INTRODUCTION: The dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) highlights the urgent need for novel therapeutic strategies. Immune checkpoint inhibitors (ICIs) seem to be ineffective in most PDAC studies. Therefore, we conducted an open-label, multicenter phase 1/2 study (CA209-9KH) to evaluate the safety of stereotactic radiotherapy (SRT) and sequential ICI therapy in PDAC, as well as to validate the efficacy of this regimen as a potential activator of antitumor immunity. METHODS: Patients aged ≥ 18 years with unresectable non-metastatic PDAC following four FOLFIRINOX induction cycles were included. Treatment comprised SRT (4 × 8 Gy) and sequential nivolumab administration until disease progression or unacceptable toxicity. The primary endpoints were safety and toxicity assessment. Secondary endpoints included progression-free survival (PFS), overall survival (OS), biomarker evaluation, and quality of life (QoL) analysis. RESULTS: Twenty-two patients were screened, with 15 enrolled. Eleven (median) nivolumab cycles were administered. SRT demonstrated low and clinically nonsignificant toxicity, whereas nivolumab toxicity aligned with prior safety profiles, without grade 4-5 events observed. Three patients discontinued therapy owing to toxicity. Median PFS and OS were 8.1 and 13.0 months, respectively, with 12-month PFS and OS rates of 0% and 66.7%, respectively, and a 24-month OS rate of 8.9%. Biomarker levels correlated with clinical or radiological disease control. Patient-reported QoL remained acceptable, deteriorating with disease progression. CONCLUSION: SRT and nivolumab therapy exhibited manageable toxicity profiles consistent with previous findings; however, long-term treatment responses were not achieved with this regimen in locally advanced PDAC. Another strategy to trigger antitumor immunity in PDAC needs to be sought. TRIAL REGISTRATION: EudraCT: 2017-003404-52; ClinicalTrials.gov: NCT04098432.
- Publikační typ
- časopisecké články MeSH
Imunoterapie se stala běžně používanou systémovou léčbou pokročilého a metastatického karcinomu z renálních buněk. Role radioterapie u karcinomu ledvin se přesunula z paliativní indikace ke stereotaktické, kraniální a extrakraniální, radioterapii a radiochirurgii, která může být účinnou alternativou k chirurgickému řešení, zejména u oligometastatických onemocnění. Slibně se jeví hypotéza, že radioterapie může aktivovat imunitní systém a tím zvýšit účinnost imunologické léčby. Bohužel je stále velmi málo klinických dat o skutečné účinnosti kombinace radioterapie a imunoterapie pro karcinom ledvinových buněk. Skutečný klinický přínos mohou potvrdit až výsledky randomizovaných klinických studií.
Immunotherapy has become a commonly used systemic treatment for advanced and metastatic renal cell carcinoma. The role of radiotherapy in renal cancer has shifted from palliative irradiation to the stereotactic, cranial and extracranial, radiotherapy and radiosurgery, which can be an effective alternative to surgery, especially in oligometastatic disease. The hypothesis that radiotherapy can activate the immune system and thus increase the effectiveness of immunological treatment seems promising. Unfortunately, there is still very little clinical data on the true efficacy of the combination of radiotherapy and immunotherapy for renal cell carcinoma. The true clinical benefit can only be confirmed by the results of randomized clinical trials.
- MeSH
- inhibitory kontrolních bodů terapeutické užití MeSH
- ipilimumab terapeutické užití MeSH
- karcinom z renálních buněk * imunologie radioterapie terapie MeSH
- kombinovaná terapie MeSH
- lidé MeSH
- metastázy nádorů radioterapie terapie MeSH
- nivolumab terapeutické užití MeSH
- radiochirurgie * metody MeSH
- stereotaktické techniky MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
The following main treatment approaches are currently used in locally advanced adenocarcinomas of the oesophagus and gastrooesophageal junction (GOJ): preoperative chemoradiotherapy and surgery, and perioperative chemotherapy and surgery. While preoperative chemoradiotherapy is used primarily in oesophageal tumours, perioperative chemotherapy is the treatment of choice in Western countries for gastric cancer. The optimal treatment strategy for GOJ adenocarcinoma is still not clear. In comparison to other malignancies, biomarkers are used as predictive factors in distal oesophageal and GOJ adenocarcinomas in a very limited way, and moreover, only in metastatic stages (e.g., HER2 status, or microsatellite instability status). The aim of the article is to provide an overview of current treatment options in locally advanced adenocarcinomas of oesophagus and GOJ based on the latest evidence, including the possible potential of predictive biomarkers in optimizing treatment.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
