Roughly 20% of patients with non-small-cell lung cancer exhibit locally advanced, unresectable, stage III disease. Concurrent platinum-based chemoradiotherapy is the backbone treatment, which is ...followed by maintenance immunotherapy, yet with poor long-term prognosis. This phase II trial (IFCT-0803) sought to evaluate whether adding cetuximab to cisplatin and pemetrexed chemoradiotherapy would improve its efficacy in these patients.
Eligible patients received weekly cetuximab (loading dose 400mg/m2 day 1; subsequent weekly 250mg/m2 doses until two weeks postradiotherapy). Chemotherapy comprised cisplatin (75mg/m2) and pemetrexed (500mg/m2), both delivered on day 1 of a 21-day cycle of maximally four. Irradiation with maximally 66Gy started on day 22. Disease control rate at week 16 was the primary endpoint.
One hundred and six patients were included (99 eligible patients). Compliance exceeded 95% for day 1 of chemotherapy cycles 1 to 4, with 76% patients receiving the 12 planned cetuximab doses. Maximal grade 3 toxicity occurred in 63% patients, and maximal grade 4 in 9.6%. The primary endpoint involving the first 95 eligible patients comprised two (2.1%) complete responses, 57 (60.0%) partial responses, and 27 (28.4%) stable diseases. This 90.5% disease control rate (95% confidence interval 95% CI: 84.6%–96.4%) was achieved at week 16. After median 63.0-month follow-up, one-year and two-year survival rates were 75.8% and 59.5%. Median overall survival was 35.8months (95% CI: 23.5–NR), and median progression-free survival 14.4months (95% CI: 11.2–18.8), with one-year and two-year progression-free survival rates of 57.6% and 34.3%.
These survival rates compare favourably with published data, thus justifying further development of cetuximab-based induction chemoradiotherapy.
Environ 20 % des cancers du poumon non à petites cellules sont de stade III, localement évolués et non résécables. La chimioradiothérapie à base de platine concomitante est le traitement de référence, qui est suivi d’une immunothérapie d’entretien, mais avec un pronostic défavorable à long terme. Cet essai de phase II (IFCT-0803) visait à évaluer si l’ajout de cétuximab au cisplatine et au pémétrexed améliorerait son efficacité chez ces patients.
Les patients éligibles ont reçu du cétuximab chaque semaine (dose de charge 400mg/m2 au jour 1 ; doses hebdomadaires ultérieures de 250mg/m2 jusqu’à deux semaines après la radiothérapie). La chimiothérapie comprenait du cisplatine (75mg/m2) et du pémétrexed (500mg/m2), tous deux administrés le jour 1 d’un cycle de 21 jours de quatre au maximum. L’irradiation avec un maximum de 66Gy a commencé le jour 22. Le taux de contrôle de la maladie à la semaine 16 était le critère d’évaluation principal.
Cent six patients ont été inclus (99 patients éligibles). L’observance a dépassé 95 % pour le jour 1 des cycles de chimiothérapie 1 à 4, avec 76 % des patients recevant les 12 doses de cétuximab prévues. Une toxicité maximale de grade 3 est survenue chez 63 % des patients et une toxicité maximale de grade 4 chez 9,6 %. Le critère principal d’évaluation sur les 95 premiers patients éligibles comprenait deux réponses complètes (2,1 %), 57 réponses partielles (60,0 %) et 27 maladies stables (28,4 %). Le taux de contrôle de la maladie à la semaine 16 était de 90,5 % (intervalle de confiance à 95 % IC95 % : 84,6 % à 96,4 %). Après un suivi médian de 63 mois, les taux de survie à un an et à deux ans étaient respectivement de 75,8 % et 59,5 %. La médiane de survie globale était de 35,8 mois (IC95 % : 23,5–NR) et la survie médiane sans progression de 14,4 mois (IC95 % : 11,2–18,8), avec des taux de survie sans progression à un an et deux ans respectivement de 57,6 % et 34,3 %.
Les taux de survie dans l’étude IFCT-0803 se comparent favorablement aux données publiées, justifiant ainsi le développement ultérieur de la chimioradiothérapie d’induction à base de cétuximab.
Brain metastases are a frequent feature of the course of non-small cell lung carcinoma (NSCLC). The potential usefulness of prophylactic cranial irradiation (PCI) has led to the search for target ...groups likely to derive benefit. This multivariate analysis looked for factors predictive of brain metastases in a group of stages I–III NSCLC patients under care of the thoracic oncology unit of Besançon University Hospital from 1977 to 2001. All the patients had the same follow-up. They were divided into two groups: BM
+ when they had a brain metastasis as the first site of progression, whether solitary or not, and BM
− otherwise. Variables analysed were age, gender, performance status (0–1 versus 2–3), weight-loss stage T-status, N-status, pathological type, type of treatment, administration of chemotherapy, use of cisplatin and response to treatment. Three hundred and five patients were eligible and there were 77 patients (25.25%) in the BM
+ group. Median time to onset of brain metastases was 12 months (1–163 months) and median survival from the diagnosis of brain metastases was 6 months (1–65 months). Factors predictive of brain progression were age ≤62 years (RR: 2.5, 95% CI: 1.33–4.76 and
P=0.004), T4 tumour status (RR: 3.75, 95% CI: 1.72–8.21 and
P=0.0009), N2-3 (RR: 2.61, 95% CI: 1.32–5.15 and
P=0.0057), and adenocarcinoma (RR: 3.39, 95% CI: 1.78–6.46 and
P=0.0002). No aspect of treatment plays a role in the frequency of this type of metastasis. These factors predictive of brain progression could serve as a basis for the selection of patients with the aim of sitting of studies on prophylactic cranial irradiation in NSCLC.
The present systematic review was performed under the auspices of the European Lung Cancer Working Party (ELCWP) in order to determine the role of early intermediate criteria (surrogate markers), ...instead of survival, in determining treatment efficacy in patients with lung cancer. Initially, the level of evidence for the use of overall survival to evaluate treatment efficacy was reviewed. Nine questions were then formulated by the ELCWP. After reviewing the literature with experts on these questions, it can be concluded that overall survival is still the best criterion for predicting treatment efficacy in lung cancer. Some intermediate criteria can be early predictors, if not surrogates, for survival, despite limitations in their potential application: these include time to progression, progression-free survival, objective response, local control after radiotherapy, downstaging in locally advanced nonsmall cell lung cancer (NSCLC), complete resection and pathological TNM in resected NSCLC, and a few circulating markers. Other criteria assessed in these recommendations are not currently adequate surrogates of survival in lung cancer.
The assessment of health-related quality of life (HRQoL) has seen exponential growth in oncology clinical trials. However, the measurement of HRQoL has yet to be optimised in routine clinical ...practice. This study aimed at exploring the operationalisation of HRQoL in clinical practice with the goal of reaching a consensus from a panel of physicians.
Physicians involved in the management of lung cancer patients in France were recruited to participate in a Delphi study. The study involved three rounds of iterated queries to gain consensus on management aspects of HRQoL, including timing of discussion on HRQoL, which specific domains of HRQoL should be discussed, and what was the most appropriate method of assessment. The threshold adopted for consensus was at least 70% agreement among physicians. A scientific committee reviewed results following each round of the Delphi study.
A representative panel of 60 physicians participated in this study. Consensus was obtained for HRQoL management at all time points in the patient care pathway. Panellists agreed that HRQoL discussions should occur during routine visits and hospitalisation. The involvement of patients' relatives was also recognised as important, except when discussing side-effects and involvement of a multidisciplinary team. There was a lack of consensus on a systematic assessment for all patients at each visit and no consensus on how HRQoL should be measured in clinical practice.
HRQoL discussions are considered an integral part in the management of lung cancer patients, and are deemed key to success in patient–physician interaction. Further research is required to harmonise how best to implement HRQoL assessment.
•HRQoL was considered part of routine clinical visits in thoracic oncology by French physicians.•HRQoL was deemed key in the patient–physician interaction during the patient care pathway.•The implementation of the quality-of-life assessment is not yet in place, and the tools to assess it are not yet identified.•Further work should be conducted to harmonise how to best implement and use quality-of-life assessment in routine practice.
Several clinical and biological parameters are known to influence the efficacy of second-line erlotinib therapy for nonsmall cell lung cancer (NSCLC), but their medico-economic impact has not been ...evaluated. The objective of this study was to compare the incremental cost-effectiveness ratios of strategies for second-line erlotinib initiation in NSCLC: clinically guided initiation (nonsmoking females with adenocarcinoma received erlotinib; all other patients received docetaxel) and biologically guided selection (patients with epidermal growth factor receptor (EGFR) mutation received erlotinib; patients with wild-type EGFR or unknown status received docetaxel), compared with initiation with no patient selection (strategy reference). A Markov model was constructed. Outcomes (overall and progression-free survival), transition probabilities and direct medical costs (from the French third-party payer's perspective) were prospectively collected for individual patients treated with either erlotinib or docetaxel, from treatment initiation to disease progression. Published data were used to estimate utilities and post-progression costs. Sensitivity analyses were performed. The biologically and clinically guided strategies were both more efficient (incremental quality-adjusted life-yrs equal to 0.080 and 0.081, respectively) and less expensive (cost decrease equal to €5,020 and €5,815, respectively) than the no-selection strategy, and the biologically guided strategy was slightly less expensive than the clinically guided strategy. Sensitivity analyses confirmed the robustness of the results. The cost-effectiveness of second-line NSCLC treatment is improved when patients are selected on either clinical or biological grounds.
Although it induces a relevant reduction in the risk of both visceral metastases and locoregional recurrences, the combination of chemotherapy and surgery only marginally improves the survival of ...patients with Stage IIIA(N2) (International Union Against Cancer staging and classification system) nonsmall-cell lung carcinoma (NSCLC). The purpose of the current study was to analyze the patterns of relapse in these patients.
In this study, the authors compared the patterns of relapse in 81 patients with clinically detectable N2 NSCLC who had been treated with preoperative chemotherapy with the relapse patterns of 186 comparable patients who had been treated with primary surgery. Clinically detectable N2 (cN2) denotes mediastinal lymph node enlargement on computed tomography scan, which then is confirmed by mediastinoscopy.
Overall 20% of patients developed a locoregional recurrence. Chemotherapy decreased the risk of visceral metastasis as 28% of the patients preoperatively treated and 38%of those not treated with preoperative chemotherapy presented a visceral metastasis (P < 0.05). Preoperative chemotherapy and adenocarcinoma subtypes were associated with a higher rate of brain metastasis (P < 0.05). Thirty-two percent of the patients treated preoperatively and 18% of those not treated with preoperative chemotherapy presented a brain metastasis (P < 0.05), which was isolated in 22% and 11% of the patients, respectively (P < 0.05).
The current study found that preoperative chemotherapy for cN2 decreases the risk of visceral metastasis but is associated with a high rate of isolated brain metastases. Prophylactic cranial irradiation may need to be reinvestigated in clinical trials, especially in patients who present with an adenocarcinoma.
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