Search

Introduction Pembrolizumab alone (IO-mono) or in combination with platinum-based chemotherapy (CT-IO) is first-line standard of care for advanced non-small cell lung cancer (NSCLC) patients with PD-L1 ≥ 50%. This retrospective multicentre study assessed real-world use and efficacy of both strategies. Methods Patients with advanced NSCLC PD-L1 ≥ 50% from eight hospitals who had received at least one cycle of IO-mono or CT-IO were included. Overall survival (OS) and real-word progression-free-survival were estimated using Kaplan–Meier methodology. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs, and a Cox model with inverse propensity treatment weighting was carried out. Results Among the 243 patients included, 141 (58%) received IO-mono and 102 (42%) CT-IO. Younger patients, those with symptomatic disease and brain metastases were more likely to be proposed CT-IO. With a median follow-up of 11.5 months (95% CI 10.4–13.3), median OS was not reached, but no difference was observed between groups (p = 0.51). Early deaths at 12 weeks were 11% (95% CI 4.6–16.9) and 15.2% (95% CI 9.0–20.9) in CT-IO and IO groups (p = 0.32). After adjustment for age, gender, performance status, histology, brain metastases, liver metastases and tobacco status, no statistically significant difference was found for OS between groups, neither in the multivariate adjusted model [HR 1.07 (95% CI 0.61–1.86), p = 0.8] nor in propensity adjusted analysis [HR 0.99 (95% CI 0.60–1.65), p = 0.99]. Male gender (HR 2.01, p = 0.01) and PS ≥ 2 (HR 3.28, p Conclusion Younger patients, those with symptomatic disease and brain metastases were more likely to be proposed CT-IO. However, sparing the chemotherapy in first-line does not appear to impact survival outcomes, even regarding early deaths.

UDC 517.5 In this article, we study the existence result of the unilateral problemwhere is a Leray–Lions operator defined on Sobolev–Orlicz space where and are two complementary -functions, the first and the second lower terms and satisfies only the growth condition and any sign condition is assumed and where is a measurable function.

In this paper, we show the existence of solutions for the nonlinear elliptic equations of the form { - div a ( x , u , ∇ u ) = f , u ∈ W 0 1 L ϕ ( Ω ) ∩ L ∞ ( Ω ) , \left\{ {\matrix{ { - {\rm{div}}\,a\left( {x,u,\nabla u} \right) = f,} \hfill \cr {u \in W_0^1L\varphi \left( \Omega \right) \cap {L^\infty }\left( \Omega \right),} \hfill \cr } } \right. where a ( x , s , ξ ) ⋅ ξ ≥ ϕ ¯ x - 1 ( ϕ ( x , h ( | s | ) ) ) ϕ ( x , | ξ | ) a\left( {x,s,\xi } \right) \cdot \xi \ge \bar \varphi _x^{ - 1}\left( {\varphi \left( {x,h\left( {\left| s \right|} \right)} \right)} \right)\varphi \left( {x,\left| \xi \right|} \right) and h : ℝ+→]0, 1] is a continuous decreasing function with unbounded primitive. The second term f belongs to LN (Ω) or to Lm (Ω), with m = r N r + 1 m = {{rN} \over {r + 1}} for some r > 0 and φ is a Musielak function satisfying the Δ2-condition.

We prove the existence of renormalized solutions to a class of nonlinear evolution equations, supplemented with initial and Dirichlet condition in the framework of generalized Sobolev spaces. The data are assumed merely integrable.

Background The European Society for Medical Oncology (ESMO) 2021 conference provided a high number of randomized phase III trial reports, many of which were claimed to be practice changing. Given the short time available for conference presentations, results and conclusions tend to have greatest priority with less time remaining for study background and study methodology. Purpose On behalf of the ESMO Practicing Oncologists Working Group, 11 potentially practice-changing reports were selected and screened for three main questions: (i) Did the investigators provide sufficient details with regard to Patients and Methods to make the results comprehensible? (ii) Were there any reasons to consider bias? (iii) To which extent did the results presented translate to clinical benefit? Results In 2 out of 11 trials, the study design presented differed considerably from the study design described at ClinicalTrials.gov. Allocation concealment was not carried out in 6 out of 11 trials. In none of the trials reporting progression-free survival was informative censoring considered an issue. In none of the trials reporting overall survival was desirable crossover considered an issue. Defined trial outcome measures depicted at ClinicalTrials.gov, which could boost or weaken the ESMO-Magnitude of Clinical Benefit Scale score, were often lacking in the presentation. Study success was claimed in a heterogeneous manner, which was often not clearly linked to overall clinical benefit. Conclusion ESMO conference presentations can inform the scientific community and catalyze further research but cannot replace the full papers in peer-reviewed journals, which are needed to estimate the thoroughness of the results, the overall impact on clinical benefit and the consequences for future treatment guidelines., Highlights • An oncological peer-reviewed paper is lengthy and well structured. • An oncological conference presentation is short and less structured, but its impact can be high. • ESMO 2021 conference encompassed many possibly practice-shaping phase III trial reports. • A survey of 11 selected reports to ascertain if the conclusions made were adequately underlined by the provided information.

Purpose: The purpose of this article is to evaluate the safety of two regorafenib dose-escalation approaches in refractory metastatic colorectal cancer (mCRC) patients.Patients and methods: Patients with mCRC and progression during or within 3 months following their last standard chemotherapy regimen were randomised to receive the approved dose of regorafenib of 160 mg QD (arm A) or 120 mg QD (arm B) administered as 3 weeks of treatment followed by 1 week off, or 160 mg QD 1 week on/1 week off (arm C). The primary end-point was the percentage of patients with G3/G4 treatment-related adverse events (AEs) in each arm.Results: There were 299 patients randomly assigned to arm A (n = 101), arm B (n = 99), or arm C (n = 99); 297 initiated treatments (arm A n = 100, arm B n = 98, arm C n = 99: pop-ulation for safety analyses). G3/4 treatment-related AEs occurred in 60%, 55%, and 54% of patients in arms A, B, and C, respectively. The most common G3/4 AEs were hypertension (19, 12, and 20 patients), fatigue (20, 14, and 15 patients), hypokalemia (11, 7, and 10 pa-tients), and hand-foot skin reaction (8, 7, and 3 patients). Median overall survival was 7.4 (IQR 4.0-13.7) months in arm A, 8.6 (IQR 3.8-13.4) in arm B, and 7.1 (IQR 4.4-12.4) in arm C.Conclusions: The alternative regorafenib dosing schedules were feasible and safe in patients with mCRC who had been previously treated with standard therapy. There was a higher nu-merical improvement on the most clinically relevant AEs in the intermittent dosing arm, particularly during the relevant first two cycles. Clinicaltrials.gov identifier: NCT02835924.(C) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Histological characteristics at the invasive front may reflect tumor aggressiveness; specifically, tumor budding (Bd) is an emerging prognostic biomarker in colon cancer (CC). We explored further the significance of Bd for risk stratification by evaluating survival of stage III CC patients included in the IDEA-France phase III trial.This post-hoc study was conducted on tissue slides from 1048 stage III CC patients. Bd was scored by central review by the Bd criteria of the 2016 International Tumor Budding Consensus Conference (ITBCC 2016) and classified as Bd1 (0-4 buds/0.785 mmOverall, Bd1, Bd2, and Bd3 were observed in 39%, 28%, and 33% of CC, respectively. Bd2 and Bd3 were associated with vascular (P = 0.002) and perineural invasions (P = 0.0009). The 3-year DFS and the 5-year OS rates for Bd (1 versus 2-3) were 79.4% versus 67.2% (P = 0.001) and 89.2% versus 80.8% (P = 0.001), respectively. This was confirmed after adjustment for relevant clinicopathological features for DFS [hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.12-1.77, P = 0.003] and OS (HR 1.65, 95% CI 1.22-2.22, P = 0.001). When combined with pTN stage and Immunoscore® subgroups, Bd significantly improved disease prognostication.Bd demonstrated its independent prognostic value for DFS and OS. Given these findings, Bd as per the ITBCC 2016 should be mandatory in every pathology report in stage III CC patients. Bd and Immunoscore® could play a complementary role in personalized health care in this setting.

ROS1-rearranged (ROS1+) non-small-cell lung cancer (NSCLC) is a rare lung cancer with limited treatment options. Phase I-II studies with ROS1-tyrosine kinase inhibitors (TKIs) included small numbers of patients and real-world data are lacking. We investigate the efficacy and safety of lorlatinib, a third-generation TKI targeting ALK and ROS1, in patients with ROS1+ NSCLC treated through an expanded access program.Consecutive patients with advanced ROS1+ NSCLC treated with lorlatinib between October 2015 and June 2019 were included. Data were collected from medical records. The primary endpoint was progression-free survival.Out of the 80 patients included, 47(59%) were female, 49(62%) never smokers (less than 100 cigarettes over the lifetime), and 68(85%) had stage IV NSCLC at diagnosis. Most frequent histology was adenocarcinoma (95%) and median age was 58.2 years. At the time of lorlatinib initiation, 51(64%) patients had brain metastases and 55(81%) were PS 0-1. Lorlatinib was administered as second/third/fourth/fifth+ line in 29%/28%/18%/26% of patients. All patients previously received at least one ROS1 TKI, and 55(69%) previously received chemotherapy. Median follow-up from lorlatinib initiation was 22.2 months. Median progression-free survival and overall survival from lorlatinib initiation were 7.1 months [95% confidence interval (CI) 5.0-9.9 months] and 19.6 months (95% CI 12.3-27.5 months). Median duration of treatment with lorlatinib was 7.4 months (95% CI 6.5-13.1 months). Overall response and disease control rates were 45% and 82%, respectively. The central nervous system response rate was 72%. Treatment was stopped due to toxicity in 10 patients (13%). The safety profile was consistent with previously published data.Lorlatinib is a major treatment option for advanced refractory ROS1+ NSCLC in treatment strategy.

In this work, we shall be concerned with the existence and uniqueness result to the nonlinear parabolic equations whose prototype is $$\begin{aligned} \left\{ \begin{array}{lll} \displaystyle \frac{\partial b( u)}{\partial t} -\varDelta _{M}u - \text{ div } \left( \overline{c}(x,t)\overline{M}^{-1}M\left( \frac{\alpha _{0}}{\lambda }|b(u)|\right) \right) =f &{} \text {in}&{} Q_{T},\\ \displaystyle u(x,t)=0 &{} \text {on} &{} \partial \varOmega \times (0,T),\\ b(u)(t=0)=b(u_{0}) &{} \text {in} &{} \varOmega , \end{array} \right. \end{aligned}$$ where $$ -\,\varDelta _{M}u{=}-\,\text{ div } ((1+|u|)^{2}Du\frac{\log (e+Du)}{|Du|})$$ , $$\overline{c}\in (L^{\infty }(Q_{T}))^{N}$$ and $$M(t)= t\log (e+t)$$ is an N-function. The data f and $$b(u_{0})$$ in $$L^{1}(Q_T)$$ and $$L^{1}(\varOmega )$$ .

We prove existence of entropy solutions to general class of unilateral nonlinear parabolic equation in inhomogeneous Musielak-Orlicz spaces avoiding ceorcivity restrictions on the second lower order term. Namely, we consider{u≥ψinQT,∂b(x,u)∂t-div(a(x,t,u,∇u))=f+div(g(x,t,u))∈L1(QT).$$\left\{ \matrix{ \matrix{ {u \ge \psi } \hfill & {{\rm{in}}} \hfill & {{Q_T},} \hfill \cr } \hfill \cr {{\partial b(x,u)} \over {\partial t}} - div\left( {a\left( {x,t,u,\nabla u} \right)} \right) = f + div\left( {g\left( {x,t,u} \right)} \right) \in {L^1}\left( {{Q_T}} \right). \hfill \cr} \right.$$The growths of the monotone vector fielda(x,t,u, ᐁu) and the non-coercive vector fieldg(x,t,u) are controlled by a generalized nonhomogeneousN- functionM(see (3.3)-(3.6)). The approach does not require any particular type of growth ofM(neither Δ2nor ᐁ2). The proof is based on penalization method.

We prove in this paper an existence result of entropy solutions for nonlinear parabolic equations of the form: $$\begin{aligned} \displaystyle \frac{\partial u}{\partial t}-{\text {div}}\, a(x,t,u,\nabla u)-\mathrm{div}\Phi (x,t,u)= f \quad \text {in }{Q_T=\Omega \times (0,T)}, \end{aligned}$$ where the lower order term $$\Phi $$ satisfies only a natural growth condition prescribed by the N-function M defining the Orlicz spaces framework and the data f are an element of $$L^1(Q_T)$$ . We do not assume any restriction neither on M nor on its complementary $$\overline{M}$$ . No particular growth is considered on $$\Phi $$ .

The existence result of renormalized solutions for a class of nonlinear parabolic systems with variable exponents. The main contribution of our work is the proof of the existence of renormalized solutions without the coercivity condition on nonlinearities which allows us to use the Gagliardo–Nirenberg theorem in the proof. Наведено результат iснування перенормованих розв’язкiв для класу нелiнiйних параболiчних систем з експонентою, що змiнюється.

Resume Introduction La cohorte EOLE visait a decrire en vie reelle les caracteristiques et la prise en charge de patients avec cancer bronchique non a petites cellules (CBNPC), non epidermoide, avance ou en rechute, debutant bevacizumab associe a une chimiotherapie en premiere ligne, ainsi que l’efficacite et la tolerance du bevacizumab. Methodes Au total, 423 patients ont ete inclus dans cette etude non interventionnelle, prospective et nationale, avec un recueil trimestriel des donnees pendant 18 mois. Resultats Parmi les 407 patients analyses (âge moyen 60 ± 10 ans, hommes 68 %, ECOG-PS ≤ 1 88 %, fumeurs/anciens fumeurs 87 %, comorbidites cardiovasculaires 40 %), tous sauf 2 ont recu bevacizumab (7,5 ou 15 mg/kg/3 semaines : 99 %) en association avec un doublet de chimiotherapie. 160 (60 %) patients ayant complete l’induction ont eu une maintenance par le bevacizumab. La mediane de survie sans progression etait de 6,9 mois (IC 95 % : 6,0–7,5). La mediane de survie globale (12,8 mois [IC 95 % : 10,4–14,7]) etait plus longue si ECOG-PS ≤ 1 (14,4 mois [IC 95 % : 12,3–15,9] versus 4,9 mois [IC 95 % : 3,4–8,3] si ECOG-PS = 2). Un total de 131 (32 %) patients ont presente au moins un evenement indesirable grave et 51 (12 %) au moins un evenement indesirable grave relie au bevacizumab. Conclusion EOLE confirme en vie reelle l’efficacite et la securite d’emploi du bevacizumab chez des patients avec CBNPC avance.

In this paper we will prove the existence of solutions of the unilateral problem Au - div Φ(x,u) + H(x, u, ∇ u) = μ in Musielak spaces, where A is a Leray-Lions operator defined on D(A) ⊂ W01 LM (Ω), μ ∈ L(Ω) + W-1 EM'(Ω), where M and M' are two complementary Musielak-Orlicz functions and both the first and the second lower terms Φ and H satisfies only the growth condition and u ≥ ζ where ζ is a measurable function.

Introduction Dans l’essai CM 227 partie 1, l’association NIVO + IPI a ameliore la survie globale (OS) en 1L de traitement du CBNPC avance, independamment de l’expression de PD-L1. CM 9LA ( NCT03215706 ) est une etude randomisee de phase 3 evaluant l’association NIVO + IPI + 2 cycles CT vs CT en 1L de traitement du CBNPC avance. Methodes Les adultes atteints d’un CBNPC avance, naifs de traitement, ont ete randomises dans les groupes NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + CT (2 cycles) (n = 361) ou CT seule (4 cycles) (n = 358), stratifies selon le statut PD-L1 ( Resultats Lors d’une analyse intermediaire pre-specifiee (suivi minimum : 8,1 mois), l’OS etait prolongee significativement avec NIVO + IPI + CT vs CT (HR : 0,69, IC a 96,71 %C : 0,55–0,87 ; p = 0,0006), de meme pour la PFS et l’ORR. Avec un suivi plus long (minimum 12,7 mois), l’OS restait plus importante avec NIVO + IPI + CT vs CT : mediane 15,6 vs 10,9 mois (HR : 0,66, IC a 95 % : 0,55–0,80) ; les taux d’OS a 1 an etaient de 63 % vs 47 %. Le benefice clinique etait coherent pour tous les criteres d’efficacite parmi les differents sous-groupes cles, y compris par PD-L1 et par histologie. Des evenements indesirables de grade 3–4 lies aux traitements etaient de 47 % dans le bras NIVO + IPI + CT vs 38 % dans le bras CT. Conclusion L’OS a ete amelioree de maniere statistiquement significative avec NIVO + IPI + CT vs CT (4 cycles) en 1L de traitement du CBNPC avance. Aucun nouveau signal de securite n’a ete identifie.

We give an existence result of the obstacle parabolic problem: $$\begin{aligned} \left\{ \begin{array}{ll} u\ge \psi &{}\ \ \text{ a.e. } \text{ in } \ \Omega \times (0,T)\\ \displaystyle \frac{\partial b(x,u)}{\partial t} -div(a(x,t,u,\nabla u))+div(\phi (x,t,u)) =f &{}\ \ \text{ in }\ \Omega \times (0,T) .\\ \end{array} \right. \end{aligned}$$ The main contribution of our work is to prove the existence of an entropy solution without the coercivity condition on \(\phi \). The second term f belongs to \(L^{1}(\Omega \times (0,T))\) and \(b(.,u_0)\in L^1(\Omega )\). The proof is based on the penalization methods.

Volumetric repainting is considered as one of the techniques for motion mitigation in proton therapy. Faster layer switching time to deliver a volumetric repainting proton plan is very critical to reduce the overall treatment time. Recently, IBA (proton therapy vendor at the Miami Cancer Institute) has implemented a “field regulation” – a new feature to reduce the switching time between layers by applying a magnetic field setpoint to specific groups of magnets. In order to investigate the impact of field regulation and volumetric repainting technique on the spot size, several spot maps were generated. The spot sizes were measured at the isocenter and four off-axis points using the Lynx 2D scintillation detector. The average difference in spot size between two delivery sequences (“down” vs. “up” directions) for given energy at all five locations was 0.6±0.5%. The measurement results from the current study demonstrated that the impact of field regulation on the spot size was very minimal, and this was true for both the volumetric and non-volumetric techniques on a ProteusPLUS proton system with a PBS dedicated nozzle.

IF 11.855; International audience

Background ctDNA has been recently suggested as a major prognostic factor in resected stage II and III colon cancer patients (pts)1,2. Its predictive value for adjuvant treatment intensity or duration is currently unknown. We have analyzed here ctDNA from pts enrolled in the IDEA-FRANCE trial3, its prognostic value and its predictive value for treatment duration (3 or 6 months). Methods ctDNA was tested by using the detection of 2 methylated markers (WIF1 and NPY) by digital droplet PCR accordingly to a method developed and validated for colorectal cancer 4-6. Comparisons for pts and tumour characteristics and DFS will be done between the ctDNA tested pts and the full study population and between ctDNA positive and negative pts. DFS has been analyzed in the 6 and 3M treatment arms according to ctDNA results. Subgroup analyses for high- and low-risk pts were pre-planned. Results Of the 1345/2010 pts that consented to the IDEA translational research program, with available blood sample for ctDNA testing, 805 have been sampled before chemotherapy start and fully analyzed. More PS 0 (77% vs 71%) and more T4 and/or N2 (28% vs 23%) were observed in the 805 pts studied here than in the 1205 pts left. 696 pts were found ctDNA- and 109 ctDNA + (13.5%). ctDNA+ pts were more often T4, poorly differentiated and with tumour perforation. 2-year DFS was 64% vs 82% in ctDNA+ and – pts, respectively (HR :1.75 (95%CI 1.25-2.45) p = 0.001). In multivariate analysis including Age, Gender, MSI, perforation, T stage, N stage and treatment arm, ctDNA was confirmed as an independent prognostic marker (adj.HR: 1.85 (95%CI 1.31 to 2.61) p Conclusions In this first ctDNA assessment on a large series coming from a phase III clinical trial we found 13.5% of pts with ctDNA post-surgery. ctDNA was confirmed as an independent prognostic marker. In this series, 6 months of treatment seems better in both ctDNA+ and- pts. [1]Tie J, et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer.Sci Transl Med. 2016 Jul 6;8(346):346ra92. [2]Scholer LV, et al. Clinical Implications of Monitoring Circulating Tumor DNA in Patients with Colorectal Cancer. Clin Cancer Res. 2017 Sep 15;23(18):5437-5445. [3] Andre T, et al.Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, phase III Trial.J Clin Oncol. 2018 May 20;36(15):1469-1477. [4] Garrigou S, et al. A Study of Hypermethylated Circulating Tumor DNA as a Universal Colorectal Cancer Biomarker. Clin Chem. 2016;62:1129-1139. [5] Garlan F, et al. Early Evaluation of Circulating Tumor DNA as Marker of Therapeutic Efficacy in Metastatic Colorectal Cancer Patients (PLACOL Study). Clin Cancer Res.2017;23:5416-5425. [6] Bachet JB, et al. RAS mutation analysis in circulating tumor DNA from patients with metastatic colorectal cancer: the AGEO RASANC prospective multicenter study. Ann Oncol. 2018May 1;29(5):1211-1219. Clinical trial identification NCT00958737. Legal entity responsible for the study Gercor-Prodige. Funding Clinical trial: INCa, GERCOR; Translational project: ARC (Association de Recherche contre le Cancer, Paris, France). Disclosure J. Taieb: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Servier; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: pierre fabre; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi. D. Vernerey: Honoraria (self), Advisory / Consultancy: HalioDX; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Janssen. J. Bennouna: Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim. All other authors have declared no conflicts of interest.

Background Talactoferrin alfa is an oral dendritic cell (DC)-mediated immunotherapy (DCMI). We tested whether talactoferrin was superior to placebo in advanced non-small-cell lung cancer (NSCLC). Patients and methods An FORTIS-M trial was an international, multicenter, randomized, double-blind comparison of talactoferrin (1.5g p.o. BID) versus placebo BID, in patients with stage IIIB/IV NSCLC whose disease had failed two or more prior regimens. Treatment was administered for a maximum of five 14-week cycles. The primary efficacy end point was overall survival (OS); secondary end points included 6- and 12-month survival, progression-free survival (PFS), and disease control rate (DCR). Results Seven hundred and forty-two patients were randomly assigned (2:1) to talactoferrin (497) or placebo (245). The median OS in the intent-to-treat (ITT) population was 7.66 months in the placebo arm and 7.49 months in the talactoferrin arm [hazard ratio (HR), 1.04; 95% CI, 0.873–1.24; P = 0.6602]. The 6-month survival rates were 59.9% (95% CI, 53.4% to 65.8%) and 55.7% (95% CI, 51.1% to 59.9%), respectively. The 12-month survival rates were 32.2% (95% CI, 26.3% to 38.2%) and 30.9% (95% CI, 26.8% to 35%), respectively. The median PFS rates were 1.64 months and 1.68 months, respectively (HR, 0.99; 95% CI, 0.835–1.16; P = 0.8073). The DCRs were 38.4 and 37.6%, respectively [stratified odds ratio (OR), 0.96; 95% CI, 0.698–1.33; P = 0.8336]. The safety profiles were comparable between arms. Conclusions There was no improvement in efficacy with talactoferrin alfa in patients with advanced NSCLC whose disease had failed two or more previous regimens.

The EOLE cohort aimed to describe, in routine clinical practice, the characteristics and management of patients receiving bevacizumab in combination with first-line metastatic chemotherapy for advanced metastatic or recurrent non squamous non-small cell lung cancer (nsNSCLC), as well as its efficacy and safety.A total of 423 patients were enrolled in this prospective, national, multicenter study. Data were collected every 3 months over an 18-month period.Amongst the 407 patients analyzed (mean age 60±10 years, male 68%, ECOG-PS≤1 88%, smokers or former smokers 87%, cardiovascular comorbidities 40%), all except for 2 patients received bevacizumab (7.5 or 15mg/kg/3 weeks in 99% of patients) in combination with doublet chemotherapy. A total of 160 (60%) patients who completed induction received bevacizumab maintenance therapy. Median progression-free survival was 6.9 months (95% CI=[6.0-7.5]). Median overall survival (12.8 months [10.4-14.7]) was longer in patients with ECOG-PS≤1 (14.4 months [12.3-15.9] versus 4.9 months [3.4-8.3] if ECOG-PS=2). A total of 131 (32%) patients experienced at least one serious adverse event (SAE), and 51 (12%) at least one bevacizumab-related SAE.EOLE confirms the efficacy and safety of bevacizumab in aNSCLC patients, in current medical practice.

Background: Afatinib has demonstrated clinical benefit in patients with non-small-cell lung cancer progressing after treatment with erlotinib/gefitinib. This phase III trial prospectively assessed whether continued irreversible ErbB-family blockade with afatinib plus paclitaxel has superior outcomes versus switching to chemotherapy alone in patients acquiring resistance to erlotinib/gefitinib and afatinib monotherapy. Patients and methods: Patients with relapsed/refractory disease following ≥ 1 line of chemotherapy, and whose tumors had progressed following initial disease control (≥ 12 weeks) with erlotinib/gefitinib and thereafter afatinib (50 mg/day), were randomized 2:1 to receive afatinib plus paclitaxel (40 mg/day; 80 mg/m2/week) or investigator's choice of single-agent chemotherapy. The primary end point was progression-free survival (PFS). Other end points included objective response rate (ORR), overall survival (OS), safety and patient-reported outcomes. Results: Two hundred and two patients with progressive disease following clinical benefit from afatinib were randomized to afatinib plus paclitaxel (n ≥ 134) or single-agent chemotherapy (n ≥ 68). PFS (median 5.6 versus 2.8 months, hazard ratio 0.60, P ≥ 0.003) and ORR (32.1% versus 13.2%, P ≥ 0.005) significantly improved with afatinib plus paclitaxel. There was no difference in OS. Global health status/quality of life was maintained with afatinib plus paclitaxel over the entire treatment period. The median treatment duration was 133 and 51 days with afatinib plus paclitaxel and single-agent chemotherapy, respectively; 48.5% of patients receiving afatinib plus paclitaxel and 30.0% of patients receiving single-agent chemotherapy experienced drug-related grade 3/4 adverse events. Treatment-related adverse events were consistent with those previously reported with each agent. Conclusion: Afatinib plus paclitaxel improved PFS and ORR compared with single-agent chemotherapy in patients who acquired resistance to erlotinib/gefitinib and progressed on afatinib after initial benefit. LUX-Lung 5 is the first prospective trial to demonstrate the benefit of continued ErbB targeting post-progression, versus switching to single-agent chemotherapy. Trial registration number: NCT01085136 (clinicaltrials.gov).

Au cours des 20 dernieres annees, la prise en charge des cancers colorectaux metastatiques s’est considerablement modifiee. Les avancees du traitement medical, l’elargissement des indications chirurgicales et la generalisation des decisions plurisciplinaires ont permis un allongement sensible de la survie globale (SG) passant de 14 mois en 1990 a 30 mois. Cet article presente une synthese des principales etudes recemment publiees dans la pathologie colorectale metastatique: place des therapeutiques ciblees, chronologie d’administration et strategie multiligne des traitements medicaux et chirurgicaux. La discussion aborde la problematique de la strategie optimale dans la pratiquemedicale en attendant la carte d’identite moleculaire.

Resume MAGE-A3 est l’acronyme de Melanoma Associated Antigen-A3. Cet antigene est exprime a la surface des cellules cancereuses de nombreuses tumeurs mais pas sur les cellules normales a l’exception des cellules germinales testiculaires. Il est present dans 30 a 60 % des cancers bronchiques non a petites cellules sans que sa fonction ne soit definie. Sa reconnaissance par les lymphocytes T cytotoxiques implique sa presentation a la surface cellulaire par les molecules HLA de type A1 dont les cellules germinales sont depourvues. Il est donc une cible interessante pour une immunotherapie anticancereuse. Les resultats prometteurs des premiers essais de vaccination anticancereuse avec l’antigene MAGE-A3 ont permis d’obtenir une reponse immunitaire cellulaire avec peut-etre un benefice en survie. Ils devront etre confirmes par des essais randomises de phase III actuellement en cours en situation adjuvante.

In this paper, we prove the existence and uniqueness of solutions of unilateral problems of the type − div a ( x , ∇ u ) = f in the framework of Orlicz spaces. The main contribution of our work is proving the existence of a solution without any restriction on the N -function M of the Orlicz spaces.

Actuellement, la prise en charge des CBNPC en 1re ligne de chimiotherapie est fonction de l’histologie. Le developpement des laboratoires d’anatomopathologie et de biologie moleculaire, parallelement a l’essor de nouvelles therapeutiques, est necessaire a la selection des patients selon des criteres predictifs d’efficacite et de tolerance permettant de definir un traitement sur mesure.