Invasive pulmonary aspergillosis (IPA) is a common cause of fungal infection acquired in intensive care unit (ICU) whose clinical landscape may differ according to SARS-CoV2 infection status. We included all mechanically ventilated patients hospitalized (≥ 48 h) participating in ICU of the REA-REZO network during a 6-year period. Among IPA patients, initial characteristics and outcomes were compared according to COVID-19. Additionally, to account for potential confounders, we performed an inverse probability of treatment weighting (IPTW). Rates of IPA were also compared according to SARS-CoV2 infection. Finally, we investigated risk factors associated with mortality among IPA patients using a Cox model regression. Among 120 993 patients included during the study period, IPA was diagnosed in 254 patients. COVID-19 Associated Pulmonary Aspergillosis (CAPA) patients were significantly older (median age 69 [62–73] years versus 63 [56–70] years; p < 0.001), less immunosuppressed (23.5
INTRODUCTION:The KBP-CPHG observational studies, conducted every 10 years, have shown a significant increase in the proportion of women with lung cancer, rising from 16.0 % in 2000 to 34.6 % in 2020 (P < 0.0001). We report differences in clinical, tumor, and prognostic characteristics between women and men. METHODS:All patients with primary lung cancer diagnosed in 2020 across 81 French centers were included. Patient and tumor characteristics were compared by sex. Patients in the KBP-2020 cohort were also compared with those from the 2000 and 2010 cohorts. RESULTS:The KBP-2020 study included 3,095 women and 5,846 men. Smoking was more frequent in men (93.6 %) than in women (75.7 %). Women were diagnosed at a younger age (median 66.8 vs 68.6 years; P < 0.0001) and had slightly better performance status (0-1: 76.2 % vs 73.7 %; P < 0.001). Adenocarcinoma predominated in both sexes but was more frequent in women (65.5 % vs 51.0 %; P < 0.0001). Molecular testing was performed more often in women (64.5 % vs 52.3 %; P < 0.0001) and identified more genetic alterations (58.2 % vs 42.1 %; P < 0.0001). Among stage IV adenocarcinoma cases, EGFR mutations were more frequent in women (27.5 % vs 7.9 %; P < 0.001). Women had better overall survival than men (4-year OS: 34.7 % vs 23.7 %; median OS: 21.9 vs 12.6 months; P < 0.0001). Female sex was associated with improved survival in multivariable analysis (HR 0.79; 95 % CI 0.74-0.84; P < 0.0001). This association was no longer significant in a stage IV NSCLC-restricted model including an interaction with first-line treatment (HR 0.88; 95 % CI 0.77-1.02; P = 0.087). CONCLUSION:Women with lung cancer had better survival than men, but this advantage was no longer significant after adjustment for treatment differences.
BACKGROUND:Patients with unresectable hepatocellular carcinoma have a poor prognosis and treatments with long-term benefits are needed. Anti-PD-L1 or anti-PD-1 plus anti-VEGF or anti-CTLA-4 double combinations are validated, first-line, systemic immunotherapies. We report the preplanned phase 2 results of the phase 2-3 PRODIGE 81-FFCD 2101-TRIPLET-HCC trial investigating the survival outcomes and safety profile of a triple combination of atezolizumab, bevacizumab, and ipilimumab in a first-line setting. METHODS:This randomised, open-label, phase 2-3 trial enrolled patients aged 18 years or older with unresectable hepatocellular carcinoma without previous systemic therapy at 36 hospitals in France. Patients had at least one measurable untreated lesion per Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1), Child-Pugh class A disease, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned (1:1) to receive intravenous treatment every 3 weeks for up to 2 years with atezolizumab 1200 mg plus bevacizumab 15 mg/kg (plus ipilimumab 1 mg/kg for up to four doses), or atezolizumab plus bevacizumab alone. Subsequent follow-up was for a further 2 years. Randomisation was done centrally by the study funder, via an electronic case report form, using the minimisation method, and stratified by centre, ECOG performance status, macrovascular invasion or extrahepatic spread (or both), and baseline α-fetoprotein. We report the non-comparative phase 2 results with a primary endpoint of objective response (complete or partial) within the first 24 weeks of treatment, assessed per investigator by RECIST v1.1, in patients who received at least the first dose of study medication (modified intention-to-treat population); 35 patients in the experimental group needed to have had an objective response at week 24 for the trial to progress to phase 3. Missing data were not replaced. The trial is registered with ClinicalTrials.gov (NCT05665348) and is complete. FINDINGS:Between March 9, 2023, and Sept 20, 2024, 229 patients were randomly assigned to treatment and 226 received at least one dose of study medication; 113 patients received atezolizumab plus bevacizumab plus ipilimumab and 113 received atezolizumab plus bevacizumab. 206 (91%) patients were male and 20 (9%) were female. At 24 weeks, 34 (30% [80% CI 24-36]) patients in the atezolizumab plus bevacizumab plus ipilimumab group had an objective response as had 31 (27% [22-34]) patients in the atezolizumab plus bevacizumab group. The trial was therefore stopped and did not progress to phase 3. The most common (>2% of patients) investigator-assessed treatment-related, grade 3-4 adverse events in the atezolizumab plus bevacizumab plus ipilimumab group were colitis (four [4%] patients), confusional syndrome (three [3%]), arterial hypertension (11 [10%]), and asthenia (six [5%]); the most common in the atezolizumab plus bevacizumab group were acute renal failure (three [3%] patients), proteinuria (four [4%]), gastrointestinal bleeding (six [5%]), arterial hypertension (13 [12%]), increased aspartate aminotransferase (three [3%]), increased alanine aminotransferase (three [3%]), and increased lipasaemia (three [3%]). Serious adverse events were reported in 55 (49%) patients in the atezolizumab plus bevacizumab plus ipilimumab group and in 48 (42%) patients in the atezolizumab plus bevacizumab group. Treatment-related adverse events resulting in death occurred in six (5%) patients in the atezolizumab plus bevacizumab plus ipilimumab group and none in the atezolizumab plus bevacizumab group. INTERPRETATION:The addition of ipilimumab to atezolizumab plus bevacizumab did not show any benefit in patients with previously untreated, unresectable hepatocellular carcinoma. These results do not support the addition of low-dose (1 mg/kg) ipilimumab to atezolizumab plus bevacizumab as a first-line treatment in this setting. FUNDING:Fédération Francophone de Cancérologie Digestive.
BACKGROUND:Small bowel adenocarcinoma (SBA) is a rare malignancy with poor prognosis. In metastatic disease, evidence regarding the efficacy of chemotherapy (CT) combined with bevacizumab or anti-EGFR agents is limited to small studies. This study aimed to assess, in real-world practice, the effectiveness of first-line CT combined with targeted therapies (TT)-either antiangiogenic (AA) or anti-EGFR-compared with CT alone in patients with metastatic SBA (mSBA) and proficient mismatch repair/microsatellite stable (pMMR/MSS) status. PATIENTS AND METHODS:This retrospective multicentre study included all patients receiving at least one cycle of CT with or without TT for mSBA. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. Analyses used inverse probability of treatment weighting (IPTW) in univariable Cox models to account for potential confounding factors that were unbalanced between groups. RESULTS:A total of 255 patients were included: 153 received CT alone, 45 CT+AA, and 16 CT+anti-EGFR as first-line therapy. Median PFS was 8.0 months with CT alone versus 11.9 months with CT+AA (IPTW HR=0.38; 95% CI: 0.29-0.49; p < 0.0001). Median OS was 15.9 versus 23.1 months (IPTW HR=0.38; 95% CI: 0.28-0.51; p < 0.0001). ORR did not differ significantly (33.8% vs 43.2%; p = 0.26). Among 78 patients with RAS wild-type tumours, outcomes did not significantly differ between CT alone and CT+anti-EGFR groups. CONCLUSION:Adding antiangiogenic therapy to CT significantly improved PFS and OS in first-line treatment of mSBA, warranting confirmation through prospective randomized trials.
