Intergroupe Francophone De Research Articles

IND227 phase III (P3) study of cisplatin/pemetrexed (CP) with or without pembrolizumab (pembro) in patients (pts) with malignant pleural mesothelioma (PM): A CCTG, NCIN, and IFCT trial.

LBA8505 Background: The vast majority of pts with PM have unresectable disease, due to co-morbidities and/or advanced stage. In unresectable PM, standard first line treatment has been C(or carboplatin)P for 20 years but it is usually only moderately efficient, mostly on epithelioid (E)PM, with a global median overall survival (mOS) around 12 months (m), an improved quality-of-life (QoL), and mild toxicity. Trial CM743 demonstrated a significant improvement in mOS for nivolumab/ipilimumab (NI) over CP (18.1 versus 14.1 m), particularly for non-EPM, but 30% NI pts experienced > grade 3 toxicity. Thus, alternative therapies to improve mOS and tolerability are needed. Methods: Canadian Cancer Trials Group (CCTG) IND 227 is an academic, open-label, randomized P3 study of the CCTG, National Cancer Institute of Naples (NCIN) and Intergroupe Francophone de Cancérologie Thoracique (IFCT). The study was supported by grants to CCTG (Canadian Cancer Society -707213); Merck & Co. Inc provided pembrolizumab (pembro) and a grant to support study conduct. Untreated unresectable PM pts ≥ 18 years with ECOG performance status 0-1, adequate hematological, renal and hepatic function, no active autoimmune disease, brain metastases, interstitial lung disease or other active co-morbidities, were randomized 1:1 to CP with or without pembro and stratified by histology (E vs. non-E). Carboplatin was allowed if C contraindicated. Radiological review (BICR) and PD-L1 testing was centralised. mOS was the primary endpoint; median progression-free survival (PFS) and response rate (RR), QoL (EORTC QLQ-C30 + QLQ-LC13) and economic analysis were secondary. Results: A total 440 PM pts were randomized; 218 to CP and 222 to CP-pembro. Data cut-off was 16 September 2022 when the required events was observed. All pts were included in the analyses. Arms were well balanced. Seven pts opted not to receive CP. Median exposure of CP was comparable between arms. Subsequent treatment with chemotherapy was similar in both arms, while 59 pts in CP arm (vs 17 CP-pembro pts) received immunotherapeutics. Using a stratified log rank test, mOS was 17.3m vs 16.1m for CP-pembro vs CP (HR 0.79 95%CI 0.64-0.98; p=0.0324), mPFS was 7.13m vs 7.16m (HR 0.80, 95%CI 0.65-0.99, p=0.0372). BOR was significantly higher for CP-pembro (63% vs 40%, p < 0.0001). Grade 3 or higher pembro related adverse events (AEs) occurred in 19% of patients (88% were grade 3; the most common were fatigue (5%) and diarrhea, pneumonitis and irAE (2% each)), and 16% of pts discontinued pembro per protocol for related AEs (most commonly diarrhea and pneumonitis). Conclusions: With a statistically significant improvement in mOS and acceptable tolerability. CP-pembro is an option for treatment naïve, unresectable PM. Clinical trial information: NCT02784171 .

Outcomes of thymic epithelial tumors (TETs) with pleural metastases: Real-world insight from RYTHMIC.

8578 Background: TETs are rare and potentially aggressive malignancies with high associated prevalence of autoimmune disorders (AIDs). The pleura is the main metastatic site at relapse, referred as Masaoka-Koga stage (MK) IVa. The benefit of surgical management is unknown, so we have collected outcomes of patients with MK IVa TETs in a large prospective database. Methods: RYTHMIC (Réseau tumeurs THYMiques et Cancer) is a French nationwide network mandated to systematically discuss every case of TETs. The database, hosted by IFCT (Intergroupe Francophone de Cancérologie Thoracique), prospectively includes all consecutive pts with a diagnosis of TET discussed in RYTHMIC national or regional tumor boards. We analyzed epidemiologic, clinical and pathological characteristics of patients (pts) with MK IVa TETs. Results: From January 2012 to December 2019, 2909 pts were included in the database, including 182 MK IVa (6.2%). The median age at diagnosis was 63.5 (range 9 to 91). 58/182 (32%) pts reported AIDs, 76% myasthenia gravis. 129/182 pts had synchronous pleural metastasis. 118/182 (65%) tumors were resected, of them 10 (8.4%) had only pericardial metastases. Thymoma (T) B2 rate was 35.6%, B3 17.8% and thymic carcinoma (TC) 13.5%. Induction chemotherapy (CT) was given in 46 (39%) T and 10 (8%) TC with response rate of 50% and 70% respectively. Thymectomy was performed in addition to pleurectomy in 44 pts (37.2%), pericardiectomy in 68 (57.6%), lung resection in 80 (67.8%) or pneumonectomy in 15 (12.7%). Node resection was performed in 57.6% (n = 67), 12 (18%) were positive. The complete resection rate assessed by surgeons was 57% with a median of 15 (0 to 28) resected pleural metastasis. Intrapleural chemotherapy was added for 19 (16%) pts. No mortality was reported 90 days after surgery procedure. Median follow-up was 36 months. Pleural recurrence was seen in 47 (72%) pts. Median disease-free survival (DFS) was 39 vs 16 months in resected vs not resected tumors (p < 0.0001), 5-years overall survival (OS) was 88 vs 66% (p = 0.28), respectively. Risk of relapse decreased by 60% with surgery (HR = 0.4, 95CI (0.25-0.62); p < 0.0001). Conclusions: The prevalence of MK IVa in our cohort was 6.2%. Surgery appears to be a safe and valid option for pts with MK IVa TET at diagnosis.

Prevalence of autoimmune diseases in thymic epithelial tumors (TET) insights from RYTHMIC.

9073 Background: TET are associated with autoimmune disorders (AID) in up to 30% of patients (pts). However, there have been wide variations in the reported prevalence of AID in TET pts in small single-center series. RYTHMIC (Réseau tumeurs THYMiques et Cancer) is a French network mandated to systematically discuss every case of TET. We aimed to describe the prevalence of AID in a large French population. Methods: RYTHMIC database, hosted by IFCT (Intergroupe Francophone de Cancérologie Thoracique), prospectively includes all consecutive pts with a diagnosis of TET discussed in French national or regional tumor boards. We analyzed epidemiologic, clinical and pathological characteristics of pts with TET’s related AID. Results: From January 2012 to December 2019, 2909 pts were included in the database. The mean age at diagnosis of TET was 54 and 52% were male. In the overall population, Masaoka Koga stages were well balanced with 12.6% (n = 187) stage I, 8.8% (n = 131) stage IIa, 8.4% (n = 124) stage IIb, 11.1% (n = 164) stage III and 8.5% (n = 125) stage IV. There were 364 (12.5%) events of AID in 302 pts. 62 pts (17%) had more than 1 AID. Among the events, 236 were myasthenia gravis (MG) (64.8%), 19 Hypo-gammaglobulinemia syndrome (5.2%), 15 pure red cell aplasia (4.1%), 18 thyroiditis (4.9%) and 16 systemic erythematous lupus (4.4%). Diagnosis of AID was mostly done at tumor diagnosis (n = 239, 65.7%) but some patient had AID diagnosed before diagnosis (n = 67, 18.4%) or during follow up (n = 32, 8.8%). Among pts presenting AID, B2 was the most common subtype (n = 133, 36.5%). The incidence of AID per subtype was as follow: A (n = 10/81, 12.3%), AB (n = 48/225, 21.3%), B1 (n = 35/130, 26.9%), B2 (n = 133/295, 45.0%), B3 (n = 46/113, 40.7%), thymic carcinoma (n = 16/275, 5.8%). Conclusions: The prevalence of AID in pts with TET was 12.5%, > 40% in B2 and B3 subtypes. Diagnosis of AID can be delayed compared to the diagnosis of TET. Immunotherapy indication should be carefully assessed in pts with TET other than thymic carcinoma.

Role of the YAP-1 Transcriptional Target cIAP2 in the Differential Susceptibility to Chemotherapy of Non-Small-Cell Lung Cancer (NSCLC) Patients with Tumor RASSF1A Gene Methylation from the Phase 3 IFCT-0002 Trial.

RASSF1 gene methylation predicts longer disease-free survival (DFS) and overall survival (OS) in patients with early-stage non-small-cell lung cancer treated using paclitaxel-based neo-adjuvant chemotherapy compared to patients receiving a gemcitabine-based regimen, according to the randomized Phase 3 IFCT (Intergroupe Francophone de Cancérologie Thoracique)-0002 trial. To better understand these results, this study used four human bronchial epithelial cell (HBEC) models (HBEC-3, HBEC-3-RasV12, A549, and H1299) and modulated the expression of RASSF1A or YAP-1. Wound-healing, invasion, proliferation and apoptosis assays were then carried out and the expression of YAP-1 transcriptional targets was quantified using a quantitative polymerase chain reaction. This study reports herein that gemcitabine synergizes with RASSF1A, silencing to increase the IAP-2 expression, which in turn not only interferes with cell proliferation but also promotes cell migration. This contributes to the aggressive behavior of RASSF1A-depleted cells, as confirmed by a combined knockdown of IAP-2 and RASSF1A. Conversely, paclitaxel does not increase the IAP-2 expression but limits the invasiveness of RASSF1A-depleted cells, presumably by rescuing microtubule stabilization. Overall, these data provide a functional insight that supports the prognostic value of RASSF1 gene methylation on survival of early-stage lung cancer patients receiving perioperative paclitaxel-based treatment compared to gemcitabine-based treatment, identifying IAP-2 as a novel biomarker indicative of YAP-1-mediated modulation of chemo-sensitivity in lung cancer.

FDA Approval Summary: Dabrafenib and Trametinib for the Treatment of Metastatic Non-Small Cell Lung Cancers Harboring BRAF V600E Mutations.

The approvals of dabrafenib and trametinib, administered concurrently, provide a new regimen for the treatment of a rare subset of non-small cell lung cancer (NSCLC) and demonstrate how drugs active for treatment of BRAF-mutant tumors in one setting predict efficacy and can provide supportive evidence for approval in another setting. The FDA also approved the first next-generation sequencing oncology panel test for simultaneous assessment of multiple actionable mutations, which will facilitate selection of optimal, personalized therapy. The test was shown to accurately and reliably select patients with NSCLC with the BRAF V600E mutation for whom treatment with dabrafenib and trametinib is the optimal treatment.

Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial

Malignant pleural mesothelioma is an aggressive cancer with poor prognosis, linked to occupational asbestos exposure. Vascular endothelial growth factor is a key mitogen for malignant pleural mesothelioma cells, therefore targeting of vascular endothelial growth factor might prove effective. We aimed to assess the effect on survival of bevacizumab when added to the present standard of care, cisplatin plus pemetrexed, as first-line treatment of advanced malignant pleural mesothelioma. In this randomised, controlled, open-label, phase 3 trial, we recruited patients aged 18-75 years with unresectable malignant pleural mesothelioma who had not received previous chemotherapy, had an Eastern Cooperative Oncology Group performance status of 0-2, had no substantial cardiovascular comorbidity, were not amenable to curative surgery, had at least one evaluable (pleural effusion) or measurable (pleural tumour solid thickening) lesion with CT, and a life expectancy of >12 weeks from 73 hospitals in France. Exclusion criteria were presence of central nervous system metastases, use of antiaggregant treatments (aspirin ≥325 mg per day, clopidogrel, ticlopidine, or dipyridamole), anti-vitamin K drugs at a curative dose, treatment with low-molecular-weight heparin at a curative dose, and treatment with non-steroidal anti-inflammatory drugs. We randomly allocated patients (1:1; minimisation method used [random factor of 0·8]; patients stratified by histology [epithelioid vs sarcomatoid or mixed histology subtypes], performance status score [0-1 vs 2], study centre, or smoking status [never smokers vs smokers]) to receive intravenously 500 mg/m(2) pemetrexed plus 75 mg/m(2) cisplatin with (PCB) or without (PC) 15 mg/kg bevacizumab in 21 day cycles for up to six cycles, until progression or toxic effects. The primary outcome was overall survival (OS) in the intention-to treat population. Treatment was open label. This IFCT-GFPC-0701 trial is registered with ClinicalTrials.gov, number NCT00651456. From Feb 13, 2008, to Jan 5, 2014, we randomly assigned 448 patients to treatment (223 [50%] to PCB and 225 [50%] to PC). OS was significantly longer with PCB (median 18·8 months [95% CI 15·9-22·6]) than with PC (16·1 months [14·0-17·9]; hazard ratio 0·77 [0·62-0·95]; p=0·0167). Overall, 158 (71%) of 222 patients given PCB and 139 (62%) of 224 patients given PC had grade 3-4 adverse events. We noted more grade 3 or higher hypertension (51 [23%] of 222 vs 0) and thrombotic events (13 [6%] of 222 vs 2 [1%] of 224) with PCB than with PC. Addition of bevacizumab to pemetrexed plus cisplatin significantly improved OS in malignant pleural mesothelioma at the cost of expected manageable toxic effects, therefore it should be considered as a suitable treatment for the disease. Intergroupe Francophone de Cancérologie Thoracique (IFCT).

Prognostic value of health-related quality of life for overall survival in elderly non-small-cell lung cancer patients

BackgroundWe investigated whether the health-related quality of life (HRQoL) score is a prognostic factor for overall survival (OS) in elderly patients with advanced non-small-cell lung cancer (NSCLC). MethodsWe included 451 NSCLC patients aged 70–89 years enrolled in the Intergroupe Francophone de Cancérologie Thoracique 0501 trial, using scores of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 at baseline to investigate the prognostic value of HRQoL for OS, in addition to conventional factors. Cox regression model was used for both univariate and multivariate analyses of OS. ResultsGlobal health status (GH) dimension score at baseline was associated with favourable OS when adjusted for clinical, functional, and histological factors (hazard ratio [HR]: 0.986; 95% confidence interval [CI]: 0.980–0.992).We distinguished three groups according to GH score: high (GH <46), intermediate (46 ≤GH ≤67), and low (GH >67) mortality risk. The median OS values were 14.5, 8.2, and 5.3 months in the low-, intermediate-, and high-risk categories, respectively (log-rank P <0.0001).In the high-risk group, doublet chemotherapy was not associated with favourable OS (HR: 0.70; 95% CI: 0.49–1.003; P=0.052), whereas in the intermediate- and low-risk groups, doublet chemotherapy was associated with favourable OS (HR: 0.72; 95% CI: 0.54–0.96; P=0.023 and HR: 0.50; 95% CI: 0.30–0.84; P=0.0089, respectively). ConclusionThis study supports the additional prognostic value of HRQoL data at diagnosis to identify vulnerable subpopulations in elderly NSCLC patients. HRQoL could thus be valuable in selecting patients who will benefit from doublet chemotherapy.

Chemotherapy Effectiveness After First-Line Gefitinib Treatment for Advanced Lepidic Predominant Adenocarcinoma (Formerly Advanced Bronchioloalveolar Carcinoma): Exploratory Analysis of the IFCT-0401 Trial

This study explored whether chemotherapy after first-line gefitinib was effective in patients with advanced lepidic predominant adenocarcinoma (LPA), formerly advanced bronchioloalveolar carcinoma, who were enrolled in the Intergroupe Francophone de Cancérologie Thoracique (IFCT)-0401 trial. Overall, 88 patients presenting advanced LPA were enrolled in the IFCT-0401 trial, receiving gefitinib as first-line therapy. No predefined second-line treatment was mandatory in the case of progression or limiting toxicity under gefitinib. However, the carboplatin plus paclitaxel regimen was recommended for patients with a performance status (PS) 0 or 1 and gemcitabine monotherapy for those with a PS 2. For these patients, data concerning treatment efficacy was collected from the IFCT-0401 trial database. In total, 47 patients (53%) received second-line treatment after the failure of gefitinib, with 43 having PS 0 or 1. Regarding treatment, 43 were treated with chemotherapy, with 38 receiving a platinum-doublet regimen (taxane-based, n = 29; gemcitabine-based, n = 9) and five receiving monotherapy (gemcitabine, n = 3; pemetrexed, n = 2). The overall response rate (ORR) to chemotherapy was 21% (95% confidence interval [CI]: 10-36), disease control rate 56% (95% CI: 40-71), and median progression-free survival (PFS) 3.0 months (95% CI: 2.4-4.9). For patients receiving a platinum doublet (n = 38), ORR was 21% (95% CI: 10-37), with disease control rate being 55% (95% CI: 38-71), and median PFS 2.9 months (95% CI: 2.4-4.4). For patients receiving taxane-based regimen (n = 29) and gemcitabine-based regimen (n = 12), ORR was 28% and 0%, respectively, with a median PFS of 3.3 and 2.0 months, respectively, (p = 0.0243). The two patients receiving pemetrexed experienced a prolonged response. Multivariate Cox model analysis revealed that only the use of taxane-based chemotherapy or pemetrexed was related to PFS. Platinum-doublet chemotherapy showed some effectiveness in treating advanced LPA patients after first-line gefitinib. Our findings also suggest that taxane-based chemotherapy and pemetrexed should be investigated further in future clinical trials.

Prognostic value of pathologic complete response to preoperative chemotherapy in early-stage non small cell lung cancer: Combined analysis of two IFCT randomized trials.

7057 Background: Our study aimed to evaluate whether pathologic complete response (pCR) in early-stage non-small cell lung cancer (NSCLC) following neoadjuvant chemotherapy resulted in improved outcome and to determine predictive factors for pCR. Methods: Eligible patients with stage IB or II NSCLC were included in two consecutive Intergroupe Francophone de Cancérologie Thoracique (IFCT) phase III trials evaluating platinum-based neoadjuvant chemotherapy, with pCR defined by the absence of viable cancer cells in the resected surgical specimen. Results: Among the 492 patients analyzed, 41 (8.3%) achieved pCR. In the pCR group, 5-year overall survival (OS) was 80.0% compared to 55.8% in the non-pCR group (p=0.0007). In multivariate analyses, pCR was a favorable prognostic factor of OS (RR=0.34; 95% CI=0.18-0.64) in addition to squamous cell carcinoma (SCC), weight loss ≤5%, and stage IB disease. Five-year disease-free survival (DFS) was 80.1% in the pCR group compared to 44.8% in the non-pCR group (p&lt;0.0001). Two patients (4.9%) in the pCR group experienced disease recurrence compared to 193 patients (42.8%) in the non-pCR group. SCC subtype was the only independent predictor of pCR (OR=4.30; 95% CI=1.90-9.72). Conclusions: Our results showed that pCR after preoperative chemotherapy was a favorable prognostic factor in Stage IB-II NSCLC. Our study is the largest published series evaluating pCRs following preoperative chemotherapy. The only factor predictive of pCR was SCC. Identifying molecular predictive markers for pCR may help in distinguishing patients likely to benefit from neoadjuvant chemotherapy and in choosing the most adequate preoperative chemotherapy regimen.

Pathologic Complete Response to Preoperative Chemotherapy Predicts Cure in Early-Stage Non–Small-Cell Lung Cancer: Combined Analysis of Two IFCT Randomized Trials

Our study aimed to evaluate whether pathologic complete response (pCR) in early-stage non-small-cell lung cancer (NSCLC) after neoadjuvant chemotherapy resulted in improved outcome, and to determine predictive factors for pCR. Eligible patients with stage-IB or -II NSCLC were included in two consecutive Intergroupe Francophone de Cancérologie Thoracique phase-III trials evaluating platinum-based neoadjuvant chemotherapy, with pCR defined by the absence of viable cancer cells in the resected surgical specimen. Among the 492 patients analyzed, 41 (8.3%) achieved pCR. In the pCR group, 5-year overall survival was 80.0% compared with 55.8% in the non-pCR group (p = 0.0007). In multivariate analyses, pCR was a favorable prognostic factor of overall survival (relative risk = 0.34; 95% confidence interval = 0.18-0.64) in addition to squamous-cell carcinoma, weight loss less than or equal to 5%, and stage-IB disease. Five-year disease-free survival was 80.1% in the pCR group compared to 44.8% in the non-pCR group (p < 0.0001). Two patients (4.9%) in the pCR group experienced disease recurrence compared to 193 patients (42.8%) in the non-pCR group. SCC subtype was the only independent predictor of pCR (odds ratio [OR] = 4.30; 95% confidence interval = 1.90-9.72). Our results showed that pCR after preoperative chemotherapy was a favorable prognostic factor in stage-IB-II NSCLC. Our study is the largest published series evaluating pCRs after preoperative chemotherapy. The only factor predictive of pCR was squamous-cell carcinoma. Identifying molecular predictive markers for pCR may help in distinguishing patients likely to benefit from neoadjuvant chemotherapy and in choosing the most adequate preoperative chemotherapy regimen.

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

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.

Chemotherapy for advanced non-small-cell lung cancer patients with poor performance

Evaluation of: Morère JF, Bréchot JM, Westeel V et al. Randomized Phase II trial of gefitinib or gemcitabine or docetaxel chemotherapy in patients with advanced non-small-cell lung cancer and a performance status of 2 or 3 (IFCT-0301 study). Lung Cancer DOI: 10.1016/j.lungcan.2010.03.003 (2010) (Epub ahead of print).Previous studies have recommended single-agent chemotherapy as an important alternative for non-small-cell lung cancer (NSCLC) patients with old age or poor performance. The authors of the evaluated article have evaluated three treatment strategies within the Intergroupe Francophone de Cancérologie Thoracique (IFCT-0301 study) as a Phase II trial. All strategies started with single-agent chemotherapy in chemotherapy-naive NSCLC patients with performance status (PS) 2 or 3. The three agents used for initial therapy in this study were gefitinib, gemcitabine and docetaxel. All three agents showed similar median progression-free survival values. Docetaxel was associated with higher response rates but also higher rates of adverse events. In subgroup analysis, patients with PS 3 did not benefit from monotherapy. This study suggests that monotherapy is still an option for NSCLC patients with PS 2; but, the study was not powered to favor one agent out of the three. In addition, because the study population did not undergo EGF receptor mutation analysis, it may not reflect the therapeutic impact of EGF receptor inhibitors, which can be tolerable in patients of poor performance.

IFCT-0401 Trial: A Phase II Study of Gefitinib Administered as First-Line Treatment in Advanced Adenocarcinoma with Bronchioloalveolar Carcinoma Subtype

Intergroupe Francophone de Cancérologie Thoracique-0401 phase II trial aimed to evaluate the efficacy and safety of gefitinib as a first-line treatment for patients with adenocarcinoma with bronchioloalveolar carcinoma subtype (ADC-BAC). Chemotherapy-naive patients (n = 88) with advanced ADC-BAC were treated with 250 mg/d of gefitinib. The primary objective was assessment of disease control rate (DCR [objective response + stable disease]) at 3 months using World Health Organization criteria. A disease control rate of 25% or greater would be of interest in this patient population. Progression-free survival (PFS), overall survival (OS), and toxicity were the secondary criteria. Clinical and disease characteristics that conferred a favorable prognosis under gefitinib were also analyzed. Disease control was achieved in 25 patients (29.4%); 11 patients (12.9%) had partial response and 14 (16.4%) had stable disease. Median PFS was 2.9 months (95% confidence interval [CI], 2.3-3.2) and median OS was 13.2 months (95% CI, 10.2-17.3). Never smokers, patients with low respiratory symptoms score, occurrence of cutaneous rash, and nonmucinous ADC-BAC subtype were associated with increased probability of disease control. Nonmucinous ADC-BAC was associated with increased PFS and OS at 3 years. Patients with nonmucinous BAC had longer OS and PFS compared with patients with other ADC-BAC variants; median PFS for nonmucinous BAC was 11.3 months (95% CI, 3.2-14.7), whereas it was 2.6 months (95% CI, 2.1-3) for mucinous BAC. As expected, toxicity was low, with dermatological problems, diarrhea, and nausea being the most common adverse events. Results from the Intergroupe Francophone de Cancérologie Thoracique-0401 trial demonstrate that gefitinib combines efficacy with low toxicity and is, therefore, suitable as a first-line treatment of advanced ADC-BAC, particularly in patients with nonmucinous BAC subtype.

Protocole IFCT-0302 : essai randomisé de deux schémas de surveillance dans les cancers bronchiques non à petites cellules complètement réséqués

The authorities advocate a minimalist attitude towards the follow-up of resected bronchial carcinoma (clinical examination and chest x-ray). A survey showed that 70% of French respiratory physicians have chosen to use the CT scanner and often endoscopy. The published data are equivocal and are often based on retrospective studies. Lung cancer is a good model for a study of post-operative surveillance. Recurrences often occur in easily observed areas, they may be detected while still asymptomatic and are sometimes potentially curable. Second primary tumours may develop at the same site. The Intergroupe Francophone de Cancerologie Thoracique (IFCT) has initiated a trial comparing simple follow-up (clinical examination, chest x-ray) with a more intensive follow-up (CT scan, fibreoptic bronchoscopy). The surveillance will take place every 6 months for 2 years and then annually until 5 years. The main aim is to determine whether intensive follow-up improves patient survival. The opposite question is equally important. If an expensive and demanding follow-up does not affect the chances of cure these results will influence our practice.

Gemcitabine induction chemotherapy in non–small cell lung cancer

Surgery has long been considered standard treatment in early stage non–small cell lung cancer. Preoperative chemotherapy is a real challenge in the treatment of these stages. Some conclusions can be drawn from the first phase II studies in stage IIIA tumors. Response rates were higher than those observed in stage IV tumors, reaching approximately 70%. Although toxicity seemed acceptable, increased morbidity and mortality have to be taken into account for the choice of preoperative regimens. Two randomized studies that included only a few patients were conducted in stage IIIA disease and showed highly positive survival results. The French randomized study argued in favor of preoperative chemotherapy with an absolute difference in survival rates that remains constant beyond the third year. New studies are ongoing to evaluate the role of the gemcitabine/cisplatin combination. Several phase II studies of this regimen in the preoperative setting or in combination with radiotherapy have been presented at the most recent meetings of the American Society of Clinical Oncology. These studies confirmed both its efficacy and good tolerability. In several ongoing randomized studies, this combination has been chosen to test the concept of preoperative chemotherapy. One such study, which compares two different strategies of preoperative chemotherapy, is by the Intergroupe Francophone de Cancérologie Thoracique. Semin Oncol 29 (suppl 9):55-60. Copyright 2002, Elsevier Science (USA). All rights reserved.

Overview of the role of neoadjuvant chemotherapy for early stage non-small cell lung cancer

Preoperative chemotherapy has been intensively studied in stage IIIA non-small cell lung cancer and, to a lesser extent, in stage IIIB. For a considerable time period, early stage non-small cell lung cancer was dropped from studies. For early investigators, shrinking the tumor size, thus allowing complete resection of initially unresectable tumors, appeared as important as destroying micrometastases. Nevertheless, analysis of relapse patterns shows that preoperative chemotherapy appears to act more on micrometastases than on local control. The first randomized studies of preoperative chemotherapy were conducted only among patients with stage IIIA disease. The French Cooperative Oncology Group presented a large randomized study among 373 stage IB, II, and IIIA patients at the American Society of Clinical Oncology meeting in May 1999. A Cox multivariate analysis showed a protective effect of preoperative chemotherapy, and this effect seemed to preferentially involve patients with early stage disease. Ongoing studies of most US and European oncology groups are including early stage tumors, as in the Southwest Oncology Group trial 9901. The new Inter-groupe Francophone de Cancérologie Thoracique also is ready to start a preoperative randomized chemotherapy study in stage I and II non-small cell lung cancer, that will compare two different strategies of preoperative chemotherapy in responding patients. Patients will be randomized to two groups: one group will receive chemotherapy before surgery and the other group will receive it before and after surgery.