First-line single-agent pembrolizumab for PD-L1-positive (tumor proportion score ≥ 50%) advanced non-small cell lung cancer in the real world: impact in brain metastasis: a national French multicentric cohort (ESCKEYP GFPC study).

BACKGROUND: Few real-world data are available in patients with advanced metastatic non-small cell lung cancer (NSCLC) treated with first-line immunotherapy, particularly in those with brain metastases at treatment initiation. METHODS: This was a national, retrospective, multicenter study that consecutively included all patients with PD-L1-positive (tumor proportion score ≥ 50%) advanced NSCLC who initiated first-line treatment with pembrolizumab as a single agent between May 2017 (date of availability of pembrolizumab in this indication in France) to November 22, 2019 (approval of the pembrolizumab-chemotherapy combination). Data were collected from medical records with local response assessment. RESULTS: The cohort included 845 patients and 176 (20.8%) had brain metastases at diagnosis. There were no significant differences in outcomes for patients with and without brain metastases: 9.2 (95% CI 5.6-15) and 8 (95% CI 6.7-9.2, p = 0.3) months for median progression-free survival (PFS) and, 29.5 (95% CI 17.2-NA) and 22 (95% CI 17.8-27.1, p = 0.3) months for median overall survival (OS), respectively. Overall response rates were 47% and 45% in patients with and without cerebral metastases. In multivariate analysis, performance status 2-4 vs. 0-1 and neutrophil-to-lymphocyte ratio ≥ 4 vs. < 4 were the main independent negative factors for OS; brain metastasis was not an independent factor for OS. CONCLUSION: In this large multicenter cohort, nearly 20% of patients initiating pembrolizumab therapy for advanced NSCLC had cerebral metastases. There was no significant difference in response rates, PFS and OS between patients with and without brain metastases.

Immune checkpoint inhibitors in patients aged 80 or older with advanced non-small cell lung cancer or melanoma: a real-life multicentre study.

BACKGROUND: Data regarding characteristics, safety and survival outcomes of patients aged 80 or older treated with immune checkpoint inhibitors (ICI) in routine oncology practice are limited. MATERIALS AND METHODS: We retrospectively collected data of patients aged 80 and older with advanced non-small cell lung cancer (NSCLC) or melanoma treated with anti-PD1, anti-PD-L1 or anti-CTLA-4 regardless of the treatment line, in 14 institutions, between January 2014 and June 2017. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan Meier method. Toxicity was assessed according to CTCAE 5.0. Multivariate analyses were performed with the Cox model. RESULTS: Eighty-two patients were included (36 with NSCLC, 45 with melanoma). Their median age was 82 years (range 80-93). Nivolumab and pembrolizumab were mainly used. In the NSCLC group, median PFS and OS were 2.3 months (95%CI 1.8-6.1) and 8.8 months (95%CI 5.5-18.1), respectively. In the melanoma group, median PFS and OS were 10.2 months (95%CI 4.5-20.0) and 24.5 months (95%CI 14.1-NR), respectively. The albumin level was found to be independently associated with a better OS in both groups. Grade 3-4 toxicities occurred in 15 patients (18.5%). One patient died from ICI-induced pulmonary toxicity. CONCLUSION: Our study findings suggest that treatment with ICI in elderly patients with NSCLC and melanoma has a risk-benefit ratio that supports its use. However, we report in this cohort that one in five patients has a grade 3-4 IRAEs leading to treatment discontinuation. Geriatric assessment prior to initiation of therapy and during therapy should be routine in patients aged 80 years and older.

The illusion of a chest wall tumor: a case-report of sternal tuberculosis.

The incidence rate of tuberculosis in developed countries is low. The most common presentation of this disease is its pulmonary form but with the increasing use of immunosuppressive drugs, extra-pulmonary tuberculosis is re-emerging. Nevertheless, sternal bone involvement is uncommon. We report the case of an eighty-three-year-old man who presented a painful sternal mass which progressed towards cutaneous ulceration. The first diagnostic hypothesis was neoplasia. The pathological and microbiological diagnosis of tuberculosis was achieved after surgical biopsy. The patient received treatment against tuberculosis for nine months enabling recovery without surgery. This case illustrates the importance of having a diagnosis prior to any kind of treatment facing any voluminous parietal thoracic lesions.  This diagnosis is made possible by surgical samples and interdisciplinary teamwork. This case underlines that tuberculosis remains a differential diagnosis that must be evoked in case of unusual bone mass.

First-line pembrolizumab with or without platinum doublet chemotherapy in non-small-cell lung cancer patients with PD-L1 expression ≥50.

Pembrolizumab plus chemotherapy is currently used in the first-line treatment of advanced non-small-cell lung cancer without EGFR mutations or ALK rearrangements, regardless of PD-L1 expression status. A study comparing chemotherapy plus pembrolizumab versus pembrolizumab alone has never been performed in patients with PD-L1 ≥50%. The aim of this trial is to perform such a comparison as first-line treatment in patients not eligible for locally advanced treatment who have expression of PD-L1 on ≥50% of tumor cells. The expected results are a reduction in the risk of early progression. A higher objective tumor response is also expected with the combination of chemotherapy and pembrolizumab compared with pembrolizumab alone. The study will allow a direct comparison of the proportion of patients who derive long-term benefit from the treatment. Clinical trial number: EudraCT (2020-002626-86); ClinicalTrials.gov (NCT04547504).

Lay abstract Non-small-cell lung cancer (NSCLC) is the most frequent type of lung cancer. Most NSCLC patients are diagnosed with advanced disease and only 10­15% of them are alive after 5 years. In the absence of specific tumor mutations, the currently recommended treatment is a combination of chemotherapy and immunotherapy with the monoclonal antibody pembrolizumab. The goal of immunotherapy is to prevent cancer from evading the immune system by interacting with molecules expressed at the surface of tumor cells (PD-L1) or immune cells (PD-1). A study comparing chemotherapy plus pembrolizumab versus pembrolizumab alone has never been performed in patients with a high level of PD-L1 expression on tumor cells. Therefore we designed the PERSEE study to compare these treatments in advanced-stage NSCLC patients with PD-L1 expression on ≥50% of tumor cells.

Determination of amoxicillin and cotrimoxazole concentrations in sputum of patients with cystic fibrosis.

In the management of cystic fibrosis, treatments against Staphylococcus aureus and Haemophilus influenzae such as amoxicillin or cotrimoxazole have to be prescribed and the antibiotherapy's efficacy may be linked to the concentration that reaches the infected site. As cystic fibrosis patients present disturbed pharmacokinetics parameters, drug monitoring would be relevant to assess the lung distribution of antibiotics and to optimize dosing regimens. In this context, the aim of the study was to develop and validate HPLC-based methods for the determination of both antibiotics in bronchial sputum from cystic fibrosis patients, in order to assess the distribution of the drugs into the lungs. Plasma proteins were precipitated by acetonitrile and amoxicillin concentrations in sputum were determined by HPLC coupled with tandem-mass spectrometry. Following liquid extraction with ethyl acetate, cotrimoxazole was quantified by HPLC using ultraviolet detection. Both methods were rapid, specific, accurate and reproducible. The method was applied to patient samples. In three treated patients, concentrations of amoxicillin in sputum were similar and below the lower limit of quantification (0.1 µg/g) and in six patients, sputum concentrations up to 11.1 and 6.4 µg/g were measured for sulfamethoxazole and trimethoprim, respectively.

Thoracic splenosis: Case report of a symptomatic case.

Thoracic splenosis is the autotransplantation of splenic tissue in the left thoracic cavity as a result of a splenic injury. This rare pathology is usually asymptomatic and may be discovered on incidental imaging, but the diagnosis often requires invasive procedures such as surgery in order to eliminate a neoplasic origin. We report a rare symptomatic case of a 39-year-old man presenting with chest pain and multiple nodules revealed on a computed tomography scan. The patient underwent a surgical exploration and the pathological studies concluded to a thoracic splenosis. Indeed, the previous medical history of the patient revealed a left thoraco-abdominal traumatism during childhood. The aim of this paper is to emphasize that the diagnosis can now be performed using only imaging techniques such as technetium-99 sulfur colloid or labelled heat-denatured red blood cell scintigraphy to avoid unnecessary invasive procedures including thoracotomy.

Human ex vivo prostate tissue model system identifies ING3 as an oncoprotein.

BACKGROUND: Although the founding members of the INhibitor of Growth (ING) family of histone mark readers, ING1 and ING2, were defined as tumour suppressors in animal models, the role of other ING proteins in cellular proliferation and cancer progression is unclear. METHODS: We transduced ex vivo benign prostate hyperplasia tissues with inducible lentiviral particles to express ING proteins. Proliferation was assessed by H3S10phos immunohistochemistry (IHC). The expression of ING3 was assessed by IHC on a human prostate cancer tissue microarray (TMA). Gene expression was measured by DNA microarray and validated by real-time qPCR. RESULTS: We found that ING3 stimulates cellular proliferation in ex vivo tissues, suggesting that ING3 could be oncogenic. Indeed, ING3 overexpression transformed normal human dermal fibroblasts. We observed elevated levels of ING3 in prostate cancer samples, which correlated with poorer patient survival. Consistent with an oncogenic role, gene-silencing experiments revealed that ING3 is required for the proliferation of breast, ovarian, and prostate cancer cells. Finally, ING3 controls the expression of an intricate network of cell cycle genes by associating with chromatin modifiers and the H3K4me3 mark at transcriptional start sites. CONCLUSIONS: Our investigations create a shift in the prevailing view that ING proteins are tumour suppressors and redefine ING3 as an oncoprotein.

Ambulatory management of large spontaneous pneumothorax with pigtail catheters.

STUDY OBJECTIVE: There is no consensus about the management of large spontaneous pneumothoraces. Guidelines recommend either needle aspiration or chest tube drainage and most patients are hospitalized. We assess the efficiency of ambulatory management of large spontaneous pneumothoraces with pigtail catheters. METHODS: From February 2007 to January 2011, all primary and secondary large spontaneous pneumothoraces from Lorient's hospital (France) were managed with pigtail catheters with a 1-way valve. The patients were discharged immediately and then evaluated every 2 days according to a specific algorithm. RESULTS: Of the 132 consecutive patients (110 primary, 22 secondary), 103 were exclusively managed as outpatients, with full resolution of the pneumothorax by day 2 or 4, which represents an ambulatory success rate of 78%. Mean time (SD) of drainage was 3.4 days (1.8). Seven patients were initially hospitalized but quickly discharged and had full resolution by day 2 or 4, leading to a total success rate of 83%. The use of analgesics was low. The 1-year recurrence rate was 26%. If successful, this outpatient management is potentially cost saving, with a mean cost of $926, assuming up to 2 outpatient visits and 1 chest radiograph, compared with $4,276 if a chest tube was placed and the patient was admitted to the hospital for 4 days. CONCLUSION: Ambulatory management with pigtail catheters with 1-way valves could be a reasonable first-line of treatment for large spontaneous pneumothoraces. Compared with that of other studies, our protocol does not require hospitalization and is cost saving.

[Incidence, characteristics and survival of patients with pneumocystis pneumonia in solid oncology]. / Incidence, caractéristiques et survie des patients présentant une pneumocystose en oncologie solide.

INTRODUCTION: Pulmonary pneumocystis causes interstitial lung disease, particularly in patients with solid cancers. The aim of this study is to clarify its incidence, which remains poorly understood, and to identify patients at risk and prognostic factors. METHODS: Data on patients with solid tumors and pulmonary pneumocystis were retrospectively collected from January 1, 2014 to December 31, 2019 in two hospitals in Rennes. Incidence was estimated via the Poisson model. Survival data were estimated using Kaplan-Meier method and Log-rank test. A multivariate Cox model was performed to identify risk factors for death. RESULTS: The incidences of pulmonary pneumocystis in metastatic cancer patients receiving parenteral systemic therapy are 198 and 349 cases per 100,000 patients per year in these two centers, respectively. Most patients were being treated with corticosteroids and chemotherapy at the time of pulmonary pneumocystis. The mortality rate for patients with pulmonary pneumocystis is 38%. Median overall survival was 2,7 months. Risk factors for death are corticotherapy greater than 20mg, prednisone equivalent, daily and chemotherapy. DISCUSSION: Pulmonary pneumocystis pneumonia is rare but not exceptional and has a poor prognosis in solid oncology. It frequently occurs in patients treated with long-term corticosteroids. Oncologists need to be better informed to discuss prophylaxis whenever corticosteroids are prescribed for several weeks.

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.

Afatinib or Bevacizumab in combination with Osimertinib efficiently control tumor development in orthotopic murine models of non-small lung cancer.

Lung cancer is one of the most common and deadliest cancers. Preclinical models are essential to study new therapies and combinations taking tumor genetics into account. We have established cell lines expressing the luciferase gene from lines with varied genetic backgrounds, commonly encountered in patients with pulmonary adenocarcinoma. We have characterized these lines by testing their response to multiple drugs. Thus, we have developed orthotopic preclinical mouse models of NSCLC with very high engraftment efficiency. These models allow the easy monitoring of tumor growth, particularly in response to treatment, and of tumor cells dissemination in the body. We show that concomitant treatment with osimertinib (3rd generation tyrosine kinase inhibitor targeting mutated EGFR) and bevacizumab (anti-angiogenic targeting VEGF) can have a beneficial therapeutic effect on EGFR-mutated tumors. We also show that the addition of afatinib to osimertinib-treated tumors in escape leads to tumor growth inhibition. No such effect is observed with selumetinib or simvastatin. These preclinical mouse models therefore make it possible to test innovative therapeutic combinations and are also a tool of choice for studying resistance mechanisms.

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.

A prospective analysis of the management practices for patients with Stage-III-N2Non-Small-Cell lung cancer (OBSERVE IIIA-B GFPC 04-2020Study).

BACKGROUND: Management of stage-III-N2 non-small-cell lung cancer (NSCLC) based on a multimodal strategy (surgery or radiotherapycombined with systemic drugs) remains controversial. Patients are treated with a curative intent, and available data suggestprolonged survival after complete resection. However, no consensual definition of "tumor resectability" exists. This study aimed to analyze the concordanceamong French tumor board meeting (TBM)-emittedtherapeutic decisions forstage-III-N2 NSCLC. METHODS: Six patients with stage-III-N2 NSCLC discussed at Saint-Etienne University Hospital'sthoracic TBMs were selected, anonymouslyreported, and submitted to the participating TBMs. The primary goal of this multicenter, prospective, observational study was to assess the consistency of TBMpanel decisions for each case. The secondary endpointwas identifying the demographic or technical factors that potentiallyaffected decision-making. RESULTS: Twenty-seven TBMs from university hospitals, a cancer center, general hospitals, and a private hospitalparticipated in this study. None of their decisions for the six cases were unanimous.The decisions were homogenous for three cases (78%, 85%, and 88% TBMs opted for medical treatment, respectively),andmore ambivalent for the other three (medical versus surgical strategies were favored by 44%/56%, 46%/54%, and 58%/42% TBMs, respectively). Interestingly, decisions regarding chemoradiationand perioperative chemotherapyinthe medical and surgical strategies, respectively, were also discordant. Hospital type, specialist participation in TBMs, and activity volumes were not significantly associated with therapeutic decisions. CONCLUSION: The results of this study highlight substantial disparities amongFrench TBMs regarding therapeutic management of stage-III-N2 NSCLC. The decisions were not associated with local conditions.

Newly identified tumor suppressor functions of ING proteins.

The INhibitor of Growth (ING) proteins (ING1, ING2, ING3, ING4 and ING5) are a family of epigenetic regulators. Their decreased expression in numerous cancers led to identifying the ING proteins as gatekeeper tumor suppressors as they regulate cell cycle progression, apoptosis and senescence. Subsequently, they were also described as caretaker tumor suppressors through their involvement in DNA replication and the DNA damage response (DDR). Recent studies have identified new interactions of the ING proteins with proteins or pathways implicated in cell proliferation, the maintenance of stem cells pluripotency or the DDR. Furthermore, the ING proteins have been identified as regulators of ribosomal RNA synthesis and of mRNA stability and as regulators of mitochondrial DNA transcription resulting in the regulation of metabolism. These new findings highlight new antitumorigenic activities of the ING proteins that are potential targets for cancer treatment.

Safety and efficacy of second-line metronomic oral vinorelbine-atezolizumab combination in stage IV non-small-cell lung cancer: An open-label phase II trial (VinMetAtezo).

OBJECTIVE: To evaluate the safety and efficacy of second-line metronomic oral vinorelbine-atezolizumab combination for stage IV non-small-cell lung cancer. METHODS: This was a multicenter, open-label, single-arm Phase II study performed in patients with advanced NSCLC without activating EGFR mutation or ALK rearrangement who progressed after first-line platinum-doublet chemotherapy. Combination treatment was atezolizumab (1200 mg IV day 1, every 3 weeks) and oral vinorelbine (40 mg, 3 times by week). The primary outcome was progression-free survival (PFS) during the 4-month follow-up from the first dose of treatment. Statistical analysis was based on the exact single-stage Phase II design defined by A'Hern. Based on literature data, the Phase III trial threshold was set at 36 successes in 71 patients. RESULTS: 71 patients were analyzed (median age, 64 years; male, 66.2%; ex-smokers/active smokers, 85.9%; ECOG performance status 0-1, 90.2%; non-squamous NSCLC, 83.1%; PD-L1 ≥ 50%, 4.4%). After a median follow-up of 8.1 months from treatment initiation, 4-month PFS rate was 32% (95% CI, 22-44), i.e. 23 successes out 71 patients. OS rate was 73.2% at 4 months and 24.3% at 24 months. Median PFS and OS were 2.2 (95% CI, 1.5-3.0) months and 7.9 (95% CI, 4.8-11.4) months, respectively. Overall response rate and disease control rate at 4 months were 11% (95% CI, 5-21) and 32% (95% CI, 22-44), respectively. No safety signal was evidenced. CONCLUSION: Metronomic oral vinorelbine-atezolizumab in the second-line setting did not achieve the predefined PFS threshold. No new safety signal was reported for vinorelbine-atezolizumab combination.

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.

Predictors of three-month mortality and severe chemotherapy-related adverse events in patients aged 70 years and older with metastatic non-small-cell lung cancer: A secondary analysis of ESOGIA-GFPC-GECP 08-02 study.

INTRODUCTION: Predictors for mortality and toxicity in older patients with cancer are mainly studied in cohorts with various cancers at different stages. This study aims to identify predictive geriatric factors (PGFs) for early death and severe chemotherapy related adverse events (CRAEs) in patients aged ≥70 years with metastatic non-small-cell lung cancer (mNSCLC). MATERIAL AND METHODS: This is a secondary analysis of the multicenter, randomized, phase 3 ESOGIA trial that compared, for patients ≥70 years with mNSCLC, a treatment algorithm based on performance status and age to another algorithm based on geriatric assessment. To identify PGFs of three-month mortality and grade 3, 4, or 5 CRAEs, multivariate Cox models and logistic models, adjusted for treatment group and center, and stratified by randomization arm, were constructed. RESULTS: Among 494 included patients, 145 (29.4%) had died at three months and 344 (69.6%) had severe chemotherapy toxicity. For three-month mortality, multivariate analyses retained mobility (Test Get up and Go), instrumental activity of daily living (IADL) dependence and weight loss as PGFs. The combined effect of IADL ≤2/4 and weight loss ≥3 kg was strongly associated with three-month mortality (adjusted hazard ratio: 5.71 [95% confidence interval [CI]: 2.64-12.32]). For chemotherapy toxicity, Charlson Comorbidity Index ≥2 was independently associated with grade3, 4, or 5 CRAEs (adjusted odds ratio [95% CI]: 1.94 [1.06-3.56]). DISCUSSION: Mobility, IADL dependence, and weight loss were predictive of three-month mortality in a population aged ≥70 years treated for mNSCLC, while comorbidities were independently associated with severe chemotherapy toxicity.

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29).

Background: Pembrolizumab combined with chemotherapy is now first-line standard of care in advanced non-small cell lung cancer. This real-life study aimed to assess efficacy and safety of carboplatin-pemetrexed plus pembrolizumab in advanced non-squamous non-small cell lung cancer. Methods: CAP29 is a retrospective, observational, multicenter real-life study conducted in 6 French centers. We evaluated efficacy of first-line setting chemotherapy plus pembrolizumab (November 2019 to September 2020) in advanced (stage III-IV) non-squamous non-small cell lung cancer patients without targetable alterations. Primary endpoint was progression-free survival. Secondary endpoints were overall survival, objective response rate and safety. Results: With a median follow-up of 4.5 months (0 to 22 months), a total of 121 patients were included. Baseline characteristics were: median age of 59.8 years with 7.4% ≥75 years, 58.7% of males, 91.8% PS 0-1, 87.6% of stage IV with ≥3 metastatic sites in 62% of cases. Patients had brain and liver metastases in 24% and 15.7% of cases, respectively. PD-L1 was <1% (44.6%), 1-49% (28.1%) and ≥50% (21.5%). Median progression-free survival and overall survival achieved 9 and 20.6 months, respectively. Objective response rate was 63.7% with 7 prolonged complete responses. Survival benefit seemed to be correlated with PD-L1 expression. Brain and liver metastases were not statistically associated with decreased overall survival. Most common adverse events were asthenia (76%), anemia (61.2%), nausea (53.7%), decreased appetite (37.2%) and liver cytolysis (34.7%). Renal and hepatic disorders were the main causes of pemetrexed discontinuation. Grade 3-4 adverse events concerned 17.5% of patients. Two treatment-related deaths were reported. Conclusions: First-line pembrolizumab plus chemotherapy confirmed real-life efficacy for patients with advanced non-squamous non-small cell lung cancer. With median progression-free survival and overall survival of 9.0 and 20.6 months, respectively and no new safety signal, our real-life data are very close to results provided by clinical trials, confirming the benefit and the manageable toxicity profile of this combination.