Intergroupe Francophone de Cancérologie Thoracique: Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial

Service de Pneumologie, Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France.
The Lancet (Impact Factor: 45.22). 08/2011; 378(9796):1079-88. DOI: 10.1016/S0140-6736(11)60780-0
Source: PubMed


Platinum-based doublet chemotherapy is recommended to treat advanced non-small-cell lung cancer (NSCLC) in fit, non-elderly adults, but monotherapy is recommended for patients older than 70 years. We compared a carboplatin and paclitaxel doublet chemotherapy regimen with monotherapy in elderly patients with advanced NSCLC.
In this multicentre, open-label, phase 3, randomised trial we recruited patients aged 70-89 years with locally advanced or metastatic NSCLC and WHO performance status scores of 0-2. Patients received either four cycles (3 weeks on treatment, 1 week off treatment) of carboplatin (on day 1) plus paclitaxel (on days 1, 8, and 15) or five cycles (2 weeks on treatment, 1 week off treatment) of vinorelbine or gemcitabine monotherapy. Randomisation was done centrally with the minimisation method. The primary endpoint was overall survival, and analysis was done by intention to treat. This trial is registered, number NCT00298415.
451 patients were enrolled. 226 were randomly assigned monotherapy and 225 doublet chemotherapy. Median age was 77 years and median follow-up was 30.3 months (range 8.6-45.2). Median overall survival was 10.3 months for doublet chemotherapy and 6.2 months for monotherapy (hazard ratio 0.64, 95% CI 0.52-0.78; p<0.0001); 1-year survival was 44.5% (95% CI 37.9-50.9) and 25.4% (19.9-31.3), respectively. Toxic effects were more frequent in the doublet chemotherapy group than in the monotherapy group (most frequent, decreased neutrophil count (108 [48.4%] vs 28 [12.4%]; asthenia 23 [10.3%] vs 13 [5.8%]).
Despite increased toxic effects, platinum-based doublet chemotherapy was associated with survival benefits compared with vinorelbine or gemcitabine monotherapy in elderly patients with NSCLC. We feel that the current treatment paradigm for these patients should be reconsidered.
Intergroupe Francophone de Cancérologie Thoracique, Institut National du Cancer.

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    • "Interestingly, when compared to standard paclitaxel, weekly paclitaxel appears to have equivalent benefit, but reduces the risk of neutropenia and peripheral neuropathy (62). The landmark trial investigating the use of platinum doublets in the elderly is Intergroupe Francophone Cancérologie Thoracique (IFCT)-0501 (63). This trial included 451 patients aged 70–89 years, with locally advanced or metastatic NSCLC and a PS of ECOG 0–2. "
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    ABSTRACT: An increasing proportion of patients with advanced non-small cell lung cancer (NSCLC) are over 70 years old, raising unique challenges for treatment decision-making. While these patients are underrepresented in clinical trials, there is an emerging body of evidence associated with this group. The lesson of comprehensive geriatric assessment is that chronological age does not always correlate with physiological age and a variety of important co-morbidities and geriatric syndromes can go undetected in a typical history and physical. These co-morbidities and expected physiologic changes due to aging complicate decision-making around appropriate treatment. This review discusses geriatric assessment in elderly cancer patients and evaluates the current evidence for chemotherapy and targeted therapy for patients with advanced NSCLC aged ≥70 years.
    Frontiers in Oncology 07/2014; 4:178. DOI:10.3389/fonc.2014.00178
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    • "Therefore, with few limitations, elderly patients with advanced nonsquamous NSCLC and good performance status should be treated similarly to younger patients. We and others have shown that platinum-based doublet therapy is a tolerable, viable option for elderly advanced NSCLC patients [11, 12, 14]. However, our conclusions are hypothesis generating, as this retrospective analysis had a small sample size and unbalanced between-arm patient characteristics. "
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    ABSTRACT: Many physicians consider platinum-doublet chemotherapy inappropriate for elderly patients, regardless of their medical fitness. This was a retrospective subgroup analysis of data from a multicenter, randomized, phase III clinical trial evaluating pemetrexed + carboplatin versus docetaxel + carboplatin in elderly chemo-naive patients with advanced, nonsquamous non-small cell lung cancer (NSCLC). Data from elderly patients (aged ≥65 years and ≥70 years) were evaluated using the same statistical methods as those used in patients aged <70 years and qualified intent-to-treat (Q-ITT) populations. The primary objective of the clinical trial was comparison of pemetrexed + carboplatin with docetaxel + carboplatin in terms of survival without grade 3 or 4 toxicity in chemo-naive NSCLC patients. The ≥65- and ≥70-year age groups had 68 and 37 patients, respectively. Among patients aged ≥65 years, the adjusted hazard ratio (HR) for survival without grade 3-4 toxicity (HR 0.40, 95 % confidence interval [CI] 0.23-0.70) favored pemetrexed + carboplatin; this was similar to the HRs in patients aged ≥70 years (HR 0.43, 95 % CI 0.20-0.92), patients aged <70 years (HR 0.44, 95 % CI 0.32-0.62), and the Q-ITT population (HR 0.45, 95 % CI 0.34-0.61). The median values for overall survival (OS) and progression-free survival (PFS) were similar across all age-group subsets and the Q-ITT population. The HRs for OS and PFS were similar for all age-group subsets, except for the ≥70-year age group, which favored pemetrexed + carboplatin to a greater extent. The toxicity profile was similar across age groups, with the exception of diarrhea, mucosal inflammation, and grade 3-4 neutropenia and leukopenia, which were slightly more common in elderly patients in both treatment arms. Between-arm differences in the toxicity profiles for the ≥65-, ≥70- and <70-year age subgroups were similar to those in the Q-ITT population. There were no on-study deaths or unexpected toxicities. The benefits of pemetrexed + carboplatin were maintained, and toxicity was manageable in both elderly subgroups. The favorable risk-benefit profile of pemetrexed + carboplatin makes it an appropriate first-line treatment option for elderly patients with advanced nonsquamous NSCLC.
    11/2013; 13(4). DOI:10.1007/s40268-013-0032-6
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    • "Despite the common practice (at the time) of treating older patients with monotherapy, only three patients (6.7 %) in our cohort received first-line monotherapy, whereas all others received platinum-doublets. Our experience was that most doublet regimen are well tolerated in the elderly, and this echoed the finding in the IFCT-0501 trial in which patients aged at least 70 years were randomized to receive either vinorelbine or gemcitabine alone or with monthly carboplatin combined with weekly paclitaxel demonstrated that there was a highly significant benefit of survival in the doublet chemotherapy arm [30]. Even in a priori unfavourable prognostic subgroups (patients with a PS score of two, those aged >80 years or those with an activities of daily living scale score of <6), doublet therapy was associated with a survival advantage over monotherapy "
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    ABSTRACT: Lung cancer remains the top cause of cancer morbidity and mortality in the world. Although the identification of epidermal growth factor receptor (EGFR) gene mutations could predict efficacy of tyrosine kinase inhibitor (TKI), testing for predictive biomarkers are not always possible due to tissue availability. The overall therapeutic decision remains a clinical one for a significant proportion of elderly patients with advanced stage lung cancer but no known EGFR mutation status. The purpose of this study was to compare the outcome of drug treatment modalities in progression-free survival (PFS) and overall survival (OS) for elderly with advanced-stage non-small cell lung cancer (NSCLC) and to identify clinical parameters that could predict treatment outcome. Clinical records of patients aged 70 years or older with advanced-stage NSCLC who have received treatment were reviewed. A group of gender- and histology-matched subjects younger than age 70 years were identified as controls. Fifty-six elderly patients were included. The median age at diagnosis was 73 years; 60.7 % received only one line of treatment. Baseline performance status (PS) was the only predictor of improved PFS (p = 0.042) and OS (p = 0.002). There was no difference in survival between the upfront chemotherapy and the TKI groups CONCLUSIONS: In elderly with advanced-stage NSCLC without known EGFR mutation status, use of EGFR-TKI and chemotherapy resulted in comparable survival benefits. Age was not predictive of worse treatment outcome. The baseline PS should be taken into consideration in the therapeutic decision in elderly with NSCLC where the EGFR mutation status is not known.
    Beiträge zur Klinik der Tuberkulose 08/2013; 191(6). DOI:10.1007/s00408-013-9498-9 · 2.27 Impact Factor
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