Nivolumab is approved for the treatment of advanced non-small cell lung cancer (aNSCLC) after prior chemotherapy. The Lung Initiative on Sequence Therapy (LIST) study evaluated long-term outcomes, safety and feasibility of immunotherapy rechallenge in French patients with previously treated aNSCLC in routine practice. We report the results of the final 24-month analysis. LIST was a longitudinal, prospective, observational study enrolling patients with aNSCLC who had received ≥ 1 prior line of therapy and were initiating treatment with nivolumab. Patients were classified into three cohorts according to prior immunotherapy exposure: immunotherapy-naïve (cohort 1); immunotherapy-experienced and discontinued prior immunotherapy for reasons other than immunotherapy-related toxicity (cohort 2); and discontinued because of immunotherapy-related toxicity (cohort 3). The primary endpoint was time to treatment discontinuation (TTD). Secondary endpoints included overall survival (OS), progression-free survival (PFS), response at 24 months, safety and quality of life (QoL). A total of 522 patients were included (cohort 1, n = 280; cohort 2, n = 197; cohort 3, n = 45). Median TTD was 3.8, 3.2 and 3.4 months in cohorts 1, 2 and 3, respectively, with 24-month discontinuation-free rates of 7.9

Introduction:Extensive-stage SCLC (ES-SCLC) is a highly aggressive type of lung cancer with a high risk of early progression and limited survival. Standard of care for first-line treatment is platinum-etoposide chemotherapy plus anti-PD-L1 immune checkpoint inhibitors. Methods:Intergroupe Francophone de Cancérologie Thoracique-1905 CLINATEZO is a nationwide, non-interventional, retrospective study of consecutive patients with ES-SCLC who received atezolizumab plus platinum-based chemotherapy as part of the French Early Access Program that ran from May 2019 to March 2020. In this analysis, predictors of long-term response (defined by a real-world progression-free survival [rwPFS] > 12 mo) and long-term survival (defined by an overall survival [OS] > 24 mo) were assessed. Results:A total of 517 patients were enrolled from 65 centers. After a median follow-up of 53.8 months, median, 12-month, and 48-month rwPFS rates were 5.2 (95% confidence interval [CI]: 5.0-5.4) months, 14.6% (95% CI: 11.6-17.9), and 6.8% (95% CI: 4.7-9.4), respectively. Median, 24-month, and 48-month OS rates were 11.3 (95% CI: 10.1-12.4) months, 21.1% (95% CI: 17.7-24.8), and 11.4% (95% CI: 8.8-14.4), respectively.Long-term response was observed in 12.6% patients. Median OS was 9.7 months in patients with rwPFS less than or equal to 12 months and 53.7 months in patients with rwPFS more than 12 months. Baseline characteristics associated with rwPFS more than 12 months were being a former smoker (versus current smoker, p = 0.003) and having an Eastern Cooperative Oncology Group performance status of 0 to 1 (versus 2, p = 0.048).Long-term survival was observed in 20.5% patients. Median OS was 8.8 months in patients with OS less than or equal to 24 months and 52.9 months in patients with OS more than 24 months. Predictors of long-term survival were younger age (p = 0.030), limited stage at initial diagnosis of SCLC (p = 0.022), and previous line of platinum-based chemotherapy (p = 0.01). Conclusions:CLINATEZO demonstrates the reproducibility of the key survival outcomes of landmark trials, in a real-life setting, for patients with ES-SCLC. Only low smoking history and performance status were associated with long-term response in our cohort.

11107 Background: Remote symptom monitoring using electronic patient-reported outcome (ePRO) has been shown to provide clinical benefits and is being implemented for routine care in cancer patients (pts). It may represent a significant operational burden for healthcare providers, that has to be balanced with its actual efficiency in generating clinically meaningful alerts leading to modify pts management. Methods: REAL-MOOV-LUNG is a prospective, multicenter, phase IV trial evaluating the MOOVCARE system in patients (pts) ≥18yo with non-progressive lung cancer, any histology, any stage, who had completed anticancer treatment for < 8weeks (cohort 1), or who were receiving adjuvant, consolidation or maintenance anticancer treatment for ≥8weeks (cohort 2). Primary endpoint was the proportion of patients who had a clinically meaningful modification of the management, predefined as unplanned consultation at the hospital or CT-scan imaging following a MOOVCARE alert. Secondary endpoints included management of alerts, patients and healthcare providers satisfaction, observance, quality-of-life, and survival. Results: From October 2021 to October 2024, 188 pts were enrolled, including 107 men, 81 women, 155 pts with non-small cell lung cancer, 36 with other histologies; 36 pts had oncogene-addicted tumors; 70 pts had metastatic disease, 58 locally-advanced disease, and 60 had early-stage disease. 92% of pts filled at least 1 ePRO questionnaire, median number of questionnaires was 56/pts; 81% of pts had at least 1 alert, median number of alerts was 11, and total number of alerts was 2294. After a median follow-up of 23.9 mo, 39 (21%) pts had a modification of management between 2 scheduled visits, 29 (74%) of which related to preplanned visit, not to an alert; among the remaining 10 (26%) pts, only 5 (13%) pts had clinically meaningful modifications as per the predefined definition. 18-month overall survival was 79.6% [IC95% 73.6%-86.1%]. Conclusions: While adoption of remote symptom monitoring on ePRO was high, with frequent alerts generated from surveys, the actual impact on clinical management of patients with lung cancer was limited in the context of frequent preplanned visits at the hospital as per clinical guidelines. Clinical trial information: NCT04934865 .

Nivolumab is approved in France as monotherapy for the treatment of advanced (locally advanced or metastatic) non-small cell lung cancer (aNSCLC) after prior chemotherapy. The Lung Initiative on Sequence Therapy (LIST) study is evaluating the real-world effectiveness, safety and immunotherapy-rechallenge outcomes with nivolumab in previously treated French patients with aNSCLC. This longitudinal, prospective, observational study enrolled patients with aNSCLC who received ≥ 1 prior line of treatment that included chemotherapy. Three patient cohorts, based on prior treatment, were assessed: immunotherapy-naïve (cohort 1; prior chemotherapy, no prior immunotherapy), and immunotherapy-experienced, including patients who discontinued prior immunotherapy for reasons other than immunotherapy-related toxicity (cohort 2) and those who discontinued because of immunotherapy-related toxicity (cohort 3). The primary endpoint was time to treatment discontinuation (TTD). Results after at least 12 months of follow-up are reported. At data cut-off (September 2024), 522 patients were enrolled. In cohort 1 (N = 280), cohort 2 (N = 197) and cohort 3 (N = 45), the 12-month TTD rate was 17.7

BackgroundCOVID-19 started to spread early in 2020, the precise year that lung cancer (LC) patients were recruited into the prospective epidemiological cohort KBP-2020-CPHG in French hospitals. This provides a unique opportunity to study COVID-19 incidence, survival risk factors, and overall prognosis.MethodsCOVID data was collected before vaccination was made available. Clinical characteristics were compared (COVID vs non-COVID), incidence rate ratios were calculated based on clinical characteristics, survival (1 and 3 months) was estimated and the impact of COVID-19 on the overall prognosis of the cohort was studied.ResultsIn 2020, 285 out of 8,999 lung cancer patients were diagnosed with COVID-19. Diagnosis was mainly based on PCR tests (86.3%). The annual incidence was 8.3% (95% CI [7.4, 9.3]); it was higher in former smokers and patients with squamous cell carcinoma or small cell carcinoma than in those with adenocarcinoma, in those with a PS score ≥2 versus 0-1, and with stages III-IV versus stages I-II. The incidence was reduced in patients who received chemotherapy or immunotherapy. 64.9% of patients were hospitalized due to COVID-19. Risk factors for death at 1 and 3 months in COVID-19 patients were age, LC stage, and PS score. Multivariate analysis showed a major prognostic impact of COVID-19 on mortality of LC patients (hazard ratio: 4.12, 95% CI [3.42, 4.97], p < 0.001).ConclusionsThis prospective study demonstrated the high incidence of COVID-19 in LC patients and identified as risk factors for COVID-19: smoking status, histology, PS, and stage. The impact of COVID-19 on lung cancer mortality appears major.

8542 Background: Each decade since 2000, the French College of General Hospital Pulmonologists (CPHG) conducts the KBP study, a real-life nationwide prospective multicenter study on LC in non-academic public hospital (NPH). Here, we report the two-year survival (2-y) rate among the 2020 cohort and the comparisons with the 2000 and 2010 cohorts. Methods: Collection of all consecutive diagnosed LC, all stage and all histology, between 01/01 and 12/31 in NPH pulmonology or oncology units in 2000, 2010 and 2020 with the same methodology. A Scientific Committee controlled inclusion exhaustivity and quality in each center. Survival rates were calculated using the Kaplan-Meier method and risk factors were assessed using Cox models. Results: 8,999 patients were included in 82 centers in 2020. The 2-y survival rate was 40.3%, the median overall survival was 15.3 months. Compared to 2000, mortality rates at 2 years decreased significantly (-19.1%), while early (1 month and 3 months) mortality remains similar. Survival improved in 20 years whatever histologic types (Table). Factors associated with 2-y survival were sex (36.1% vs 48.1% respectively for male and female respectively, significantly increased over 20 years: + 15.3% for M and + 24.5% for F), high age (>80 y-o), poor ECOG status (3 or 4) and advanced disease. As expected in 2020, TNM stage was still determining for 2-year mortality, 15.2 [12.6-17.7] stage I vs 75.6 [74.4-76.8] stage IV. In 2020 the Covid-19 infection (n=283) impacted the survival (HR = 4.02 95%CI [3.33-4.86]) on multivariate analysis adjusted to age, sex, tobacco consumption, histology, ECOG status, TNM stage. Conclusions: These results confirmed the major improvement in the last two decades for LC. 5-years survival will provide us more enlightenment. [Table: see text]

8584 Background: Novel options are needed for pts with ES-SCLC after the failure of first-line chemotherapy. Lurbinectedin demonstrated efficacy in a landmark phase II study [Trigo et al. Lancet Oncol. 2020 May;21(5):645], and was granted EAP-ATU in France in June 2020. Methods: Multicenter, retrospective cohort of consecutive pts with histologically or cytologically confirmed ES-SCLC, who received at least one dose of treatment with lurbinectedin as part of the French EAP-ATU from June 2020 until March 2021, and gave consent for the data collection, were enrolled in 47 sites. Primary and secondary endpoints were description of clinical characteristics, and exposure to treatment, response, PFS, OS, safety. Results: 312 pts – 64% male, median age 65 years, 72% PS0-1, 47% with brain metastasis, 58% with previous immunotherapy – were enrolled. Lurbinectedin was administered as second-line in 44% of pts; 58% were chemotherapy-refractory. Pts received a median number of 3 cycles of lurbinectedin. Concurrent radiotherapy on metastases was delivered to 38% of pts. Lurbinectedin was discontinued because of progression/death/toxicity/other reasons in 83%/8%/5%/4% of pts. Grade3/4 events were observed in 9%/5% of pts. Response rate was 22% [95%CI 17-27%], disease control rate was 38% [95%CI 32-44%]. After a median follow-up of 20.8 months, median PFS and OS were 1.9 [95%CI 1.8-2] and 4.7 [95%CI 4-5.4] months; 6-month PFS and OS were 7% [4-10%] and 42% [95%CI 37-48%]. PS≤2 and chemotherapy-free interval≥90days were associated with significantly longer OS (HR = 0.71 [95%CI 0.53-0.95] and HR = 0.58 [95% CI 0.44-076] respectively). Main sites of progression were the lung (39% of pts), the brain (39% of pts), the liver (30% of pts), and the mediastinum (30% of pts). Subsequent treatment was administered to 154 pts after discontinuation of lurbinectedin, mostly consisting of topotecan (26% of pts); response/disease control rates, and median PFS of first subsequent treatment were 11% [95%CI 6-17%], 35% [95%CI 27-44%], and 1.9 [95%CI 1.7-2.3] months. Conclusions: Lurbinectedin provides an additional option from second-line for ES-SCLC, with efficacy outcomes comparable to that of historical treatments.

OBJECTIVES:Among interstitial pneumonia with autoimmune features (IPAF) patients, identifying those at risk to develop a connective tissue disease (CTD) during the disease course is a key issue. The aim of this study was to evaluate the incidence of definite CTD diagnosis in IPAF patients during follow-up. METHODS:We performed a multicentric cohort study of interstitial lung disease (ILD) from 2010 to 2017 in pneumology and immunology departments of tertiary care centers. Patients with a known cause of ILD (including established CTD) at diagnosis were excluded. Among patients with idiopathic ILD and at least three years of follow-up, two groups (IPAF and non-IPAF) were retrospectively analyzed at time of diagnosis. RESULTS:A total of 249 patients with ILD were enrolled, including 70 IPAF and 179 non-IPAF patients. After a mean follow-up time of 77 ± 44 months, 18/70 IPAF patients (26%) had a CTD diagnosis - 9 antisynthetase syndrome, 8 systemic sclerosis and 1 overlap myositis - compared with 4/179 non-IPAF patients (2%). IPAF patients were at higher risk of CTD occurrence at 3 years of follow-up compared to non-IPAF patients (HR 10.1, 95% CI 3.1-33.1, p < 0. 01). IPAF patients progressing to CTD tended to be younger, more often female and have more frequently puffy fingers, capillaroscopy abnormalities and antisynthetase antibodies at diagnosis. CONCLUSIONS:We found that a significant proportion of IPAF patients had associated CTD diagnosis during follow-up. Prospective studies are needed to confirm baseline predictive factors of CTD occurrence in IPAF patients.

Rationale: Idiopathic chronic obliterative bronchiolitis (OB) in adults is a very rare entity that has been little described. We aimed at evaluating the clinical, functional, radiological, and pathologic characteristics of patients with OB. Methods: After IRB approval, a retrospective cohort study was conducted in the OrphaLung Network in France. Patients with a histological confirmation or direct features of bronchiolitis at chest CT (peripheral micronodules, and/or branching infiltrates in V or Y shape) were considered eligible. Imaging eligibility criteria were confirmed by two experienced pulmonologists. Cases related to connective tissue disease, drugs, transplantation or other etiologies were excluded. Results: A total of 68 patients were included, with a median age of 55 years (18-72 years), and 70% of females. Only 26 patients had a history of smoking (mean 17 pack-years). The mean FVC was 76% ±21 of predicted. The mean FEV1 was 58% ±22%. The mean FEV1/FVC was 0.61(±0.17). DLco was 68% ±19% and Kco was 90% ±21%. Airflow obstruction was present despite bronchodilators in 47 patients (69%). Direct signs of bronchiolitis were present on CT in 55 patients (81%). Lung pathology available in 24 patients demonstrated follicular (7 cases), granulomatous (3), lymphocytic (8), and constrictive (6) bronchiolitis, respectively. The median duration of follow-up was 5 years (5-20 years). Outcome data will be presented. Conclusion: OB is a rare chronic condition associated with frequent persistent airflow obstruction, and various pathologic patterns. Typical CT features may be missing. Prospective studies are needed to evaluate the benefit of potential treatments.

OBJECTIVES:Cancer patients with pre-existing autoimmune disease, such as systemic sclerosis (SSc), are excluded from clinical trials, so the data on tolerability and efficacy of immune checkpoint inhibitors in these patients are limited. This study investigated the tolerability and efficacy of anti-programmed death ligand 1 (PD (L)1) immunotherapies in patients with pre-existing SSc. METHODS:Scleronco-01 was a multicentre, nationwide, open-label, phase IV observational study, from 2019 to 2021. RESULTS:Seventeen SSc patients receiving treatment for lung carcinoma (n = 13, 77%), head and neck cancer (n = 2, 12%), melanoma (n = 1, 6%), and colorectal carcinoma (n = 1, 6%) were included. The median (interquartile range) patient age was 60 (34-82) years. Fifteen (88%) patients received anti-PD1 (nivolumab and pembrolizumab) and two (12%) anti-PD-L1 (durvalumab). The median follow-up duration was 12 (range, 2-38) months. Four patients (24%) experienced flare-up of SSc symptoms. Ten patients (59%) developed an immune-related adverse event (grade I-II in 11 patients [65%], grade III-IV in one [6%]) without grade V. The overall response rate was 41% (7/17 patients). The median overall survival was 15.8 (95% confidence interval: 7.3 to not reached) months. CONCLUSION:Anti-PD1 or PD-L1 immunotherapies are suitable options for cancer patients with pre-existing SSc. Longer follow-up periods are required for long-term safety analyses.

We describe an overweight COVID-19 patient with respiratory distress preceded by anosmia/dysgeusia with no lung injury shown on CT, angio-CT or ventilation/perfusion scans. Orthopnoea and paradoxical abdominal respiration were identified. Phrenic paralysis, demonstrated by examination of patient breathing, and on x-ray while standing breathing in and out, explained the respiratory distress. This is a rare and previously undescribed neurological complication of COVID-19 infection caused by vagus nerve injury. LEARNING POINTS:Phrenic paralysis must be kept in mind as a rare neurological complication of COVID-19.Vagus nerve palsy is a neurological manifestation as anosmia and dysgeusia, that were already identified in the olfactory system of COVID-19 patients.

Background: Liver toxicity during immune checkpoint inhibitor treatment is mostly due to immune mediated hepatitis. Viral hepatitis, as well as auto-immune or metabolic hepatitis, are considered as exclusion criteria for ICI induced immune hepatitis diagnosis. However, considering the high prevalence of viral hepatitis B infection and the increasing prescription of immune checkpoint inhibitors, their use in patients with HBV chronic viral infection may be common, even more if patients are treated for hepatocellular carcinoma. Few clinical studies directly deal with the risk of HBV reactivation during ICI therapy and real-life data is currently based on five reported cases of HBV reactivation, one with fatal outcome. In this review, we summarize the current available clinical information about HBV reactivation risk during ICI treatment, its hypothetic mechanism, and propose practical recommendations about verifying and monitoring HBV status throughout the treatment. (c) 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Background Paraneoplastic syndromes (PNS) are autoimmune disorders specifically associated with cancer. There are few data on anti-PD-1 or anti-PD-L1 immunotherapy in patients with a PNS. Our objective was to describe the outcome for patients with a pre-existing or newly diagnosed PNS following the initiation of anti-PD-1 or anti-PD-L1 immunotherapy. Methods We included all adult patients (aged ≥18) treated with anti-PD-1 or anti-PD-L1 immunotherapy for a solid tumor, diagnosed with a PNS, and registered in French pharmacovigilance databases. Patients were allocated to cohorts 1 and 2 if the PNS had been diagnosed before vs. after the initiation of immunotherapy, respectively. Findings Of the 1304 adult patients screened between June 27th, 2014, and January 2nd, 2019, 32 (2.45%) had a PNS and were allocated to either cohort 1 ( n = 16) or cohort 2 ( n = 16). The median (range) age was 64 (45–88). The tumor types were non-small-cell lung cancer ( n = 15, 47%), melanoma ( n = 6, 19%), renal carcinoma ( n = 3, 9%), and other malignancies ( n = 8, 25%). Eleven (34%) patients presented with a neurologic PNS, nine (28%) had a rheumatologic PNS, eight (25%) had a connective tissue PNS, and four (13%) had other types of PNS. The highest severity grade for the PNS was 1–2 in 10 patients (31%) and ≥ 3 in 22 patients (69%). Four patients (13%) died as a result of the progression of a neurologic PNS (encephalitis in three cases, and Lambert-Eaton syndrome in one case). Following the initiation of immunotherapy, the PNS symptoms worsened in eight (50%) of the 16 patients in cohort 1. Interpretation Our results show that PNSs tend to be worsened or revealed by anti-PD-1 or anti-PD-L1 immunotherapy. Cases of paraneoplastic encephalitis are of notable concern, in view of their severity. When initiating immunotherapy, physicians should carefully monitor patients with a pre-existing PNS.

Background: Osteoporosis is common in cystic fibrosis (CF). Its physiopathology remains unclear. Objective: To determine the prevalence of low bone mineral density (BMD) in adults with CF and to look for possible factors associated with osteopenia/osteoporosis. Methods: A prospective cross sectional study was designed to evaluate bone health in patients at our adults CF center. Clinical data were collected (age, body mass index, medical history, genetic mutation and treatment), as usual laboratory data, abdominal abnormalities on ultrasound (hepatomegaly, splenomegaly, cirrhosis, portal hypertension), and lung function parameters. BMD was measured by dual-photon X-ray absorptiometry at lumbar spine, femoral upper extremity and femoral neck. Results: Thirty patients were included (56.7% men; mean age = 24.5 years ± 4.1). Either osteopenia or osteoporosis was found in 63.4% patients at least at one bone site. A personal history of skeleton’s fracture was found in 34.5% patients (but only 1 was a low energy fracture). Liver abnormalities on ultrasound were found in 36.7% patients (but none had cirrhosis). Low BMD at least at one site was more frequent among patients with liver abnormalities on ultrasound (p = 0.002), and among patients with bad respiratory function, defined by low mean FEV1 (p = 0.04), low mean SpO 2 (p = 0.02), and a tendency to low mean FVC (p = 0.09). A tendency for more infectious respiratory exacerbations (p = 0.08) was also observed in this group of patients. Conclusion: several mechanisms may contribute to the bone loss seen in patients with CF: liver disease, and respiratory insufficiency as well as systemic chronic inflammation may play a central role.

Desquamative interstitial pneumonia (DIP) is characterised by the accumulation of numerous pigmented macrophages within most of the distal airspace of the lung and, sometimes, the presence of giant cells. Diagnosis of DIP is not easy and requires surgical lung biopsy. DIP is usually associated with tobacco smoke. However, the association between smoking and DIP is less robust than that with respiratory bronchiolitis with interstitial lung disease or pulmonary Langerhans' cell histiocytosis; approximately 10-42% of patients with DIP are nonsmokers. DIP can also occur in patients following exposure to certain inhaled toxins (occupational exposure) and drugs, and may occur in the context of certain viral illnesses and autoimmune diseases. In the context of DIP, occupational exposure should be systematically investigated.

To the Editor: Pulmonary ossification is a rare disease characterised by the formation of diffuse small fragments of mature bone tissue in the lungs. It can be idiopathic or associated with underlying chronic lung, heart or systemic disorders. We present the case of an 83-year-old male, who had diffuse dendriform pulmonary ossification (DPO) and a spontaneous pneumothorax. An 83-year-old male nonsmoker with a history of hypertension and carotid and coronary angioplasties visited his medical practitioner for right chest pain after a flight from Spain to France. He had no history of lung disease or heart failure. He worked as a dentist with a dental prosthesis manufacturer. Our patient was frequently in the same workshop as the prostheses technician. The patient had no trauma, cough, sputum disorders or dyspnoea. A physical examination and the usual biological analyses were normal, particularly the phosphocalcic values. Chest radiography revealed a partial right pneumothorax with micronodular calcified opacities in both lungs. Computed tomography revealed the presence of bilateral disseminated micronodular opacities of calcified densities, predominantly located in the lower lung, which had lower densities than silicosis. There were no calcified lymph nodes in the mediastinum (figs 1 and 2). Figure 1. a) Computed tomography (CT) of the chest in a parenchymal window demonstrating a right pneumothorax and a nodular round shadow in the collapsed lung; b) CT of the chest in …

PURPOSE:Increased hepatocyte growth factor/MET signaling is associated with poor prognosis and acquired resistance to epidermal growth factor receptor (EGFR) -targeted drugs in patients with non-small-cell lung cancer (NSCLC). We investigated whether dual inhibition of MET/EGFR results in clinical benefit in patients with NSCLC. PATIENTS AND METHODS:Patients with recurrent NSCLC were randomly assigned at a ratio of one to one to receive onartuzumab plus erlotinib or placebo plus erlotinib; crossover was allowed at progression. Tumor tissue was required to assess MET status by immunohistochemistry (IHC). Coprimary end points were progression-free survival (PFS) in the intent-to-treat (ITT) and MET-positive (MET IHC diagnostic positive) populations; additional end points included overall survival (OS), objective response rate, and safety. RESULTS:There was no improvement in PFS or OS in the ITT population (n = 137; PFS hazard ratio [HR], 1.09; P = .69; OS HR, 0.80; P = .34). MET-positive patients (n = 66) treated with erlotinib plus onartuzumab showed improvement in both PFS (HR, .53; P = .04) and OS (HR, .37; P = .002). Conversely, clinical outcomes were worse in MET-negative patients treated with onartuzumab plus erlotinib (n = 62; PFS HR, 1.82; P = .05; OS HR, 1.78; P = .16). MET-positive control patients had worse outcomes versus MET-negative control patients (n = 62; PFS HR, 1.71; P = .06; OS HR, 2.61; P = .004). Incidence of peripheral edema was increased in onartuzumab-treated patients. CONCLUSION:Onartuzumab plus erlotinib was associated with improved PFS and OS in the MET-positive population. These results combined with the worse outcomes observed in MET-negative patients treated with onartuzumab highlight the importance of diagnostic testing in drug development.