Characterization of Patients with EGFR Mutation-Positive NSCLC Following Emergence of the Osimertinib Resistance Mutations, L718Q or G724S: A Multicenter Retrospective Observational Study in France.

Purpose: The third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), osimertinib, is an effective first-line therapy for patients with common EGFR mutation-positive non-small cell lung cancer (NSCLC). However, almost all patients become resistant to treatment. In some patients, emergence of tertiary EGFR mutations is implicated as a resistance mechanism. This study describes patients with NSCLC who acquired the rare EGFR mutations, L718Q or G724S, following EGFR TKI treatment. Patients and Methods: This was a retrospective, observational study undertaken in France from Feb-Nov 2021, in patients with EGFR mutation-positive NSCLC with an acquired L718Q or G724S mutation. Primary objectives were description of tumor characteristics, progression, and progression under treatment. Results: Nine eligible patients were identified. Acquired resistance to initial EGFR TKI treatment was associated with T790M emergence in six patients, who then received osimertinib monotherapy. Overall, eight patients received osimertinib monotherapy treatment at some point (average treatment duration: 18.3 months). Following the emergence of L718Q or G724S, patients received chemotherapy (n = 4; two of whom subsequently received afatinib), nivolumab (n = 2), afatinib (n = 2), or immunochemotherapy (n = 1). In the four patients who received afatinib after identification of L718Q or G724S, 2 achieved a partial response, one had stable disease and one had progressive disease. Treatment duration was 1.6-31.7 months. In patients with controlled disease (n = 3), progression-free survival was 6.1-31.7 months. Two of these patients had previously received osimertinib. Conclusion: Currently, there is no consensus regarding the treatment of EGFR mutation-positive NSCLC following emergence of the osimertinib resistance mutations, L718Q or G724S. Afatinib appears to be a promising treatment option in this setting.

Safety and Patient-Reported outcomes of atezolizumab plus chemotherapy with or without bevacizumab in stage IIIB/IV non-squamous non-small cell lung cancer with EGFR mutation, ALK rearrangement or ROS1 fusion progressing after targeted therapies (GFPC 06-2018 study).

BACKGROUND: In an open-label multicenter non-randomized non-comparative phase II study in patients with stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC), oncogenic addiction (EGFR mutation or ALK/ROS1 fusion), with disease progression after tyrosine-kinase inhibitor and no prior chemotherapy (NCT04042558), atezolizumab, carboplatin, pemetrexed with or without bevacizumab showed some promising result. Beyond the clinical evaluation, we assessed safety and patient-reported outcomes (PROs) to provide additional information on the relative impact of adding atezolizumab to chemotherapy with and without bevacizumab in this population. MATERIALS: Patients received platinum-pemetrexed-atezolizumab-bevacizumab (PPAB cohort) or, if not eligible, platinum-pemetrexed-atezolizumab (PPA cohort). The incidence, nature, and severity of adverse events (AEs) were assessed. PROs were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-Core 30 and EORTC QLQ-Lung Cancer 13). RESULT: Overall, 68 (PPAB) and 72 (PPA) patients were evaluable for safety. Grade 3-4 AEs occurred in 83.8% (PPAB) and 63.9% (PPA). Grade 3-4 atezolizumab-related AEs occurred in 29.4% and 19.4%, respectively. Grade 3-4 bevacizumab-related AEs occurred in 36.8% (PPAB). Most frequent grade 3-4 AEs were neutropenia (19.1% in PPAB; 23.6% in PPA) and asthenia (16.2% in PPAB; 9.7% in PPA). In PPAB, we observed a global stability in global health security (GHS) score, fatigue and dyspnea with a constant tendency of improvement, and a significant improvement in cough. In PPA, we observed a significant improvement in GHS score with a significant improvement in fatigue, dyspnea and cough. At week 54, we observed an improvement from baseline in GHS score for 49.2% of patients. In both cohorts, patients reported on average no clinically significant worsening in their overall health or physical functioning scores. CONCLUSION: PPAB and PPA combinations seem tolerable and manageable in patients with stage IIIB/IV non-squamous NSCLC with oncogenic addiction (EGFR mutation or ALK/ROS1 fusion) after targeted therapies.

Leveraging G-CSF prescribing in the outpatient setting: considerations beyond clinical factors-a questionnaire study.

PURPOSE: This study aims to delineate G-CSF treatment practices, assess decision criteria, and measure their implementation in ambulatory settings for patients with breast (BC), lung (LC), or gastrointestinal cancers (GIC), beyond standard recommendations. METHODS: In this non-interventional, cross-sectional, multicenter study, clinical cases were presented using conversational interfaces (chatbots), simulating a conversation with one or more virtual interlocutors through voice or text exchange. The clinical simulations were configured by four parameters: types of cancer, risk of FN related to chemotherapy and comorbidities, access to care, and therapy setting (adjuvant/neoadjuvant/metastatic). RESULTS: The questionnaire was completed by 102 physicians. Most practitioners (84.5%) reported prescribing G-CSF, regardless of tumor type. G-CSF was prescribed more frequently for adjuvant/neoadjuvant therapy than for metastatic cases. The type of chemotherapy was cited as the first reason for prescribing G-CSF, with access to care being the second. Regarding the type of chemotherapy, physicians do not consider this factor alone, but combined with comorbidities and age (56.7% of cases). Pegfilgrastim long-acting was prescribed in most cases of BC and LC (70.1% and 86%, respectively), while filgrastim short-acting was named in the majority of cases of GIC (61.7%); 76.3% of physicians prescribed G-CSF as primary prophylaxis. CONCLUSIONS: Our findings suggest that recommended practices are broadly followed. In the majority of cases, G-CSF is prescribed as primary prophylaxis. In addition, physicians seem more inclined to prescribe G-CSF to adjuvant/neoadjuvant patients rather than metastatic patients. Finally, the type of chemotherapy tends to be a more significant determining factor than the patient's background.

Antibody-Drug Conjugates as Novel Therapeutic Agents for Non-Small Cell Lung Carcinoma with or without Alterations in Oncogenic Drivers.

Antibody-drug conjugates (ADCs) are an emerging class of therapeutics for lung cancer, and several are currently in development for this malignancy. The structure of these molecules is based on an antibody that targets a protein on the lung cancer cell surface and a cytotoxic payload attached by a linker. Many protein targets, including TROP2, c-MET, CEACAM5, HER2, and HER3 have been identified. In metastatic non-small cell lung carcinoma (NSCLC) without alterations in oncogenic drivers, platinum-based chemotherapy and immune checkpoint inhibitors (ICIs) targeting the programmed death-1/programmed death-ligand 1 (PD1/PDL1) interaction are the standard first-line treatments. In patients with EGFR-mutated or ALK-rearranged NSCLC, tyrosine kinase inhibitors (TKIs) are recommended. However, although the prognosis of patients with metastatic NSCLC differs between such with and without alterations in oncogenic drivers, most patients eventually experience disease progression. A novel therapeutic class is needed in routine practice to overcome the mechanisms of resistance to ICIs and EGFR/ALK TKIs. Several ADCs have already been approved for other cancers, such as breast cancer and urothelial carcinoma. This review summarizes the knowledge about the efficacy and tolerance profiles of ADCs targeting TROP2, HER2, HER3, CEACAM5 and c-MET in metastatic NSCLC with and without alterations in oncogenic drivers.

First-line concomitant EGFR-TKI + chemotherapy versus EGFR-TKI alone for advanced EGFR-mutated NSCLC: a meta-analysis of randomized phase III trials.

INTRODUCTION: A tyrosine-kinase inhibitor (TKI) is indicated as a first-line treatment for patients with non-small-cell lung cancer (NSCLC) harboring an epidermal growth-factor - receptor (EGFR) mutation. Chemotherapy (ChT) given in combination with an EGFR-TKI in this setting is of interest. METHODS: We conducted a meta-analysis of phase III randomized trials comparing EGFR-TKI + ChT vs. EGFR-TKI alone as first-line therapy for advanced NSCLC harboring an activating EGFR mutation. RESULTS: Three studies evaluated gefitinib + ChT (NEJ009, GAP-Brain, and Noronha et al.) and another evaluated osimertinib + ChT (FLAURA-2). Those four eligible studies included 1413 patients with non-squamous NSCLCs, 826 (58%) with an exon-19 deletion (ex19del) and 541 (38%) with EGFRL858R. The EGFR-TKI + ChT combination was significantly associated with prolonged PFS (hazard ratio [HR]: 0.52 [95% confidence interval (CI): 0.45-0.59]; p < 0.0001) and OS (HR: 0.69 [0.52-0.93]; p = 0.01). PFS was particularly improved for patients with brain metastases (HR: 0.41[0.33-0.51]; p < 0.00001). CONCLUSIONS: For patients with untreated, advanced, EGFR-mutated NSCLCs, the EGFR-TKI + ChT combination, compared to EGFR-TKI alone, was associated with significantly prolonged PFS and OS. However, further studies are needed to identify which patients will benefit the most from the combination. REGISTRATION: PROSPERO CRD42024508055.

Plasma tissue factor activity in lung cancer patients predicts venous thromboembolism and poor overall survival.

Background: Biomarkers to identify lung cancer (LC) patients with high risk of venous thromboembolism (VTE) are needed. Objectives: To evaluate the usefulness of plasma tissue factor activity (TFA) and D-dimer levels for the prediction of VTE and overall survival in patients with LC. Methods: In a prospective multicenter observational cohort of consecutive LC patients, TFA and D-dimer levels were measured at diagnosis before any cancer treatment (V1) and between 8 and 12 weeks after diagnosis (V2). Results: Among 302 patients, 38 (12.6%) experienced VTE within the first year after diagnosis. V1-TFA and V1-D-dimer levels were significantly (P = .02) higher in patients who presented VTE within 3 months than in patients without VTE: V1-TFA was 2.02 (25th-75th percentiles, 0.20-4.01) vs 0.49 (0.20-3.09) ng/mL and V1-D-dimer was 1.42 (0.64-4.40) vs 0.69 (0.39-1.53) µg/mL, respectively. Cutoffs of 1.92 ng/mL for TFA and 1.26 µg/mL for D-dimer could discriminate both groups of patients. In multivariate analysis, V1-TFA > 1.92 ng/mL was the only significant predictor of VTE risk at 1 year (hazard ratio, 2.10; 95% CI, 1.06-4.16; P = .03). V2-TFA, quantified in 251 patients, decreased significantly compared with V1-TFA (0.20 vs 0.56 ng/mL, P < .05), but a V2-TFA level > 0.77 ng/mL could predict VTE in the following 3 months. Median overall survival was worse for patients with V1-TFA > 1.92 ng/mL (14.6 vs 23.8 months) and V1-D-dimer > 1.26 µg/mL (13.8 vs 24 months, P < .001). Conclusion: High plasma TFA levels are associated with the occurrence of VTE within the next 3 months after each visit (V1 or V2) and poor survival.

Impact of Early Access Reform on Oncology Innovation in France: Approvals, Patients, and Costs.

BACKGROUND: An ambitious reform of the early access (EA) process was set up in July 2021 in France, aiming to simplify procedures and accelerate access to innovative drugs. OBJECTIVE: This study analyzes the characteristics of oncology drug approvals through the EA process and its impact on real-life data for oncology patients. METHODS: The number and characteristics of EA demands concerning oncology drugs submitted to the National Health Authority (HAS, Haute Autorité de Santé) were reviewed until 31 December 2022. A longitudinal retrospective study on patients treated with an EA oncology drug between 1 January 2019 and 31 December 2022 was also performed using the French nationwide claims database (Systeme National des Données de Santé [SNDS]) to assess the impact of the reform on the number of indications and patients, and the costs. RESULTS: Among 110 published decisions, the HAS granted 88 (80%) EA indications within 70 days of assessment on average, including 46 (52%) in oncology (67% in solid tumors and 33% in hematological malignancies). Approved indications were mostly supported by randomized phase III trials (67%), whereas refused EA relied more on non-randomized (57%) trials. Overall survival was the primary endpoint of 28% of EA approvals versus none of denied EAs. In the SNDS data, the annual number of patients with cancer treated with an EA drug increased from 3137 patients in 2019 to 18,341 in 2022 (+ 484%), whereas the number of indications rose from 12 to 62, mainly in oncohematology (n = 17), lung (n = 12), digestive (n = 9) and breast cancer (n = 9). Reimbursement costs for EA treatments surged from €42 to €526 million (+ 1159%). CONCLUSION: The French EA reform contributed to enabling rapid access to innovations in a wide range of indications for oncology patients. However, the findings highlight ongoing challenges in financial sustainability, warranting continued evaluation and adjustments.

Outcomes of Patients with Non-Small Cell Lung Cancer and Brain Metastases Treated with the Upfront Single Agent Pembrolizumab: A Retrospective and Multicentric Study of the ESCKEYP GFPC Cohort.

Non-small cell lung cancer (NSCLC) is the most common cause of brain metastasis (BM). Little is known about immune checkpoint inhibitor activity in the central nervous system, especially in patients receiving monotherapy for tumors with a tumor proportion score (TPS) ≥ 50%. This noninterventional, retrospective, multicenter study, conducted with the GFPC, included treatment-naïve patients strongly positive for PD-L1 (TPS ≥ 50%) with BM receiving first-line single-agent pembrolizumab treatment between May 2017 and November 2019. The primary endpoints were centrally reviewed intracranial overall response rates (ORRs), centrally reviewed intracranial progression-free survival (cPFS), extracranial PFS, and overall survival were secondary endpoints. Forty-three patients from five centers were included. Surgical or local radiation therapy was administered to 31 (72%) patients, mostly before initiating ICI therapy (25/31). Among 38/43 (88.4%) evaluable patients, the intracranial ORR was 73%. The median PFS was 8.3 months. The cerebral and extracerebral median PFS times were 9.2 and 5.3 months, respectively. The median OS was 25.5 months. According to multivariate analysis, BM surgery before ICI therapy was the only factor significantly associated with both improved PFS (HR = 0.44) and OS (HR = 0.45). This study revealed the feasibility and outcome of front-line pembrolizumab treatment in this population with BM.

Resected EGFR-mutated non-small-cell lung cancers: incidence and outcomes in a European population (GFPC Exerpos Study).

Background: Few epidemiological data are available on surgically treated Caucasian patients with non-small-cell lung cancers (NSCLCs) harboring epidermal growth factor receptor (EGFR) mutations. The main objective of this study was to describe, in the real-world setting, these patients' incidence, clinical, and tumoral characteristics. Methods: The participating centers included all consecutive localized non-squamous NSCLC patients undergoing surgery between January 2018 and December 2019 in France. EGFR status was determined retrospectively when not available before surgery. Results: The study includes 1391 no squamous NSCLC patients from 16 centers; EGFR status was determined before surgery in 692 (49.7%) of the cases and conducted as part of the study for 699 (50.3%); 171 (12.3%) were EGFR mutated; median age: 70 (range: 36-88) years; female: 59.6%; never smokers: 75.7%; non-squamous histology 97.7%, programmed death ligand-1 expression 0%/1-49%/⩾50 in 60.5%/25.7%/13.8%, respectively. Surgery was predominantly lobectomy (81%) or segmentectomy (14.9%), with systematic lymph node dissection in 95.9%. Resection completeness was R0 for 97%. Post-surgery staging was as follows: IA: 52%, IB: 16%, IIA: 4%, IIB: 10%, IIIA: 16%, and IIIB: 0.05%; EGFR mutation exon was Del19/exon 21 (L858R)/20/18 in 37.4%/36.8%/14%, and 6.4% of cases, respectively; 31 (18%) patients received adjuvant treatment (chemotherapy: 93%, EGFR tyrosine kinase inhibitor: 0%, radiotherapy: 20%). After a median follow-up of 31 (95% confidence interval: 29.6-33.1) months, 45 (26%) patients relapsed: 11/45 (24%) locally and 34 (76%) with metastatic progression. Median disease-free survival (DFS) and overall survival were not reached and 3-year DFS was 60%. Conclusion: This real-world analysis provides the incidence and outcomes of resected EGFR-mutated NSCLCs in a European patient cohort.

Impact of the COVID-19 Pandemic on COPD Patient Mortality: A Nationwide Study in France.

Objectives: We investigated the mortality patterns of chronic obstructive pulmonary disease (COPD) patients in France relative to a control population, comparing year 2020 to pre-pandemic years 2017-2019. Methods: COPD patient and sex, age and residence matched control cohorts were created from the French National Health Data System. Survival was analyzed using Cox regressions and standardized rates. Results: All-cause mortality increased in 2020 compared to 2019 in the COPD population (+4%), but to a lesser extent than in the control population (+10%). Non-COVID-19 mortality decreased to a greater extent in COPD patients (-5%) than in the controls (-2%). Death rate from COVID-19 was twice as high in the COPD population relative to the control population (547 vs. 279 per 100,000 person-years). Conclusion: The direct impact of the pandemic in terms of deaths from COVID-19 was much greater in the COPD population than in the control population. However, the larger decline in non-COVID-19 mortality in COPD patients could reflect a specific protective effect of the containment measures on this population, counterbalancing the direct impact they had been experiencing.

Clinical benefit of anti-PD-1/PD-L1 plus chemotherapy in first-line treatment for patients over the age of 65 or 75 with metastatic non-small cell lung cancer (NSCLC).

Anti-PD-1/PD-L1 plus chemotherapy (CT) is considered the standard of care in first line treatment of metastatic NSCLC. However, the clinical benefit of this combination in older patients is controversial. We performed a meta-analysis of phase III randomized trials that compared PD-1/PD-L1 inhibitor plus CT with CT alone in first line of treatment for older patients with advanced NSCLC. Subgroups of patients over 65 and over 75 were analyzed. The outcomes included overall survival (OS) and progression-free survival (PFS). A fixedeffect model was used. We analyzed ten trials with an anti-PD-1 (camrelizumab, cemiplimab, nivolumab, pembrolizumab, tislelizumab or toripalimab) and six trials with an anti-PD-L1 (atezolizumab, durvalumab or sugemalimab), including 3666 patients over the age of 65 (41%) and 282 patients over the age of 75 (<10%). For patients over 65 years of age, anti-PD- 1/PD-L1 + CT was significantly associated (hazard ratio [95% confidence interval]) with prolonged OS (0.79 [0.72-0.86]; p < 0.00001) and P FS (0.63 [0.58-0.68]; p < 0.00001) compared to CT alone. Survival benefits occurred in both anti-PD-1 and anti-PD-L1 trials. For patients over 75 years of age, OS benefit was not statistically significant (0.88 [0.67-1.16]; p = 0.37). For patients over the age of 65 with untreated NSCLC, the anti-PD-1/PD-L1 combination with CT, compared with CT alone, is associated with significantly improved OS and PFS. Due to the low number of patients, it is difficult to conclude for those over 75.

Disentangling the reasons why older adults do not readily participate in cancer trials: a socio-epidemiological mixed methods approach.

BACKGROUND: Few studies of the under-representation of older adults in cancer clinical trials (CTs) have encompassed the entire pathway from a trial being available in a cancer centre to the patient's invitation to participate and then agreement or refusal to participate. OBJECTIVES: The study's primary objective was to evaluate CT non-invitation and refusal rates. The secondary objectives were to identify factors associated with non-invitation and refusal and to assess experiences of CT participation from the patients' and professionals' perspectives. METHODS: Here, we used mixed methods and a socio-epidemiological approach to analyse reasons for the non-participation of eligible older patients with a solid cancer in cancer CTs in France. RESULTS: We found that non-invitation and low CT participation are mainly related to the patients' sociodemographic characteristics and living conditions (such as social isolation, being single, divorced or widowed, not having children and the absence of close family members) and the healthcare professionals' perceptions of insufficient informal support or a high homecare requirement. CONCLUSION: Our results suggest that efforts to increase fair inclusion and the participation of older adults in CTs should target the physician-patient relationship, the medical profession and hospital funding, rather than the patient alone.

Clinical Characteristics of Patients with Advanced ALK-Translocated Non-small Cell Lung Cancers and Long-Term Responses to Crizotinib (CRIZOLONG GFPC 05-19 Study).

BACKGROUND: Although ALK-translocated (ALK+) advanced non-small cell lung cancers (aNSCLCs) are currently treated with second- or third-generation ALK inhibitors (ALK-TKIs), some patients respond durably to the first-generation ALK-TKI crizotinib. OBJECTIVE: This study aimed to describe the clinical characteristics of these long-term responders. PATIENTS AND METHODS: This national, multicenter, retrospective, non-interventional study included patients with ALK+ aNSCLCs and long-term responses to first (L1)- or subsequent (≥ L2)-line crizotinib, defined, respectively, as treatments lasting > 18 and > 10 months. Median treatment duration (mDOT) was the primary endpoint. RESULTS: A total of 85 patients (32 L1 and 53 ≥ L2 responders) from 23 centers were included (receiving crizotinib between 10/24/2011-10/02/2018): median age of 59 years, 83.6% non-smokers or ex-smokers, 85.9% performance status (PS) 0/1, 94.1% with adenocarcinomas, median of one metastatic site, and 22.4% with brain metastases (BMs). After median follow-up of 73.4 [95% confidence interval, 67.5-79.9] months, respective L1 and ≥ L2 mDOTs were 43.3 [26.7-56.8] and 29.6 [22.6-35.8] months, with overall survival (OS) not reached (NR) and 116.2 [83.4-NR] months. BM presence or absence did not affect mDOT (31.4 versus 32.9 months) but significantly impacted median OS (70.6 versus 158.6 months; p = 0.0008). Progression on crizotinib was paucisymptomatic (74.1%) and oligometastatic (34.8%), especially BMs (42.4%). After crizotinib discontinuation, 65 (76.5%) patients received subsequent systemic therapy: 57 (67.1%) with second-generation ALK-TKIs. Respective mDOTs of first- and second-line post-crizotinib ALK-TKIs lasted 19.4 [14.9-25.6] and 11.1 [4.8-17.9] months, respectively. CONCLUSIONS: Most ALK+ aNSCLC patients with prolonged crizotinib efficacy had paucisymptomatic and oligometastatic disease without BMs. They subsequently benefited from a sequential strategy with other ALK-TKIs.

Characteristics, management, and healthcare resources of patients with advanced non-small-cell lung cancer surviving 5 years after nivolumab treatment initiation: A national database analysis.

BACKGROUND: Data on long-term survivors with advanced non-small-cell lung cancer (NSCLC) treated with nivolumab are available from randomized trials. Characteristics, management, and healthcare resources of those patients need to be confirmed with real-world data. METHODS: The UNIVOC retrospective observational study included all patients with advanced NSCLC recorded in the French national hospital database starting nivolumab in 2015 and followed them until December 2020. The Kaplan-Meier method estimated the overall survival (OS). A machine learning approach identified patients with similar treatment sequences. RESULTS: Within the 3,050 patients who had nivolumab initiation,5-year OS rate was 14.6 % (95 %CI 13.3 %-16.2 %). In total, data covering at least 5 years of follow-up were retrieved for 231 surviving patients. Survivors were younger, often female and had fewer comorbidities than non-survivors. Three clusters of patients with different nivolumab treatment durations were identified: 1/ Continuous nivolumab treatment; 2/ Long period of nivolumab treatment followed by chemotherapy or no treatment; 3/ Short period of nivolumab treatment then chemotherapy or no treatment. At 5 years, 61.0 % of survivors were no longer receiving systemic therapy, 26.4 % were treated with nivolumab, 8.7 % chemotherapy, and 3.9 % other immunotherapies. Among 5-y survivor patients, the average number of hospitalisations per patient decreased from 23.4 to 12.8 between the 1st and the 5th year. In the 5th year, 46 % of patients had no more hospitalization for lung cancer. CONCLUSIONS: This large nationwide study confirms the long-term benefit of nivolumab treatment for advanced NSCLC patients in the real-world setting, with a 5-year survival rate similar to that reported in clinical trials.

Three-Year Overall Survival of Patients With Advanced Non-Small-Cell Lung Cancers With ≥50% PD-L1 Expression Treated With First-Line Pembrolizumab Monotherapy in a Real-World Setting (ESCKEYP GFPC Study).

Outside clinical trials, few data are available on the effect of long-term first-line pembrolizumab in patients with advanced non-small-cell lung cancers with ≥50% of tumor cells expressing programmed cell death ligand 1 (PD-L1). This French, multicenter study included consecutive advanced patients with non-small-cell lung cancer given first-line pembrolizumab alone between May 2017 (authorization date for this indication) and November 2019 (authorization date for pembrolizumab-chemotherapy combination). Information was collected from patients' medical files, with a local evaluation of the response and progression-free survival (PFS). Overall survival (OS) was calculated from pembrolizumab onset using the Kaplan-Meier method. The analysis concerned 845 patients, managed in 33 centers: median age: 65 (range: 59-72) years, 67.8% men, 78.1% Eastern Cooperative Oncology Group performance status 0/1, 38.9%/51.5%/6.6% active, ex or never-smokers, respectively, 10.9%/16.8% taking or recently took corticosteroids/antibiotics, 69.6% nonsquamous histology, 48.9% ≥75% PD-L1-positive, and 20.8% had brain metastases at diagnosis. After a median (95% CI) follow-up of 45 (44.1-45.9) months, respective median (95% CI) PFS and OS lasted 8.2 (6.9-9.2) and 22 (8.5-25.9) months; 3-year PFS and OS rates were 25.4% and 39.4%, respectively. Multivariate analysis retained never-smoker status, adenocarcinoma histology, Eastern Cooperative Oncology Group performance status ≥2, and neutrophil/lymphocyte ratio >4 as being significantly associated with shorter survival, but not brain metastases at diagnosis or <75% PD-L1 tumor-cell expression. These long-term results of pembrolizumab efficacy based on a nationwide "real-world" cohort reproduced those obtained in clinical trials.

Venous thrombotic events and impact on outcomes in patients treated with first-line single-agent pembrolizumab in PD-L1 ≥ 50% advanced non small cell lung cancer.

BACKGROUND: Few data are available on the impact of venous thrombotic events (VTE) in patients with metastatic non-small cell lung cancer (mNSCLC) treated with immunotherapy. METHODS: This is a secondary analysis of the ESKEYP study, a national, retrospective, multicenter study that consecutively included all PD-L1 ≥ 50% mNSCLC patients who initiated first-line treatment with pembrolizumab monotherapy. From May 2017 to November 2019, 845 patients were included (from availability of pembrolizumab in this indication in France to the authorization of the combination with chemotherapy). Impact of VTE and patient characteristics were analyzed. RESULTS: Of the 748 patients (88.5%) with available data, the incidence of VTE was 14.8% (111/748). At pembrolizumab initiation, Khorana score was ≥ 2 for 55.0% (61/111) of them. Recurrence of VTE was reported for 4 of the 111 patients and 5 had bleeding complications. Patients with VTE were significantly younger, had more frequently long-term corticosteroids treatment and more often liver metastases. Progression-free survival (PFS) was significantly shorter in patients with VTE compared to patients without VTE: 6.1 (95% CI 4.1-9.0) months vs. 8.3 (6.9-10.3) months (p = 0.03). VTE did not significantly impact overall survival (OS): 15.2 (10.0-24.7) months with VTE and 22.6 (18.4-29.8) months without VTE (p = 0.07). In multivariate analysis for PFS and OS, HRs for VTE were 1.3 (0.99-1.71), p = 0.06 and 1.32 (0.99-1.76), p = 0.05. CONCLUSION: The incidence of VTE appears to be as high with in first-line immunotherapy as with chemotherapy in patients with mNSCLC, with in patient with VTE, a no significant trend for lower PFS and OS in multivariate analysis. more marked impact on PFS than on OS.

Organizational Impact of Immunotherapies in Advanced Cancers in France.

PURPOSE: In 2020, the French National Authority for Health (Haute Autorité de Santé) published a methodologic guide called organizational impact (OI) cartography to define and structure assessment of the OI of health technologies. As immunotherapies are associated with extended survival and improved quality of life in advanced cancer, we aimed to identify OIs that immunotherapies had on health care systems and professionals. To our knowledge, we suggest the first implementation for OI assessment on the basis of the cartography. METHODS: A literature review was conducted, and interviews with health care professionals (HCPs) were performed to identify OIs of immunotherapies. They were asked if immunotherapies had OIs classified into three macrocriteria, namely, impact on the care process (six criteria), impact on capacities and skills required (six criteria), and impact on society (four criteria). If an OI was mentioned for a criterion, information on its impact (minor/moderate/major) and its timing was collected. We considered that an OI existed when 75% of HCPs mentioned an impact for a given criterion. RESULTS: Overall, 27 HCPs were interviewed. For 12 of 16 criteria, most HCPs mentioned an impact, whereas the literature identified impacts for 11 criteria. Four criteria (skills and transfer between HCPs, scheduling capabilities, and social relationship) had consensus among HCPs and a high impact; two criteria (rhythm or care duration, working/living conditions) showed consensus but a moderate impact; two criteria (funding and scheduling capabilities cross-structure) had a high impact but no consensus. For eight criteria (as environment or inequity), there was no consensus and moderate impact. CONCLUSION: The introduction of immunotherapies for advanced cancer has had an important OI in France, regarding capacities and skills. Further research using qualitative analysis of interviews will provide more information regarding OI.

Cost-effectiveness analysis of atezolizumab as adjuvant treatment of patients with stage II-IIIA non-small cell lung cancer, PD-L1+≥50% of tumor cells in France: A modeling study.

INTRODUCTION: The objective of this study was to assess the cost-effectiveness of atezolizumab versus best supportive care (BSC) as adjuvant treatment following resection and platinum-based chemotherapy for patients with stage II-IIIA non-small cell lung cancer (NSCLC) whose tumours have a programmed death-ligand 1 (PD-L1) expression ≥ 50% of tumour cells and excluding those with ALK/EGFR mutations, from a French collective perspective. MATERIAL AND METHODS: A five state Markov model over a 20-year time horizon was considered, including disease-free survival (DFS1) from IMpower010 trial, three progression states (locoregional recurrence, first and second-line metastatic recurrence) and death. Utilities, quality-adjusted life year (QALY) decrements associated to adverse events, costs, resource use, and transition probabilities were considered in the model. These inputs were sourced from IMpower010 trial, literature, and clinical experts' opinion. Model uncertainty was assessed through deterministic, probabilistic sensitivity analyses and scenario analyses. RESULTS: Atezolizumab was associated with a QALY gain of 1.662, mainly driven by additional time spent in the DFS state, and a life-year gain of 2.112 years. The incremental cost-effectiveness ratio (ICER) for atezolizumab versus BSC was €21,348/QALY gained. The sensitivity analyses highlighted that uncertainty within the model had limited impact on results. Changing the DFS survival curves to other plausible distributions produced ICERs below €20,000/QALY. Introducing an increasing proportion of cured patients (91.5%) from year two to year five reduced the ICER to €13,083/QALY, while including a loss of efficacy at year two in the atezolizumab treatment arm increased the ICER to €33,755/QALY. DISCUSSION: Atezolizumab as adjuvant treatment in stage II-IIIA NSCLC resected patients with PDL1 ≥ 50% and without ALK/EGFR mutations has a lower ICER than other oncology drugs in France and a similar ICER to other adjuvant treatment in oncology.

Treatment patterns and clinical outcomes of extensive stage small cell lung cancer (SCLC) in the real-world evidence ESME cohort before the era of immunotherapy.

BACKGROUND: Small cell lung cancer (SCLC) is a highly aggressive entity of lung cancer with tendency toward early recurrence after first-line treatment. As per recently updated European Society for Medical Oncology recommendations, first-line treatment with up to 4 cycles of platinum-etoposide combined with immune checkpoint inhibitor (ICIs)-targeting PD-L1, is now the standard of care. The purpose of the current analysis is to identify current patient profiles and treatment strategies in real life clinical practice, and report outcomes in Extensive Stage (ES)-SCLC. METHODS: Non-interventional, retrospective, multicentre, comparative study was carried out to describe the outcome of ES-SCLC patients included in the Epidémiologie Stratégie Médico-Economique (ESME) data platform for advanced and metastatic lung cancer. Patients were selected from 34 health care facilities between January 2015 and December 2017, before the era of immunotherapy. RESULTS: 1315 patients were identified, including 64% male and 78% under 70 year-old; 24% had at least 3 metastatic sites, mainly liver metastases (43%), bone metastases (36%), brain metastases (32%). 49% received only one line of systemic treatment; 30% and 21% received 2 and 3 lines or more, respectively. Carboplatin was more frequently used than cisplatin (71% and 29%, respectively). Prophylactic cranial irradiation was infrequent (4% of patients), but 16% of patients received thoracic radiation therapy, mainly after the completion of first-line chemotherapy (72% of patients); such strategies were more frequently applied in cisplatin/etoposide than carboplatin/etoposide patients (p = 0.006 and p = 0.015, respectively). After a median follow-up time of 21.8 (95% CI: 20.9-23.3) months, median real-world Progression-Free Survival (rw-PFS) was 6.2 (95% CI: 5.7; 6.9) and 6.1 (95% CI: 5.8; 6.3) months for cisplatin/etoposide and carboplatin/etoposide doublet regimens, respectively; 24-month rwPFS and Overall Survival were 3.2% (95% CI: 2.3; 4;2) and 22.2% (95% CI: 19.4; 25.1) in the whole population, respectively. CONCLUSION: Our data provide with landmark reference findings on ES-SCLC before the immunotherapy era, and cover many aspects of the treatment strategy, while highlighting on the role of radiotherapy, subsequent lines of therapy, and the outcomes of patients. Generation of real-world data focusing on patients who received platinum-based chemotherapy combined with immune checkpoint inhibitors is under way.