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 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.
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.
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.
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.
BackgroundParaneoplastic 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.MethodsWe 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.FindingsOf 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.InterpretationOur 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.
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.
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.
Hepatitis B reactivation and immune check point inhibitors Godbert, Benoit; Petitpain, Nadine; Lopez, Anthony ...
Digestive and Liver Disease/Digestive and liver disease,
April 2021, 2021-04-00, 20210401, 2021-04, Letnik:
53, Številka:
4
Journal Article
Recenzirano
Odprti dostop
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.
•The incidence of COVID-19 was higher in former smokers, specific histological subgroups, PS score ≥2 vs 0- and in stages III-IV vs I-II patients.•In our cohort, the incidence COVID-19 was lower in ...active smokers, compared to former smokers and the chemotherapy had no impact.•In 2020, COVID-19 had a major impact on mortality of LC patients with the risk of death being more than four times that of the population non-COVID-19.
COVID-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.
COVID 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.
In 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).
This 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.
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.
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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
Bacteriophages have been shown to be effective for treating acute infections of the respiratory tract caused by antibiotic-resistant bacteria in animal models, but no evidence has yet been presented ...of their activity against pathogens in complex biological samples from chronically infected patients. We assessed the efficacy of a cocktail of ten bacteriophages infecting Pseudomonas aeruginosa following its addition to 58 sputum samples from cystic fibrosis (CF) patients collected at three different hospitals. Ten samples that did not contain P. aeruginosa were not analysed further. In the remaining 48 samples, the addition of bacteriophages led to a significant decrease in the levels of P. aeruginosa strains, as shown by comparison with controls, taking two variables (time and bacteriophages) into account (p = 0.024). In 45.8% of these samples, this decrease was accompanied by an increase in the number of bacteriophages. We also tested each of the ten bacteriophages individually against 20 colonies from each of these 48 samples and detected bacteriophage-susceptible bacteria in 64.6% of the samples. An analysis of the clinical data revealed no correlation between patient age, sex, duration of P. aeruginosa colonization, antibiotic treatment, FEV1 (forced expiratory volume in the first second) and the efficacy of bacteriophages. The demonstration that bacteriophages infect their bacterial hosts in the sputum environment, regardless of the clinical characteristics of the patients, represents a major step towards the development of bacteriophage therapy to treat chronic lung infections.
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