Lung cancer remains a leading cause of cancer-related mortality, with heterogeneous outcomes, underscoring the need for robust prognostic biomarkers. Circulating tumor DNA (ctDNA) enables detection of actionable mutations and may provide prognostic information; however, many patients lack detectable alterations, limiting its utility for molecular-based risk stratification. We analyzed plasma from 617 treatment-naïve patients using targeted next-generation sequencing for ctDNA and immunoassays to quantify circulating H3K27Me3-nucleosomes. Survival analyses included 514 patients with ≥8-month follow-up. Elevated H3K27Me3-nucleosome levels were independently associated with poorer overall survival. Patients with levels <56 ng/mL had significantly longer survival than those with higher concentrations (26 vs 12 months; p<0.0001), including in ctDNA-negative patients (29 vs 12 months; p<0.0001). A multivariable Cox model integrating H3K27Me3, stage, mutation, and age showed good performance (C-index 0.80) and was validated in an independent cohort. Circulating H3K27Me3-nucleosomes enable clinically relevant risk stratification at diagnosis, supporting more precise patient management in lung cancer.

Background Improved lung cancer survival has led to an increase in situations requiring intensive care unit (ICU) admission. Establishing appropriate criteria for ICU admission and withholding/withdrawing life-sustaining treatment for these patients remains challenging. Methods A national multicentre prospective survey was conducted in France from August to November 2023. Participants responded to fictitious clinical cases representing three patients with metastatic lung cancer, either small cell lung cancer (SCLC) or non-SCLC (NSCLC), in a total of nine clinical situations (three each). We aimed to investigate the medical decision-making process for care intensity and explore associations with physician characteristics, patient disease status, and emergency situations. Results Overall, 305 physicians participated in this survey, primarily from oncology (33%) and intensive care (56%) departments. In case of febrile aplasia, ICU admission was proposed by 88%, 81%, and 64% of respondents for NSCLC in first line, NSCLC in second line, and SCLC in first line, respectively. Conversely, in case of tumour obstruction, only 44%, 32%, and 23% of physicians proposed ICU, respectively. The three main variables used in the decision-making process were performance status (63%), complication reversibility (61%), and anticancer treatment efficacy (40%). The suggestions of oncologists and intensivists appeared often similar, contrary to those of emergency physicians. Conclusion This survey reported similar care intensity provided by oncologists and intensivists. ICU admission was more often proposed in case of expected reversibility of organ failure. This highlights the importance of multidisciplinary discussion, standardised protocols, and training in critically ill cancer patient care.

Background:Oligoprogression (OP) is common in patients with metastatic non-small cell lung cancer (mNSCLC) treated with immune checkpoint inhibitors (ICIs). This study aims to assess the benefit and the safety profile of ablative radiotherapy (RT) for OP in mNSCLC treated with pembrolizumab in first-line setting. Methods:We retrospectively analyzed records of all consecutive mNSCLC patients who underwent treatment with pembrolizumab (+/- chemotherapy) in first-line setting and developed an OP treated with ablative RT while continuing pembrolizumab, in a French Hospital from 2019 to 2022. Primary endpoint was time to next systemic treatment (TTNT). Secondary endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety profile. Furthermore, we investigated features associated with clinical outcomes. Results:Thirty-six patients were included and 47 OPs were reported (27 patients experienced one OP, 7 two OP, and 2 three OP). The median TTNT (mTTNT) after the first OP was 19.6 months [95% confidence interval (CI): 12.4-not reached (NR)]. The median PFS (mPFS) after the first OP was 12 months (95% CI: 6.1-NR) and 10.4 months (95% CI: 3.9-NR) after the second or third OP. The median OS (mOS) from the first OP and from pembrolizumab initiation were NR. In multivariable analysis, the presence of adrenal gland was associated with shorter TTNT and OS, while OP involving bone metastasis was associated with shorter PFS. The ORR of the lesions treated with RT was 70.2%. No RT-induced severe adverse event was reported. Three patients experienced severe pembrolizumab-induced adverse events. Conclusions:In this study, RT alongside the maintenance of pembrolizumab for patients experiencing OP during first-line pembrolizumab-based therapy for mNSCLC demonstrated an acceptable safety profile and favorable outcomes. Data from phase 3 randomized trials are needed to clearly establish the benefits of this strategy in treating oligoprogressive mNSCLC.

Purpose. The growing choice of oral anticancer medications (OAMs) delivered in pharmacies puts the patients at the center of their own therapeutic management. Patient satisfaction regarding their pharmaceutical management is particularly important for adherence to their treatment. The aim of this study was to assess the satisfaction of patients treated with OAMs regarding their dispensing in community pharmacies. Methods. A cross-sectional study was conducted with a self-questionnaire proposed to patients in hospital centers and community pharmacies. The patient’s satisfaction regarding pharmacy dispensing was assessed with a visual analogue scale. Answers to questions about the quality of information they received from health professionals were recorded. The patient’s adherence to their medication was assessed with the 8-item Morisky Medication Adherence Scale (MMAS-8). Symptoms and quality of life were recorded with the QLQ-C30 questionnaire. Results. Ninety-one patients were included in the analysis. The median score of satisfaction was 89 (interquartile range: 68, 100), and 49.5% had a satisfaction score ≥90/100. Satisfaction scores were higher for patients reporting information from pharmacists for the method of administration, the management of adverse effects, and drug interactions than for patients reporting no information from pharmacists. Patient satisfaction was not related to MMAS-8 scores, symptoms, or quality of life. Multivariate analysis of patient satisfaction revealed a positive relationship with information on the administration method provided by pharmacists. Conclusions. The level of information provided on OAMs to patients should be the same between pharmacists and oncologists. Good medication dispensing practices by the pharmacist are important components of patient care and satisfaction. We encourage pharmacists to provide more medication information to their patients.

Introduction > The prognosis of metastatic non-small cell lung cancer (NSCLC) has been improved by the use of immune checkpoint inhibitors (ICI). Unfortunately, in some cases, cancer cells will develop resistance mechanisms. In case of progression in a limited number of lesions (oligoprogression), focal treatment with radiotherapy is proposed while continuing the ICI therapy.Methods > A cohort of 37 patients with metastatic NSCLC treated with nivolumab (anti-PD-1) in second or subsequent line and who received focal radiotherapy for oligoprogression with continuation of nivolumab was compared with a control cohort of 87 patients no oligoprogressor treated par immunotherapy.Results > After a median follow-up of 37 months [18; 62], the median progression free survival (PFS) in the radiotherapy-treated cohort was 15.04 versus 5.04 months in the control cohort, with a statistically significant difference (P = 0.048). The median PFS following focal radiotherapy in the oligoprogressor group was 7.5 months. In univariate analysis, the presence of lung metastasis was associated with increased PFS, in contrast to the presence of brain metastases, which were associated with decreased PFS in the radiotherapy group. The median overall survival was not reached in both groups, with no significant difference between the two cohorts.Conclusion > The combination of focal radiotherapy in case of oligoprogression and continued treatment with nivolumab in the treatment of metastatic NSCLC in the second or subsequent line of treatment seems to be with an increase in PFS.

8583 Background: Small cell lung cancer (SCLC) is a highly aggressive type of lung cancer with a tendency towards early recurrence and limited survival. Standard-of-care in 1 st -line treatment is platinum-etoposide chemotherapy plus anti-PD-L1 immune checkpoint inhibitor atezolizumab or durvalumab, based on landmark, randomized, phase 3 clinical trials. Methods: IFCT 1905-CLINATEZO is a nationwide, non-interventional, retrospective chart review study of patients (pts) with extensive-stage SCLC who received atezolizumab + chemotherapy as part of the French early access program between May 2019 and January 2020 (1402 pts). Inclusions were exhaustive per participating centers (65/307). Data collection run from February to November 2021. Key objectives were to assess effectiveness and safety of atezolizumab + chemotherapy and analyze subsequent treatment sequences. Results: The population analyzed included 518 out of the 1402 pts. There were 66% male and mean age was 65.7 years (range: 36.7-88.0); 89% had a performance status (PS) 0/1 and 27% brain metastases. Almost all the pts (96%) were smokers, with a median number of pack-years of 40. Fifty-five pts (10.6%) received at least 1 previous treatment. Median number of atezolizumab injections was 7 (range: [1-48] ) for a median duration of 4.9 months (95% CI 4.5-5.1). Twenty-seven pts (5%) were under ongoing treatment at date of last news. Atezolizumab was continued beyond disease progression in 122 pts (24%) for a median duration of 1.9 months (95% CI 1.4-2.3). Best objective response was complete and partial response in 19 (3.9%) and 378 pts (77.1%) respectively; stable disease was observed in 50 pts (10.2%). After a median follow-up of 30.8 months (95% CI: [29.9-31.5]), median overall survival (OS), 12- and 24-months OS rates were 11.3 months (95% CI: [10.1-12.4]), 46.7% (95% CI 42.3-50.9) and 21.2% (95% CI 17.7-24.8) respectively. Median real world-progression free survival (based on date of the first source evidence for progression referenced by the treating physician), 6- and 12-months rates were 5.2 months (95% CI 5.0-5.4), 37.5% (95% CI 33.3-41.7) and 15.2% (95% CI 12.2-18.6) respectively. For the pts with PS 0/1, median OS was 12.2 months (95% CI 11.0-13.5). For the 55 pts with previous treatment, median OS was 14.9 months (95% CI 10.1-21.5). A total of 326 (66.4%) pts received subsequent treatment. Conclusions: IFCT 1905-CLINATEZO study shows the reproducibility, in a real-life setting, of the key survival outcomes of IMpower-133, that may be attributed to the selection of pts fit for this regimen, the adoption of pragmatic approaches for the management of pts receiving atezolizumab, that includes concurrent radiotherapy and treatment beyond progression, and the high proportion of pts treated with 2 nd -line therapies, mostly based on chemotherapy.

Le pronostic des cancers bronchiques non à petites cellules (CBNPC) métastatiques a été amélioré par l'apport des inhibiteurs de checkpoints immunitaires. Malheureusement, dans un certain nombre de cas, les cellules cancéreuses vont développer des mécanismes de résistance. En cas de progression sur un nombre limité de lésions (oligoprogression), un traitement focal par radiothérapie peut être proposé en poursuivant le traitement par inhibiteurs de checkpoints immunitaires. Une cohorte de 37 patients atteints de CBNPC métastatiques traités par nivolumab (anti-PD-1) en deuxième ligne ou ligne ultérieure et ayant reçu une radiothérapie focale pour le traitement d'une oligoprogression avec poursuite du nivolumab a été comparée à une cohorte contrôle de 87 patients non oligoprogresseur traités par immunothérapie. Après un suivi médian de 37 mois [18 ; 62], la survie sans progression médiane dans la cohorte de patients traités par radiothérapie était de 15,04 mois contre 5,04 mois dans la cohorte contrôle, avec une différence statistiquement significative (p = 0,048). La survie sans progression médiane à la suite de radiothérapie focale dans la cohorte de patients traités par radiothérapie était de 7,5 mois. En analyse univariée, la présence de métastases pulmonaires était associée à une augmentation de la survie sans progression, à l'inverse de la présence de métastases cérébrales, qui elle était associée à une diminution de la survie sans progression dans le groupe de patients traités par radiothérapie. La survie globale médiane n'était pas atteinte dans les deux groupes, sans différence significative entre les deux cohortes. L'association de la radiothérapie focale en cas d'oligoprogression et poursuite du traitement par nivolumab dans le cadre du traitement des CBNPC métastatiques en deuxième ligne ou ligne ultérieure semble être associée à une augmentation de la survie sans progression. The prognosis of metastatic non-small cell lung cancer (NSCLC) has been improved by the use of immune checkpoint inhibitors (ICI). Unfortunately, in some cases, cancer cells will develop resistance mechanisms. In case of progression in a limited number of lesions (oligoprogression), focal treatment with radiotherapy is proposed while continuing the ICI therapy. A cohort of 37 patients with metastatic NSCLC treated with nivolumab (anti-PD-1) in second or subsequent line and who received focal radiotherapy for oligoprogression with continuation of nivolumab was compared with a control cohort of 87 patients no oligoprogressor treated par immunotherapy. After a median follow-up of 37 months [18; 62], the median progression free survival (PFS) in the radiotherapy-treated cohort was 15.04 versus 5.04 months in the control cohort, with a statistically significant difference (P = 0.048). The median PFS following focal radiotherapy in the oligoprogressor group was 7.5 months. In univariate analysis, the presence of lung metastasis was associated with increased PFS, in contrast to the presence of brain metastases, which were associated with decreased PFS in the radiotherapy group. The median overall survival was not reached in both groups, with no significant difference between the two cohorts. The combination of focal radiotherapy in case of oligoprogression and continued treatment with nivolumab in the treatment of metastatic NSCLC in the second or subsequent line of treatment seems to be with an increase in PFS.

Background: Anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC) represents a rare subset of lung cancer, with specific presentation, and multiple treatment options, including selective tyrosine kinase inhibitors (TKIs). Real world evidence is insufficient regarding the actual real-life treatment sequences in the late line setting, and available clinical trials may not reflect real-world situation. Here, we took advantage of the French Expanded Access Program (EAP) of lorlatinib, a third-generation TKI targeting ALK and ROS1, to assess treatment sequencing, and lorlatinib efficacy and safety, in patients with ALK+ NSCLC. Methods: All consecutive patients with advanced ALK+ NSCLC treated between October 2015 and June 2019 with lorlatinib as part of EAP were included. Data were collected and reviewed from medical records by independent research staff of the French Thoracic Cancer Intergroup. The primary endpoint was progression-free survival (PFS). Results: Of the 208 patients included, 117 (56%) were female, 142 (69%) were never smokers, and 180 (87%) had stage IV NSCLC at diagnosis. The most frequent histology was adenocarcinoma (94%), and the median age was 60.9 years. At the time of lorlatinib initiation, 160 (77%) patients had brain metastases, and 125 (72%) were performance status 0/1. Lorlatinib was delivered as 2nd/3rd/4th/5th + line in 4 %/17%/30%/49% of patients. A total of 162 (78%) patients had previously been treated with chemotherapy, 194 (93%) with a first -generation ALK-TKI, 195 (94%) with a second-generation ALK-TKI. The median follow-up from lorlatinib initiation was 23.3 months. The median PFS, median overall survival (OS) from lorlatinib initiation and median OS from advanced NSCLC diagnosis were 9.9 months (95% confidence interval [CI] 6-12.3 months), 32.9 months (95% CI 18.7 months to not reached) and 97.3 months (95% CI 75.7-152.8 months), respectively. The median duration of treatment with lorlatinib was 11.8 months (95% CI 8.5-18.8 months). Overall response and disease control rate were 49% and 86%, respectively. Central nervous system objective response rate was 56%. Treatment was stopped due to toxicity in 28 patients (14%). The safety profile of lorlatinib was consistent with previously published data. Conclusions: Real-world evidence indicates that lorlatinib offers a significant clinical benefit and high intracerebral antitumour activity in heavily pretreated patients with ALK+ NSCLC.

Telomere length appears to correlate with survival in early non-small-cell lung cancer (NSCLC), but the prognostic impact of telomere status in advanced NSCLC remains undetermined. Our purpose was to evaluate telomere parameters as prognostic and predictive biomarkers in advanced NSCLC. In 79 biopsies obtained before treatment, we analyzed the telomere length and expression of TERT and shelterin complex genes (TRF1, TRF2, POT1, TPP1, RAP1, and TIN2), using quantitative PCR. Non-responders to first-line chemotherapy were characterized by shorter telomeres and low RAP1 expression (p = 0.0035 and p = 0.0069), and tended to show higher TERT levels (p = 0.058). In multivariate analysis, short telomeres were associated with reduced event-free (EFS, p = 0.0023) and overall survival (OS, p = 0.00041). TERT and TRF2 overexpression correlated with poor EFS (p = 0.0069 and p = 0.00041) and OS (p = 0.0051 and p = 0.007). Low RAP1 and TIN2 expression-levels were linked to reduced EFS (p = 0.00032 and p = 0.0069) and OS (p = 0.000051 and p = 0.02). Short telomeres were also associated with decreased survival after nivolumab therapy (p = 0.097). Evaluation of telomere status in advanced NSCLC emerges as a useful biomarker that allows for the selection of patient groups with different clinical evolutions, to establish personalized treatment.

Chemotherapy-induced peripheral neuropathy (CIPN) is challenging for oncologists. Many publications mention the high incidence of CIPN and the lack of effective preventive/management strategies and robust diagnostic tools. This cross-sectional study was aimed at assessing the practice of French oncologists for CIPN prevention, diagnosis and management. This web-based survey was sent to French oncologists by the regional cancer networks. Incidence and impact of CIPN were assessed using visual analogue scales (VAS) and diagnostic strategies were recorded. Also recorded were the drugs used to prevent or manage CIPN and their perceived efficacy and safety (VAS). Among the 210 oncologists included, the perceived incidence of CIPN was about 36.2 ± 22.1% of patients. About 99.5% of oncologists declared that they assess CIPN during medical follow-up. The use of drugs to prevent CIPN was reported by 9.6% of oncologists (group B vitamins (35.0%) and calcium and magnesium infusion (25.0%)). In the case of CIPN, the therapeutic adjustment of neurotoxic anticancer drugs is performed by 99.0% of oncologists (chemotherapy change (49.8%), dose reduction (30.9%) or interruption (19.3%)). The pharmacological management of CIPN was declared by 72.9% of oncologists. The main drugs used are pregabalin (75.8%), amitriptyline (32.7%) and gabapentin (25.5%). Duloxetine (ASCO recommendation) is used by only 11.8% of oncologists. Oncologists were clearly aware of CIPN risks, but its incidence tended to be underestimated and the ASCO recommendations for the management of CIPN were not followed. The prevention, diagnosis and management of CIPN remain problematic in clinical practice in France. ClinicalTrials.gov : NCT03854864

BACKGROUND AND OBJECTIVES:The use of ultra-sensitive diagnostic tests to detect clinically actionable somatic alterations within the gene encoding the epidermal growth factor receptor (EGFR) within circulating cell-free DNA is an important first step in determining the eligibility of patients with non-small cell lung cancer to receive tyrosine kinase inhibitors. METHODS:We present the clinical validation (accuracy, sensitivity, and specificity) of a highly sensitive OncoBEAMTM EGFR V2 test, which we compare to a custom next-generation sequencing assay, for the treatment of patients with non-small cell lung cancer with EGFR tyrosine kinase inhibitor therapies. The OncoBEAMTM digital-polymerase chain reaction method detects 36 different EGFR alterations in circulating cell-free DNA, whereas the next-generation sequencing assay covers major solid tumor oncodrivers. Of the 540 samples analyzed with the OncoBEAMTM EGFR V2 test, 42.4% of patients had undergone molecular testing at diagnosis (N = 229/540) and 57.7% of patients during disease progression (N = 311/540). RESULTS:The sensitivity and specificity were measured for this BEAMing assay. The number of mutant beads and mutant allelic fraction were measured for each EGFR alteration and the level of detection was established at 0.1% for a median of 2861 genome equivalent (GE) in each reaction using HD780 horizon control DNA, as well as by an internal quality reference standard. Approximately 10%, 27%, and 63% of the 540 samples contained < 1500 GE, a range of 1500-3000 GE, and > 3000 GE, which corresponded to a maximal assay sensitivity of 2.0%, 0.5-0.1%, and 0.1-0.05% mutant allelic fraction, respectively. In a routine hospital setting, 11.4% of non-small cell lung cancer tumors were positive at diagnosis for EGFR alterations, while 43.7% samples harbored EGFR mutations at progression, among which 40.3% expressed EGFR resistance mutations after first-line tyrosine kinase inhibitor treatment with first- and second-generation drugs. CONCLUSIONS:The OncoBEAMTM EGFR V2 is a sensitive, robust, and accurate assay that delivers reproducible results. Next-generation sequencing and BEAMing technologies act complementarily in the routine molecular screening. We show that using a next-generation sequencing assay, despite its lower sensitivity, enables the identification of rare EGFR alterations or resistance mechanisms (mutation, deletion, insertion, and copy number variation) to orient first- and second-line treatments.

Background: The IFCT-1603 trial evaluated atezolizumab in small cell lung cancer (SCLC). The purpose of the present study was to determine whether circulating tumor DNA (ctDNA), prospectively collected at treatment initiation, was associated with the prognosis of SCLC, and whether it identified patients who benefited from atezolizumab. Methods: 68 patients were included in this study: 46 patients were treated with atezolizumab and 22 with conventional chemotherapy. Circulating DNA was extracted from plasma and NGS (Next Generation Sequencing) looked for mutations in the TP53, RB1, NOTCH1, NOTCH2, and NOTCH3 genes. ctDNA was detectable when at least one somatic mutation was identified, and its relative abundance was quantified by the variant allele fraction (VAF) of the most represented mutation. Results: We found that 49/68 patients (70.6%) had detectable baseline ctDNA. The most frequently identified mutations were TP53 (32/49; 65.3%) and RB1 (25/49; 51.0%). Patients with detectable ctDNA had a significantly lower disease control rate at week 6 compared with patients with no detectable ctDNA, regardless of the nature of the treatment. Detection of ctDNA was associated with a poor OS prognosis. The detection of ctDNA at a relative abundance greater than the median value was significantly associated with poor overall survival (OS) and progression free survival (PFS). Interestingly, the benefit in overall survival (OS) associated with low ctDNA was more pronounced in patients treated with atezolizumab than in patients receiving chemotherapy. Among patients whose relative ctDNA abundance was below the median, those treated with atezolizumab tended to have higher OS than those in the chemotherapy arm. Conclusion: ctDNA is strongly associated with the prognosis of SCLC patients treated with second-line immunotherapy. Its analysis seems justified for future SCLC clinical trials.

Background. - End-of-life (EOL) communication is crucial, particularly for cancer patients. While advanced care planning is still uncommon, we sought to investigate its impact on care intensity in case of organ failure in lung cancer patients. Methods. - We prospectively included consecutive lung cancer patients hospitalised at the Grenoble University Hospital, France, between January 1, 2014 and March 31, 2016. Patients could be admitted several times and benefited from advanced care planning based on three care intensities: intensive care, maximal medical care, and exclusive palliative care. Patients' wishes were addressed. Results. - Data of 739 hospitalisations concerning 482 patients were studied. During the three first admissions, 173 (25%) patients developed organ failure, with intensive care proposed to 56 (32%), maximal medical care to 104 (60%), and exclusive palliative care to 13 (8%). Median time to organ failure was 9 days [IQR 25%-75%: 3-13]. All patients benefited from care intensity that was either equal to or lower than the care proposed. Specific wishes were recorded for 158 (91%) patients, with a discussion about EOL conditions held in 116 (73%). Conclusions. - In case of organ failure, advanced care planning helps provide reasonable care intensity. The role of the patient's wishes as to the proposed care must be further investigated.

BACKGROUND: Resection surgery is the main treatment for non-small cell lung cancer (NSCLC). Postoperative complications and mortality are mostly linked to respiratory failure consecutive to respiratory muscle overload. AIM: We aimed to evaluate the effect of preoperative respiratory muscle endurance training (RMET) on respiratory muscle capacity and postoperative complications in patients undergoing NSCLC resection. DESIGN: Randomized controlled trial. SETTING: French university hospital. POPULATION: Patients eligible for NSCLC resection. METHODS: The training group (T group) performed a 3-week preoperative RMET added to usual chest physical therapy while the control group (C group) had only the latter. The primary outcome was the change in respiratory muscle endurance. Secondary outcomes were postoperative complications and mortality. Assessments were performed similarly at baseline and after the intervention. We conducted multivariable analyses with analysis of covariance (ANCOVA) taking into account baseline values for isocapnic hyperpnoea endurance test, exercise capacity and pulmonary function tests. The number of pulmonary postoperative complication was analyzed by Fisher-exact test. RESULTS: We included 26 patients with NSCLC (14 in the T group and 12 in the C group). Respiratory muscle endurance significantly increased in the T group after the RMET compared with C group (+229 +/- 199 vs. -5 +/- 371 sec, P=0.001). This increase was associated with a significantly lower number of pulmonary postoperative complications (2 vs. 10, P=0.037). CONCLUSIONS: Preoperative RMET improved respiratory muscle endurance and decreased pulmonary postoperative complications after surgery for NSCLC. These positive results obtained after RMET may help improve the perioperative course for such patients. These results should be confirmed in larger randomized controlled trials, including higher number of patients especially with altered respiratory muscle function. CLINICAL REHABILITATION IMPACT : Low-cost and easy to perform, RMET training could serve as complementary tool to usual chest physical therapy, before lung resection surgery.

Based on the positive results of the PACIFIC trial, AstraZeneca opened an early access program (EAP) to provide durvalumab to unresectable stage III non-small cell lung cancer (NSCLC) patients with a performance status≤2, who have not progressed after treatment with concurrent or sequential chemoradiation therapy (CRT), regardless of tumor PD-L1 expression. Pacific Real World (Pacific R) is an observational cohort study of patients who have received at least one dose of durvalumab as part of the EAP between September 2017 and December 2018. Data are collected from routine clinical care by chart abstractions at specified intervals up to five years after the patient was enrolled in the EAP. This study will enroll up to 1200 patients from France, Germany, Italy, Spain, the UK, the Netherlands, Norway, Belgium, Switzerland, Israel and Australia. A preliminary description of the first 615 patients is presented here. At time of this analysis, all countries except the UK and Spain have enrolled patients. The cohort was mostly male (67.7%) with a mean age of 64.1 years; 28.4% were ≥70 years. Nearly all patients (91.7%) had a history of smoking. Hypertension (28.6%) and COPD (25.5%) were the most frequently reported comorbidities. PDL-1 and EGFR testing were reported for 67.5% and 44% of participants, respectively. Patients had an initial diagnosis of stage III (43.4% IIIA, 45.3% IIIB, 6.9% IIIC). Adenocarcinoma (56.9%) and squamous (33.4%) were the most common histologies. Cisplatin/vinorelbine and carboplatin/paclitaxel were the most commonly administered chemotherapies prior to durvalumab. The average duration and total dose of radiotherapy was 6.95 weeks and 62.9 Gray. Most (85%) of Pacific R patients received concurrent CRT. Further CRT details, PDL1/EGFR rate will be in the poster. This preliminary analysis of a stage III unresectable NSCLC cohort provides insight into makeup of the Pacific R cohort. Future analyses will focus on progression-free survival, overall survival, duration of durvalumab and adverse events of special interest (e.g. pneumonitis, interstitial lung disease).

Le cancer du poumon est la première cause de mortalité en France et dans le monde. Le cancer bronchique non à petites cellules (CBNPC) est le sous-type histologique le plus fréquent. Malgré les progrès thérapeutiques récents avec notamment l’introduction d’immunothérapie, le CBNPC est souvent diagnostiqué à stade avancé et son pronostic est péjoratif. La dysfonction des télomères est une étape clé du processus tumoral et l’étude du statut télomérique dans le CBNPC pourrait apporter les nouveaux biomarqueurs pour mieux évaluer le pronostic et la réponse au traitement. Nous avons recherché une corrélation entre le statut télomérique et la survie dans le CBNPC métastatique. Les acides nucléiques (ADN et ARN) ont été extraits à partir de 89 biopsies tumorales. Le statut télomérique a été évalué par la longueur des télomères, l’expression de TERT (télomérase) et des gènes du complexe Shelterin impliqués dans la régulation de la maintenance des télomères (TRF1, TRF2, POT1, TPP1, RAP1 et TIN2) par PCR quantitative. Des télomères courts et une surexpression de TERT étaient associés à la survie globale (SG) plus courte (p = 0,0053 et p = 0,05, respectivement). Une forte expression de TRF2 (p = 0,025) et une faible expression de RAP1 et TIN2 (p = 0,0037 et p = 0,017, respectivement) était également corrélée à la SG réduite. De façon très intéressante, un raccourcissement des télomères influençait négativement la SG dans le sous-groupe de patients ayant reçu une immunothérapie (p = 0,0037). À notre connaissance, il s’agit de la première étude analysant le statut télomérique dans le CBNPC métastatique. Nous avons démontré que la dysfonction télomérique était associée au mauvais pronostic et à la résistance au traitement. Ainsi, la détermination de ces paramètres pourrait permettre d’ajuster les thérapies proposées aux patients et représente une voie d’espoir pour le développement de nouveaux traitements ciblés.

Background Among pts with St III unresectable NSCLC, only 15% are alive at 5 years with the historical Standard of Care (SoC) of definitive cCRT. Durvalumab, a human monoclonal anti-PD-L1 antibody, demonstrated efficacy in PFS and OS and was approved in Europe on September 2018 for the treatment of St III unresectable NSCLC expressing PD-L1 ≥ 1% and without progression after CRT. ATU permits the access to innovative medicines for pts without alternatives before a market authorization is granted. Methods Durvalumab was administrated to pts as a 60 min intravenous infusion at 10 mg/kg every 2 weeks for a maximum of 12 months, or discontinuation due to progressive disease, Adverse Events (AE) or switch to commercial drug. Pts characteristics and safety data were prospectively collected during cATU. Results From March 26th to October 28th 2018, 188 sites requested a cATU for 591 pts with St III unresectable NSCLC who did not progress after cCRT, independently of their PD-L1 status. 561 pts were treated by Durvalumab (27 pts were treated with the commercial drug & 3 pts were lost to follow-up). 71.6% of pts were men, median age was 62.4±8.9 years. 51.7% of tumours were adenocarcinoma. 40.5% of pts were in St IIIA, 51.8% in St IIIB and 6.2% in St IIIC. All pts were treated with platinum-based cCRT, with a median dose of 66 Gy [45.0-74.0] and 54% with cisplatin-based chemotherapy. Best response to cCRT was partial response for 78.5% of pts, complete response for 6.3% and stable disease for 15.2%. By January 2019, 82.1 % of pts were still under Durvalumab and 46.3% pts treated more than 6 months. Overall, drug related AEs occurred in 17.3% of pts including 8.2% serious AEs. Most common Durvalumab related AEs (all grades) were hyperthyroidism (1.2%) and pneumonitis (1.1% or n = 6, including one death). Discontinuation occurred in 17.8% of pts, of which 5.2% were Durvalumab related. Conclusions These data confirm that Durvalumab has a manageable safety profile in real-life practice. Enrollment of 591 pts in 7 months highlights the high unmet need for stage III unresectable NSCLC pts and supports Durvalumab treatment as the new SoC. Legal entity responsible for the study AstraZeneca. Funding AstraZeneca. Disclosure V. Avrillon: Advisory / Consultancy: Bristol-Myers Squibb (BMS); Travel / Accommodation / Expenses, congress invitation: Merck Sharp & Dohme (MSD); Advisory / Consultancy: AbbVie; Advisory / Consultancy: Bristol-Myers Squibb (BMS); Advisory / Consultancy: AbbVie; Travel / Accommodation / Expenses: MSD. E. Pichon: Travel / Accommodation / Expenses: Bristol-Myers Squibb (BMS); Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Merck Sharp & Dohme (MSD). A.T. Stancu: Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Bristol-Myers Squibb (BMS). C. Chouaid: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Clovis; Advisory / Consultancy: Glaxosmithkline; Advisory / Consultancy: Hoffmann-La Roche; Advisory / Consultancy: Lilly; Advisory / Consultancy: Pfizer; Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Amgen. A. Lagrange: Travel / Accommodation / Expenses: Hoffmann-La Roche; Travel / Accommodation / Expenses: Takeda; Travel / Accommodation / Expenses: Bristol-Myers Squibb (BMS). M. Sabatini: Travel / Accommodation / Expenses: Sos Oxygene; Advisory / Consultancy: BMS; Travel / Accommodation / Expenses: Boehringer Ingelheim. G. Eberst: Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: boehringer ingelheim. P. Boisselier: Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: MSD; Honoraria (self): Merck Serono; Honoraria (self): BMS; Honoraria (self): Roche. All other authors have declared no conflicts of interest.