Background: Trastuzumab and chemotherapy is the standard first-line treatment in human epidermal growth factor receptor 2 (HER2)-positive advanced gastro-oesophageal cancer. The objective was to develop a predictive model for overall survival (OS) and progression-free survival (PFS) in patients treated with trastuzumab. Methods: Patients with HER2-positive advanced gastro-oesophageal adenocarcinoma (AGA) from the Spanish Society of Medical Oncology (SEOM)-AGAMENON registry and treated first line with trastuzumab and chemotherapy between 2008 and 2021 were included. The model was externally validated in an independent series (The Christie NHS Foundation Trust, Manchester, UK). Results: In all, 737 patients were recruited (AGAMENON-SEOM, n = 654; Manchester, n = 83). Median PFS and OS in the training cohort were 7.76 [95% confidence interval (CI), 7.13–8.25] and 14.0 months (95% CI, 13.0–14.9), respectively. Six covariates were significantly associated with OS: neutrophil-to-lymphocyte ratio, Eastern Cooperative Oncology Group performance status, Lauren subtype, HER2 expression, histological grade and tumour burden. The AGAMENON-HER2 model demonstrated adequate calibration and fair discriminatory ability with a c-index for corrected PFS/OS of 0.606 (95% CI, 0.578–0.636) and 0.623 (95% CI, 0.594–0.655), respectively. In the validation cohort, the model is well calibrated, with a c-index of 0.650 and 0.683 for PFS and OS, respectively. Conclusion: The AGAMENON-HER2 prognostic tool stratifies HER2-positive AGA patients receiving trastuzumab and chemotherapy according to their estimated survival endpoints.
Aim Assess the effectiveness and safety of nivolumab versus cetuximab in
patients with R/M HNSCC, as well as to analyze possible prognostic
factors for response to treatment with nivolumab. Methods We conducted
an observational, retrospective, descriptive study of patients with R/M
HNSCC who initiated treatment with nivolumab or cetuximab monotherapy in
two periods of equivalent duration. Overall efficacy was measured in
progression-free survival (PFS) and overall survival (OS); safety was
evaluated using the CTCAE (Common Terminology Criteria for Adverse
Events) classification version 5.0 of the National Cancer Institute
(NCI). Results Median overall survival (OS) was 9.1 months with
nivolumab (n=34) vs. 6.3 months with cetuximab (n=12)(HR=0.5; 95%CI:
0.24-1.03; p=0.058). Progression free survival (PFS) were 4.3 for
nivolumab and 4.65 months for cetuximab (HR=0.59; 95%CI: 0.29-1.19;
p=0.14). Any grade adverse events (AEs) were reported in 97% and 100%
of the patients treated with nivolumab and cetuximab. Serious AEs were
observed in 26% and 58% of the patients respectively. Elevated albumin
values, lymphocytosis, neutropenia and elevated neutrophil/lymphocyte
ratio values have positive prognostic value on the response to nivolumab
in R/M CCECC. Conclusion Effectiveness of nivolumab in terms of OS
remains superior to cetuximab. OS, PFS and severe or any grade AEs were
superior in both arms of our study than in the clinical trials. The AEs
profile of nivolumab differs in our study from the clinical trials’
observations. We have identified four positive statistically significant
prognostic variables on the response to nivolumab in R/M HNSCC.
strategies deeply changed when Ivacaftor (2015) and the combination therapy Ivacaftor/Tezacaftor/Elexacaftor (ETI) (2021) were marketed. At this moment ETI therapy is licensed to treat CF's patients>6 years with at least one F508del mutation, the most common one; however, patients with rarer CFTR's mutations don't have access to this therapy. Aim and Objectives With this work we would like to report the use of the combination therapy Ivacaftor-ETI in two young patients with rare CFTR's mutations: the N1303K/ 2183AA>G and the W1282X/N1303K. Material and Methods Starting from the off-label authorisations from January-2015 to June-2022 by our Hospital Committee (composed with a Clinician, a Pharmacologist and a Hospital Pharmacyst) in accord to Law 94/98, we identified patients that required off-label CFTR modulators' combination therapy due to their CFTR's rare mutations and in vitro response to ETI therapy. For these we analysed: age at the beginning of the therapy, gender, type of mutation, clinical manifestations, period of therapy, Adverse Drug Reactions (ADRs) notified. Results Only in 2022 two patients were authorised to use offlabel CFTR modulators' combination therapy due to their rare CFTR's mutations. The first patient (P1) was a female, 20 years, W1282X/N1303K mutations; her clinical history showed meconium ileus, serious pneumopaty and she often required antibiotic therapy due to her lungs infections. The second patient (P2) was a female, 19 years, N1303K/ 2183AA>G mutations; her clinical history showed pancreatic and lungs insufficiency, BMI<14, infections induced by multidrug resistant Pseudomonas and Mycobacterium Abscessus, D hypovitaminosis. At first, Hospital Committee authorised 3 cycles of therapy for P1 and 4 cycles (28 days for each cycle) for P2; both of them were authorised to prolonge their therapy due to clinical evident efficacy. No significant ADRs related to treatment were notified. Conclusion and Relevance CFTR modulators are small molecules that directly impact and achieve the function of CFTR channel. They give long-term improvements in clinical outcomes and we hope more research on their efficacy in patients with rarer CFTR's mutations.
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