Recommendations for reporting tissue and circulating tumour (ct)DNA next-generation sequencing results in non-small cell lung cancer.

Non-small cell lung cancer is a heterogeneous disease and molecular characterisation plays an important role in its clinical management. Next-generation sequencing-based panel testing enables many molecular alterations to be interrogated simultaneously, allowing for comprehensive identification of actionable oncogenic drivers (and co-mutations) and appropriate matching of patients with targeted therapies. Despite consensus in international guidelines on the importance of broad molecular profiling, adoption of next-generation sequencing varies globally. One of the barriers to its successful implementation is a lack of accepted standards and guidelines specifically for the reporting and clinical annotation of next-generation sequencing results. Based on roundtable discussions between pathologists and oncologists, we provide best practice recommendations for the reporting of next-generation sequencing results in non-small cell lung cancer to facilitate its use and enable easy interpretation for physicians. These are intended to complement existing guidelines related to the use of next-generation sequencing (solid and liquid). Here, we discuss next-generation sequencing workflows, the structure of next-generation sequencing reports, and our recommendations for best practice thereof. The aim of these recommendations and considerations is ultimately to ensure that reports are fully interpretable, and that the most appropriate treatment options are selected based on robust molecular profiles in well-defined reports.

Long-term benefit of sotorasib in patients with KRAS G12C-mutated non-small-cell lung cancer: plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a plain language summary of a study called CodeBreaK 100. The CodeBreaK 100 study included patients with non-small-cell lung cancer that had spread outside the lung (advanced). Lung cancer is one of the most common forms of cancer. CodeBreaK 100 specifically looked at patients with a particular change(mutation) in the KRAS gene resulting in the mutated protein called KRAS G12C. The KRAS G12C mutation can lead to development and growth of lung cancer. Patients received a treatment called sotorasib, which has accelerated approval or full approval in over 50 countries for patients with non-small-cell lung cancer with the KRAS G12C mutation. The CodeBreaK 100 study looked at whether sotorasib is a safe and effective treatment for advanced non-small-cell lung cancer. Sotorasib is designed to specifically target and lock the mutated KRAS protein in the inactive state to treat non-small-cell lung cancer. WHAT WERE THE RESULTS?: In total, 174 adults were treated with sotorasib. Treatment-related side effects were seen in 70% of patients and were severe in 21% of patients. The most common side effects included diarrhea, increased liver enzymes, nausea and tiredness. 70 (41%) patients responded to sotorasib and 144 (84%) patients had tumors that either remained stable or shrunk in size. 29 (41%) patients who responded to sotorasib responded for over 12 months. After 2 years, 9 patients with a response remained on sotorasib; there were no notable increases in tumor size or development of new tumors over this time. There were 5patients who received sotorasib for more than 2 years and continued to respond. Long-term benefit was seen for some patients. Patients also benefitted from treatment when the tumor expressed different amounts of a protein called PD-L1.In total, 33% of patients were still alive after 2 years. WHAT DO THE RESULTS MEAN?: Results show the long-term benefit of sotorasib therapy for people with advanced KRAS G12C-mutated non-small-cell lung cancer. Clinical Trial Registration: NCT03600883 (CodeBreaK 100) (ClinicalTrials.gov).

Mobocertinib in Patients with EGFR Exon 20 Insertion-Positive Non-Small Cell Lung Cancer (MOON): An International Real-World Safety and Efficacy Analysis.

EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Data from 86 patients with a median age of 67 years and a median of two prior lines of treatment were analyzed. Treatment-related adverse events (TRAEs) occurred in 95% of patients. Grade ≥3 TRAEs were reported in 38% of patients and included diarrhea (22%) and rash (8%). In 17% of patients, therapy was permanently discontinued, and two patients died due to TRAEs. Women were seven times more likely to discontinue treatment than men. In the overall cohort, the objective response rate to mobocertinib was 34% (95% CI, 24-45). The response rate in treatment-naïve patients was 27% (95% CI, 8-58). The median progression-free and overall survival was 5 months (95% CI, 3.5-6.5) and 12 months (95% CI, 6.8-17.2), respectively. The intracranial response rate was limited (13%), and one-third of disease progression cases involved the brain. Mobocertinib also showed antitumor activity following EGFR Ex20-specific therapy and vice versa. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity.

Cellular Therapy in NSCLC: Between Myth and Reality.

PURPOSE OF REVIEW: In this paper, we review the current state and modalities of adoptive cell therapies (ACT) in non-small cell lung carcinoma (NSCLC). We also discuss the challenges hampering the use of ACT and the approaches to overcome these barriers. RECENT FINDINGS: Several trials are ongoing investigating the three main modalities of T cell-based ACT: tumor-infiltrating lymphocytes (TILs), genetically engineered T-cell receptors (TCRs), and chimeric antigen receptor (CAR) T cells. The latter, in particular, has revolutionized the treatment of hematologic malignancies. However, the efficacy against solid tumor is still sparse. Major limitations include the following: severe toxicities, restricted infiltration and activation within the tumors, antigen escape and heterogeneity, and manufacturing issues. ACT is a promising tool to improve the outcome of metastatic NSCLC, but significant translational and clinical research is needed to improve its application and expand the use in NSCLC.

Current Approaches to Neoadjuvant Immunotherapy in Resectable Non-small Cell Lung Cancer.

PURPOSE OF REVIEW: For decades, early-stage resectable non-small cell lung cancer (NSCLC), while potentially curable, has been marred by unacceptably high recurrence rates. RECENT FINDINGS: Anti-PD(L)1 immune checkpoint blockade (ICB) has revolutionized the treatment of advanced NSCLC, and with recent approvals in the peri-operative space, is now poised to transform the systemic treatment paradigm for localized and locally-advanced NSCLC. In this review, we focus on neoadjuvant ICB in resectable NSCLC, highlighting the pre-clinical rationale for neoadjuvant ICB, early clinical trials, randomized phase 3 trial data, and future directions for resectable NSCLC.

Neoadjuvant Immunotherapy: A Promising New Standard of Care.

Neoadjuvant immunotherapy has emerged as a promising approach in the treatment of various malignancies, with preclinical studies showing improved immune responses in the preoperative setting. FDA-approved neoadjuvant-immunotherapy-based approaches include triple-negative breast cancer and early non-small cell lung cancer on the basis of improvement in pathological response and event free survival. Nevertheless, current trials have only shown benefits in a fraction of patients. It is therefore crucial to identify predictive biomarkers to improve patient selection for such approaches. This review aims to provide an overview of potential biomarkers of neoadjuvant immunotherapy in early triple-negative breast cancer, bladder cancer, melanoma, non-small cell lung cancer, colorectal cancer and gastric cancer. By the extrapolation of the metastatic setting, we explore known predictive biomarkers, i.e., PD-L1, mismatch repair deficiency and tumour mutational burden, as well as potential early-disease-specific biomarkers. We also discuss the challenges of identifying reliable biomarkers and the need for standardized protocols and guidelines for their validation and clinical implementation.

The Effects of GCSF Primary Prophylaxis on Survival Outcomes and Toxicity in Patients with Advanced Non-Small Cell Lung Cancer on First-Line Chemoimmunotherapy: A Sub-Analysis of the Spinnaker Study.

GCSF prophylaxis is recommended in patients on chemotherapy with a >20% risk of febrile neutropenia and is to be considered if there is an intermediate risk of 10−20%. GCSF has been suggested as a possible adjunct to immunotherapy due to increased peripheral neutrophil recruitment and PD-L1 expression on neutrophils with GCSF use and greater tumour volume decrease with higher tumour GCSF expression. However, its potential to increase neutrophil counts and, thus, NLR values, could subsequently confer poorer prognoses on patients with advanced NSCLC. This analysis follows on from the retrospective multicentre observational cohort Spinnaker study on advanced NSCLC patients. The primary endpoints were OS and PFS. The secondary endpoints were the frequency and severity of AEs and irAEs. Patient information, including GCSF use and NLR values, was collected. A secondary comparison with matched follow-up duration was also undertaken. Three hundred and eight patients were included. Median OS was 13.4 months in patients given GCSF and 12.6 months in those not (p = 0.948). Median PFS was 7.3 months in patients given GCSF and 8.4 months in those not (p = 0.369). A total of 56% of patients receiving GCSF had Grade 1−2 AEs compared to 35% who did not receive GCSF (p = 0.004). Following an assessment with matched follow-up, 41% of patients given GCSF experienced Grade 1−2 irAEs compared to 23% of those not given GCSF (p = 0.023). GCSF prophylaxis use did not significantly affect overall or progression-free survival. Patients given GCSF prophylaxis were more likely to experience Grade 1−2 adverse effects and Grade 1−2 immunotherapy-related adverse effects.

Differential prognostic effect of systemic inflammation in patients with non-small cell lung cancer treated with immunotherapy or chemotherapy: A post hoc analysis of the phase 3 OAK trial.

BACKGROUND: A proinflammatory diathesis, as measured by the neutrophil to lymphocyte ratio (NLR), heralds an adverse disease course for non-small cell lung cancer (NSCLC). METHODS: This post hoc analysis used data from the phase 3 OAK trial (NCT02008227), which randomized previously treated patients with NSCLC to atezolizumab or docetaxel. The main objective was assessing the differential impact of the pretreatment NLR on overall survival according to the treatment modality. In addition, patients' genomic characteristics were assessed according to their inflammatory status with a circulating free DNA (cfDNA) next-generation sequencing (NGS) analysis. RESULTS: In all, 600 and 575 patients with NLR data were included in the atezolizumab and docetaxel cohorts, respectively, with a median NLR of 4 (interquartile range, 2.6-6.7) for the pooled population. An NLR ≥4 was associated with a positive smoking status (88.6% vs. 78.1%; p < .01), male sex (66.4% vs. 57.6%; p = .01), a worse performance status (71.3% vs. 55.2%; p < .01), a higher number of metastatic sites (63.2% vs. 51.6%; p = .01), squamous histology (32.1% vs. 21.4%; p < .01), and tissue KRAS mutations (30% vs. 18.7%; p = .02) but not with programmed death ligand 1 (PD-L1) expression or the tissue epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) status. A pretreatment NLR ≥4 was more strongly associated with mortality after atezolizumab (adjusted hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.35-2.01) versus docetaxel (HR, 1.32; 95% CI, 1.08-1.60; multivariable [MVA] interaction p = .08). The HR for an increased risk of death for PD-L1-negative/NLR ≥4 patients (compared with PD-L1-positive/NLR <4 patients) was significantly higher in the atezolizumab cohort (MVA interaction p = .01). The exclusion of EGFR/ALK-positive patients further increased the prognostic ability of the baseline NLR in favor of atezolizumab (MVA interaction p = .02). Pretreatment cfDNA data from NGS showed that patients with a high blood tumor mutation burden (cutoff, 16 mut/Mb) had a higher median NLR (4.6 vs. 3.7; p = .01). After adjustments for multiple comparisons, none of the selected variants of interest (EGFR, KRAS, TP53, KEAP1, STK11, SMARCA4, ARID1A, and targeted DNA damage response and repair genes) were significantly associated with the NLR. CONCLUSIONS: A low baseline NLR identified patients with NSCLC who derived a greater survival benefit from atezolizumab in comparison with those identified in the docetaxel cohort. The NLR could complement PD-L1 expression in tailoring treatment in this setting.

International Survey on Frailty Assessment in Patients with Cancer.

BACKGROUND: Frailty negatively affects the outcomes of patients with cancer, and its assessment might vary widely in the real world. The objective of this study was to explore awareness and use of frailty screening tools among the ONCOassist healthcare professionals (HCPs) users. MATERIALS AND METHODS: We sent 2 emails with a cross-sectional 15-item survey in a 3-week interval between April and May 2021. Differences in the awareness and use of tools according to respondents' continents, country income, and job types were investigated. RESULTS: Seven hundred thirty-seven HCPs from 91 countries (81% physicians, 13% nurses, and 5% other HCPs) completed the survey. Three hundred and eighty-five (52%) reported assessing all or the majority of their patients; 518 (70%) at baseline and before starting a new treatment. Three hundred and four (43%) HCPs were aware of performance status (PS) scores only, 309 (42%) age/frailty/comorbidity (AFC) screening, and 102 (14%) chemotoxicity predictive tools. Five hundred and thirty-seven (73%) reported using tools; 423 (57%) just PS, 237 (32%) AFC, and 60 (8%) chemotoxicity ones. Reasons for tools non-use (485 responders) were awareness (70%), time constraints (28%), and uselessness (2%). There were significant differences in awareness and use of screening tools among different continents, country income, job types, and medical specialties (P < .001 for all comparisons). CONCLUSION: Among selected oncology HCPs, there is still a worldwide lack of knowledge and usage of frailty screening tools, which may differ according to their geography, country income, and education. Targeted initiatives to raise awareness and education are needed to implement frailty assessment in managing patients with cancer.

Risk of SARS-CoV2-Related Mortality in Non-Small Cell Lung Cancer Patients Treated with First-Line Immunotherapy Alone or in Combination with Chemotherapy.

BACKGROUND: The impact of systemic anticancer treatments on SARS-CoV-2-related mortality is still debatable. METHODS: By a retrospective analysis of patients with non-small-cell lung cancer (NSCLC) treated with first-line Pembrolizumab or in combination with chemotherapy (ChT) during the first surge of the pandemic. RESULTS: The adjusted risk of death was higher in patients treated with ChT + Pembrolizumab (HR 4.6, 1.2-17.4, p = 0.02). The SARS-CoV-2-related mortality rate was higher in patients treated with ChT + Pembrolizumab (p = 0.03), ≥70 years (p = 0.03) and current smokers (p = 0.17). CONCLUSIONS: The addition of ChT to immunotherapy could be associated with increased risk of mortality and higher SARS-CoV-2-related mortality rate.

Biological Rationale for Peripheral Blood Cell-Derived Inflammatory Indices and Related Prognostic Scores in Patients with Advanced Non-Small-Cell Lung Cancer.

PURPOSE OF REVIEW: To describe the biological rationale of peripheral blood cells (PBC)-derived inflammatory indexes and assess the related prognostic scores for patients with advanced non-small cell lung cancer (aNSCLC) treated with immune-checkpoint inhibitors (ICI). RECENT FINDINGS: Inflammatory indexes based on PBC may indicate a pro-inflammatory condition affecting the immune response to cancer. The lung immune prognostic index (LIPI), consisting of derived neutrophils-to-lymphocyte ratio (NLR) and lactate dehydrogenase, is a validated prognostic tool, especially for pretreated aNSCLC patients, where the combination of NLR and PD-L1 tumour expression might also be predictive of immunotherapy benefit. In untreated high-PD-L1 aNSCLC patients, the Lung-Immune-Prognostic score (LIPS), including NLR, ECOG PS and concomitant steroids, is prognostic, and its modified version might indicate patients with favourable outcomes despite an ECOG PS of 2. NLR times platelets (i.e., SII), included in the NHS-Lung score, might improve the prognostication for combined chemoimmunotherapy. PBC-derived inflammatory indexes and related scores represent accurate, reproducible and non-expensive prognostic tools with clinical and research utility.

[Patient involvement in oncology research - Development of a reference framework in French-speaking Switzerland]. / Implication des patients dans la recherche en oncologie - Développement d'un cadre de référence en Suisse romande.

Patient and public involvement (PPI) in research is increasingly recognized and encouraged by public and funding bodies. Although gaining momentum, the implementation of PPI in Switzerland remains recent. Since 2021, the Laboratoire des Patients, affiliated to the Swiss Cancer Center Léman (SCCL), aims to establish a PPI model for oncology research adapted to the local context that will assist researchers to apply PPI approaches within their projects. Among its functions, the Laboratoire des Patients will offer a training program for patients and researchers targeting PPI in research, support throughout the projects, and consultation and mediation services for patients and researchers. This article discusses the utility of PPI in research and describes the SCCL-PPI model.

L'implication des patients et du public (IPP) en recherche est de plus en plus reconnue et encouragée par les organismes publics et de financement. Bien qu'en accélération, l'implantation de l'IPP en Suisse reste récente. Depuis 2021, le Laboratoire des patients, affilié au Swiss Cancer Center Léman (SCCL), a pour but d'établir un modèle IPP pour la recherche en oncologie adapté au contexte local qui facilitera pour les chercheurs la mise en place des approches IPP au sein de leurs projets. Parmi ses fonctions, le Laboratoire des patients offrira des programmes de formation pour patients et chercheurs ciblant l'IPP en recherche, un accompagnement tout au long des projets, ainsi que des services de consultation et médiation pour patients et chercheurs. Cet article discute l'utilité de l'IPP en recherche et décrit le modèle SCCL-IPP.

SAKK 19/17: safety analysis of first-line durvalumab in patients with PD-L1 positive, advanced nonsmall cell lung cancer and a performance status of 2.

INTRODUCTION: The safety of first-line (1L) durvalumab in patients with advanced nonsmall-cell lung cancer (NSCLC) and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 (PS2) is unknown. This is an interim unplanned safety analysis of the study SAKK 19/17 for patients with metastatic NSCLC with programmed death-ligand 1 (PD-L1) expression in ≥ 25% of tumor cells and an ECOG PS2 treated with 1L durvalumab. This safety analysis was triggered by the SAKK data and safety monitoring board due to a high mortality rate observed after the recruitment of the first 21 patients. METHODS: This single-arm phase II study recruited patients with metastatic NSCLC with PD-L1 in ≥ 25% and ECOG PS2. Patients received durvalumab 1500 mg every four weeks. The trial aims to recruit 48 patients in total. This report includes safety analyses only. Adverse events (AEs) were assessed using National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) Version 5.0. Efficacy data including the primary endpoint overall survival at 6 months and secondary endpoints (objective response rate, progression-free survival, and quality of life) will be reported at a later time point. RESULTS: The data from 21 patients were available at this interim safety analysis. Among these, 13 deaths (13/21; 62%) were reported, including one treatment-related fatal colonic perforation at 9 months after treatment initiation (1/13; 8%). Twelve deaths were not treatment-related (12/13; 92%), and mostly attributed to tumor progression (10/13; 77%). Of note, seven deaths (7/13; 54%) occurred during the first 5 weeks (range 0.6-4.7 weeks) after treatment initiation. Four (4/7; 57%) were respiratory failures attributed to tumor progression. One of these patients (25%) had pre-existing COPD, and three (75%) had baseline dyspnea grade 2-3 related to the tumor. Grade ≥ 3 treatment-related AEs (TRAEs) included colonic perforation (grade 5), abdominal pain, and colitis (grade 3 each) in one patient, and fatigue (grade 3) in another. Other Grade ≥ 3 AEs unrelated to treatment were all of pulmonary origin: lung infections (19%), dyspnea (24%), cough (5%), and bronchial obstruction (5%). CONCLUSIONS: 1L durvalumab in patients with ECOG PS2 and metastatic NSCLC with PD-L1 expression ≥ 25% resulted in an unexpectedly high number of fatal early events due to rapid tumor progression. We recommend to avoid treatment with 1 L durvalumab of patients who are highly symptomatic from the tumor, particularly those with respiratory symptoms. The study is continuing its accrual after an amendment excluding these patients.

The Role and Impact of Minimal Residual Disease in NSCLC.

PURPOSE OF REVIEW: There has been a huge development in the assessment of malignancies through liquid biopsies last years, especially for NSCLC, where its use has become part of clinical practice in some settings. We aim to summarize current evidence about minimal residual disease and its use in lung cancer. RECENT FINDINGS: Recent studies using ctDNA in NSCLC but also in other types of cancer found strong correlations between the presence of ctDNA and the risk of disease progression or death after curative intent, despite current technical difficulties in performing this analysis (high sensitivity and specificity required). Evaluation of MRD in NSCLC, especially through ctDNA, could be an important point in future trial designs and could permit a more "targeted" adjuvant treatment.

A New Generation of Vaccines in the Age of Immunotherapy.

PURPOSE OF REVIEW: Cancer vaccines are one of the most extensively studied immunotherapy type in solid tumors. Despite favorable presuppositions, so far, the use of cancer vaccines has been associated with disappointing results. However, a new generation of vaccines has been developed, promising to revolutionize the immunotherapy field. RECENT FINDINGS: In this review, we aim to highlight the advances in cancer vaccines and the remaining hurdles to overcome. Cancer vaccination has experienced tremendous progress in the last decade, with myriad promising developments. Future efforts should focus on optimization of target identification, streamlining of most appropriate vaccination strategies, and adjuvant development, as well as predictive biomarker identification. Cautious optimism is warranted in the face of early successes seen in recent clinical trials for oncolytic vaccines. If an approach were to prove successful, it could revolutionize cancer therapy the way ICIs did in the previous decade.

[Non-small cell lung cancer: a target biology]. / Cancer pulmonaire non à petites cellules : une biologie prête à cibler.

Lung cancer is divided into two categories: small cell cancer and non-small cell lung cancer (NSCLC). Management of NSCLC has evolved considerably since the advent of immunotherapies and targeted therapies, both for the localized stages and for the advanced stages. NSCLC are no longer only subdivided by their histological characteristics but also by their molecular characteristics which constitute therapeutic targets.

Les cancers pulmonaires sont divisés en deux catégories: le cancer à petites cellules et le cancer non à petites cellules (Non Small Cell Lung Cancer (NSCLC)). La prise en charge de ce dernier a beaucoup évolué depuis l'avènement des immunothérapies et des thérapies ciblées, tant pour les stades localisés que pour les stades avancés. Les NSCLC ne sont plus seulement subdivisés par leurs caractéristiques histologiques, mais aussi par leurs caractéristiques moléculaires qui constituent des cibles thérapeutiques.

The METeoric rise of MET in lung cancer.

Over the years, there has been a continuous increase in clinically relevant driver mutations in patients with non-small cell lung cancer (NSCLC). Among these, dysregulated activation of the MET tyrosine kinase receptor has gained importance due to the recent development of quite effective treatments. MET dysregulation encompasses a heterogeneous array of alterations leading to the prolonged activation of the cellular MET (c-MET or MET) receptor and downstream proliferation pathways. It can arise through several mechanisms, including gene amplification, overexpression of the receptor and/or its ligand hepatocyte growth factor, and the acquisition of activating mutations. MET mutations are found in approximately 3% to 5% of patients with NSCLC, mainly adenocarcinoma, and are overrepresented in the sarcomatoid subtype. De novo MET amplifications are found in 1% to 5% of NSCLC cases, also predominantly in adenocarcinoma. In the current review, the authors discussed the biology of MET, how to diagnose clinically relevant alterations, and the rising clinical importance of these alterations in light of the emergence of multiple targeted therapies, both within the context of MET as a driver of resistance and in its own right.

Outcomes with immune checkpoint inhibitors for relapsed small-cell lung cancer in a Swiss cohort.

OBJECTIVES: Early clinical trials showed promising outcomes with immune-checkpoint inhibitors (ICI) in a subset of patients with relapsed small-cell lung carcinoma (SCLC). The aim of this retrospective analysis was to assess the efficacy and safety of ICI for relapsed SCLC in a real-world patient population. METHODS: Nine cancer centres in Switzerland contributed data to this cohort. Responses were assessed by the local investigators using standard RECIST v1.1 criteria. Progression-free survival (PFS) and overall survival (OS) were analysed by the Kaplan-Meier method. Associations between potential predictive markers and survival endpoints were probed by Cox proportional hazards. RESULTS: Forty-five patients were included in the analysis. Median age was 63 years, 73% were males and 18% had an ECOG performance status (PS) ≥ 2. ICIs were given as second-line treatment in 60%. Twenty-four patients (53%) received ipilimumab with nivolumab. Twenty-eight patients (62%) had undergone irradiation (RT) prior to or during ICI. Overall response rate (ORR) was 29% and median PFS and OS were 2.3 and 6.5 months, respectively. Median duration of response was 9 months (95% CI 2.8-NA). Five patients maintained their response for > 6 months, all of them receiving combination treatment. There were no new safety signals. CONCLUSION: This is the first report of "real-world" data on ICI in relapsed SCLC also including patients with poor PS. Promising durable responses were observed. No biological prognostic marker could be identified.

Impact of performance status on non-small-cell lung cancer patients with a PD-L1 tumour proportion score ≥50% treated with front-line pembrolizumab.

Objectives: We retrospectively analysed patients with advanced non-small-cell lung cancer (NSCLC) harbouring high PD-L1 expression (>50%) and treated with front-line pembrolizumab, comparing outcomes of patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 to those with PS 0-1.Methods: Data were collected by 16 participating centres. All patients with NSCLC and high PD-L1, treated with first-line pembrolizumab were included. We collected medical data from patient files, pathology and laboratory reports. Patient characteristics, comorbidities, PS, and tumour characteristics were reported. Overall survival (OS), progression-free survival (PFS) and response rate (RR) were calculated.Results: 302 patients were included, 246 with PS 0-1, 56 with PS 2. RR was 72% among patients with PS 0-1 compared to 45% with PS2 (odds ratio (OR) 0.31 (95% CI: 0.17-0.57), p < .001). Median PFS was 2.6 months (95% CI: 1.9-5.1) among patients with PS2 and 11.3 months (95% CI: 8.5-14.4) among those with PS 0-1. Median OS was 7.8 months (95% CI: 2.5-10.7) in the PS2 group, not reached in the PS 0-1 group. PS 2 remained predictive of poor outcomes in multivariate analysis.Conclusion: PS 2 is a strong independent predictor of poor response and survival in NSCLC patients with high PD-L1, treated with front-line pembrolizumab. Prospective randomised trials comparing immunotherapy to chemotherapy in this population would be welcome.

Targeted Therapies in Early Stage NSCLC: Hype or Hope?

Non-small-cell lung cancer (NSCLC) represents roughly 85% of lung cancers, with an incidence that increases yearly across the world. The introduction in clinical practice of several new and more effective molecules has led to a consistent improvement in survival and quality of life in locally advanced and metastatic NSCLC. In particular, oncogenic drivers have indeed transformed the therapeutic algorithm for NSCLC. Nearly 25% of patients are diagnosed in an early stage when NSCLC is still amenable to radical surgery. In spite of this, five-year survival rates for fully resected early stage remains rather disappointing. Adjuvant chemotherapy has shown a modest survival benefit depending on the stage, but more than half of patients relapse. Given this need for improvement, over the last years different targeted therapies have been evaluated in early-stage NSCLC with no survival benefit in unselected patients. However, the identification of reliable predictive biomarkers to these agents in the metastatic setting, the design of molecularly-oriented studies, and the availability of novel potent and less toxic agents opened the way for a novel era in early stage NSCLC treatment. In this review, we will discuss the current landscape of targeted therapeutic options in early NSCLC.