. Utilities were estimated from the OAK trial EQ-5D applying the French utility tariffs. Overall survival (OS), progression-free survival (PFS), and treatment duration were estimated using parametric models selected using Akaike and Bayesian information criterion. Extrapolation beyond the trial duration followed NICE DSU TSD 14. Economic perspective was the one of all payers, discount rate fixed at 4% on benefits and costs. This analysis was aligned with French Haute Autorité de Santé recommendations. Results were expressed in total cost (2019) and €/QALY (Quality Adjusted Life Year). Model robustness was checked through sensitivity analyses, and a probabilistic sensitivity analysis was conducted.Results: In comparison to docetaxel, atezolizumab costs 49,429€ more and increased life expectancy by 8 months, generating 0.47 QALY. Incremental cost-effectiveness ratio was estimated at 104,835€/QALY. When comparing nivolumab to atezolizumab, a cost minimization analysis was conducted since no clear evidence supporting a difference in terms of survival benefit was reported. Using list price, and the Market Access Authorization regimens, atezolizumab saved approximately 6,000€, 9.5% of its total costs. Sensitivity analyses confirmed the robustness of our findings.Conclusion: Atezolizumab is more efficient and more costly than docetaxel in the second-line treatment of NSCLC of stage IIIB or IV, in France, with results consistent to previous French authorities' evaluation of immunotherapies in similar indication. Lastly, atezolizumab is a cost saving alternative to nivolumab, based on list price.

Systematic Screening for Occupational Exposures in Lung Cancer Patients: A Prospective French Cohort.

Occupational lung cancers are under-reported and under-compensated worldwide. We assessed systematic screening for occupational exposure to carcinogens combining a self-administered questionnaire and an occupational consultation to improve the detection of occupational lung cancers and their compensation. Social deprivation and the costs of this investigation were estimated. Patients with lung cancer received a self-administered questionnaire to collect their job history, potential exposure to carcinogens and deprivation. A physician assessed the questionnaire and recommended an occupational consultation if necessary. During the consultation, a physician assessed if the lung cancer was work-related and, if it was, delivered a medical certificate to claim for compensation. Over 18 months, 440 patients received the self-administered questionnaire: 234 returned a completed questionnaire and a consultation was required for 120 patients. Compensation was judged possible for 41 patients. Among the 35 medical certificates delivered, 19 patients received compensation. Nearly half the patients (46%) were assessed as socially deprived and these patients took significantly longer to return the questionnaire compared with those who were not deprived. The mean cost of the process was €62.65 per patient. Our results showed a systematic self-administered questionnaire can be used to identify patients potentially exposed to carcinogens and to improve compensation.

Cost-Effectiveness Analysis of Afatinib versus Gefitinib for First-Line Treatment of Advanced EGFR-Mutated Advanced Non-Small Cell Lung Cancers.

INTRODUCTION: The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib were compared in the multicenter, international, randomized, head-to-head phase 2b LUX-Lung 7 trial for first-line treatment of advanced EGFR mutation-positive NSCLCs. Afatinib and gefitinib costs and patients' outcomes in France were assessed. METHODS: A partitioned survival model was designed to assess the cost-effectiveness of afatinib versus gefitinib for EGFR mutation-positive NSCLCs. Outcomes and safety were taken primarily from the LUX-Lung 7 trial. Resource use and utilities were derived from that trial, an expert-panel questionnaire, and published literature, limiting expenditures to direct costs. Incremental cost-effectiveness ratios (ICERs) were calculated over a 10-year time horizon for the entire population, and EGFR exon 19 deletion or exon 21 L858R mutation (L858R) subgroups. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: For all EGFR mutation-positive NSCLCs, the afatinib-versus-gefitinib ICER of was €45,211 per quality-adjusted life-year (QALY) (0.170 QALY gain for an incremental cost of €7697). ICERs for EGFR exon 19 deletion and L858R populations were €38,970 and €52,518, respectively. Afatinib had 100% probability to be cost-effective at a willingness-to-pay threshold of €70,000/QALY for patients with common EGFR mutations. CONCLUSION: First-line afatinib appears cost-effective compared with gefitinib for patients with EGFR mutation-positive NSCLCs.

[Assessment of a self-administered questionnaire identifying occupational exposures among lung cancer patients]. / Évaluation d'un auto-questionnaire de repérage des expositions professionnelles chez les patients atteints de cancer bronchopulmonaire.

Ten to 29% of lung cancers might be linked to occupational factors but 60% of them are not compensated. The PROPOUMON project aimed to improve the identification, recognition and compensation of occupational lung cancer as occupational disease using a self-administered questionnaire (AQREP). One objective was to assess the AQREP, comparing it with the questionnaire drawn up by the French Language Pneumology Society (Q-SPLF). From March 2014 to September 2015, 90 lung cancer patients treated at the Centre Léon-Bérard responded to the AQREP and Q-SPLF. The two physicians in charge of the consultation assessed independently whether or not a consultation was indicated. A certificate for the compensation process was proposed when a suspicion of high or average imputability was identified. Analysis of the questionnaires was concordant for 73% of the patients. The AQREP has a sensitivity of 72% and a specificity of 73%. Its positive and negative predictive values were 62 and 82%. The information provided by 24 patients were discordant between questionnaires. In two patients with discordant evaluation (AQREP+/Q-SPLF-; AQREP-/Q-SPLF+), one Initial Medical Certificate (IMC) was written. This study made it possible to conclude that AQREP is relevant for the identification of potentially occupational lung cancers. Collegial discussion of complex cases might be considered. The project is currently been extended to other centers and to lymphoma.

Use of a Comprehensive Geriatric Assessment for the Management of Elderly Patients With Advanced Non-Small-Cell Lung Cancer: The Phase III Randomized ESOGIA-GFPC-GECP 08-02 Study.

PURPOSE: Comprehensive geriatric assessment (CGA) is recommended to assess the vulnerability of elderly patients, but its integration in cancer treatment decision making has never been prospectively evaluated. Here, in elderly patients with advanced non-small-cell lung cancer (NSCLC), we compared a standard strategy of chemotherapy allocation on the basis of performance status (PS) and age with an experimental strategy on the basis of CGA. PATIENTS AND METHODS: In a multicenter, open-label, phase III trial, elderly patients ≥ 70 years old with a PS of 0 to 2 and stage IV NSCLC were randomly assigned between chemotherapy allocation on the basis of PS and age (standard arm: carboplatin-based doublet if PS ≤ 1 and age ≤ 75 years; docetaxel if PS = 2 or age > 75 years) and treatment allocation on the basis of CGA (CGA arm: carboplatin-based doublet for fit patients, docetaxel for vulnerable patients, and best supportive care for frail patients). The primary end point was treatment failure free survival (TFFS). Secondary end points were overall survival (OS), progression-free survival, tolerability, and quality of life. RESULTS: Four hundred ninety-four patients were randomly assigned (standard arm, n = 251; CGA arm, n = 243). Median age was 77 years. In the standard and CGA arms, 35.1% and 45.7% of patients received a carboplatin-based doublet, 64.9% and 31.3% received docetaxel, and 0% and 23.0% received best supportive care, respectively. In the standard and CGA arms, median TFFS times were 3.2 and 3.1 months, respectively (hazard ratio, 0.91; 95% CI, 0.76 to 1.1), and median OS times were 6.4 and 6.1 months, respectively (hazard ratio, 0.92; 95% CI, 0.79 to 1.1). Patients in the CGA arm, compared with standard arm patients, experienced significantly less all grade toxicity (85.6% v 93.4%, respectively P = .015) and fewer treatment failures as a result of toxicity (4.8% v 11.8%, respectively; P = .007). CONCLUSION: In elderly patients with advanced NSCLC, treatment allocation on the basis of CGA failed to improve the TFFS or OS but slightly reduced treatment toxicity.

Cost-utility analysis of maintenance therapy with gemcitabine or erlotinib vs observation with predefined second-line treatment after cisplatin-gemcitabine induction chemotherapy for advanced NSCLC: IFCT-GFPC 0502-Eco phase III study.

BACKGROUND: The IFCT-GFPC 0502 phase III study reported prolongation of progression-free survival with gemcitabine or erlotinib maintenance vs. observation after cisplatin-gemcitabine induction chemotherapy for advanced non-small-cell lung cancer (NSCLC). This analysis was undertaken to assess the incremental cost-effectiveness ratio (ICER) of these strategies for the global population and pre-specified subgroups. METHODS: A cost-utility analysis evaluated the ICER of gemcitabine or erlotinib maintenance therapy vs. observation, from randomization until the end of follow-up. Direct medical costs (including drugs, hospitalization, follow-up examinations, second-line treatments and palliative care) were prospectively collected per patient during the trial, until death, from the primary health-insurance provider's perspective. Utility data were extracted from literature. Sensitivity analyses were conducted. RESULTS: The ICERs for gemcitabine or erlotinib maintenance therapy were respectively 76,625 and 184,733 euros per quality-adjusted life year (QALY). Gemcitabine continuation maintenance therapy had a favourable ICER in patients with PS = 0 (52,213 €/QALY), in responders to induction chemotherapy (64,296 €/QALY), regardless of histology (adenocarcinoma, 62,292 €/QALY, non adenocarcinoma, 83,291 €/QALY). Erlotinib maintenance showed a favourable ICER in patients with PS = 0 (94,908 €/QALY), in patients with adenocarcinoma (97,160 €/QALY) and in patient with objective response to induction (101,186 €/QALY), but it is not cost-effective in patients with PS =1, in patients with non-adenocarcinoma or with stable disease after induction chemotherapy. CONCLUSION: Gemcitabine- or erlotinib-maintenance therapy had ICERs that varied as a function of histology, PS and response to first-line chemotherapy.

[Identification of occupational exposures among patients with lung cancer]. / Repérage des expositions professionnelles chez les patients atteints de cancers bronchopulmonaires.

Despite the rising number of lung cancers recognized as occupational disease, occupational lung cancers are still under-reported. To improve the recognition of occupational lung cancer, we implemented at the Léon-Bérard Cancer Centre, a questionnaire-based process to identify occupational exposures in these patients and improve compensation. Between January 2010 and December 2011, 91 lung cancer patients responded to a questionnaire. An "occupational cancer" consultation was proposed to patients reporting exposure to carcinogens or jobs with risk of exposure. Fifty-one patients were seen in consultation (34 following the questionnaire and 17 directly addressed by the oncologist). A suspicion of high or average imputability was identified in 31 (60.8%) patients and a compensation process seemed possible for 27 (61.4%). Asbestos was the most common carcinogen identified. Among 17 compensation processes engaged, 12 succeeded and one is ongoing. The complexity of the administrative process seems to be an obstacle for patients and perpetuates inequality. The implementation of our approach increased the identification and the compensation of occupational lung cancer. Our approach responds to the objectives of the National Cancer Plan and helps to improve the overall care of patients with cancer. This approach has been awarded by the national label in 2011 "Year of the patients and their rights".

Economic impact of gefitinib for refractory non-small-cell lung cancer: a Markov model-based analysis.

UNLABELLED: Few data are available on the economics of target therapy or refractory non-small-cell lung cancer (NSCLC). OBJECTIVE: To determine the mean global management costs (MC) per patient treated with gefitinib for NSCLC, and the costs of the different management phases. METHOD: A Markov approach was used to model treatment costs in a cohort of 106 patients treated with gefitinib as part of a compassionate-use program (third-line treatment) in six public-sector teaching hospitals. The economic analysis adopted the health care payer's perspective, and only direct costs were taken into account. RESULTS: The mean duration of gefitinib treatment was 4.6 +/- 5.8 months (1-29 months); median survival was 4 months, 1-year and 2-year survival rates were 12.3% and 4.7%, respectively. The mean total management cost was 39,979 euros +/- 20,279. The model showed that first- and second-line treatments accounted for respectively 29.5% and 44.1% of this cost, while gefitinib periods represented 10.7%, periods of remission 1.25%, and terminal care 14.5%. A sensitivity analysis showed that the price of gefitinib had little influence on the total cost. CONCLUSION: The cost of third-line gefitinib therapy for NSCLC appears acceptable from the healthcare payer's perspective, but this needs to be confirmed in dedicated cost-effectiveness studies.

Paclitaxel hypersensitivity reactions: assessment of the utility of a test-dose program.

UNLABELLED: Several studies have suggested the usefulness of a test dose of paclitaxel to reduce the incidence of hypersensitivity reactions and the resulting cost of drug wastage. The aim of this study was to assess the utility of implementing such a test dose. METHOD: We retrospectively reviewed the medical charts of patients who had received one or two courses of single-agent paclitaxel or a combination chemotherapy regimen to calculate hypersensitivity reaction incidence and the cost of drug wastage. Thereafter, a paclitaxel test-dose program was routinely implemented during the first and second cycles of paclitaxel treatment for all patients. Hypersensitivity reaction incidence and drug wastage cost were again assessed. RESULTS: Before the routine use of a test dose, 162 patients received one or two paclitaxel infusions alone or in combination therapy from January 1, 1997 to February 28, 2003. Ten (6.2%) patients experienced a hypersensitivity reaction; one of them was severe. After implementation of the test-dose program, 130 patients received 244 test doses (12 mg paclitaxel/10 mL normal saline) with an intensified premedication regimen at the first and second cycles of chemotherapy from June 28, 2003 to March 2, 2005. Three patients (2.3%) experienced a minor hypersensitivity reaction, one immediately after the test dose and two during infusion of the full dose despite a well-tolerated test dose. Thus, the negative predictive value of the test dose was 98.4%. The overall incidence of hypersensitivity reactions experienced during the first or second cycle of paclitaxel chemotherapy decreased about 63% compared with the incidence before implementation of the test dose (P < 0.20). The test-dose program resulted in a 29% increase in the cost of chemotherapy (approximately 6100 dollars for 130 patients). CONCLUSION: To our knowledge, this is the largest study ever reported to test the potential cost-saving benefit of the implementation of a paclitaxel test-dose program to prevent hypersensitivity reactions. The results suggest that the routine use of a test dose is not a cost-effective measure.