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
BACKGROUND: A 27-year-old man was referred to an oncology department following right orchiectomy for a stage I testicular seminoma at high risk for recurrence. He presented 6 weeks after the orchiectomy with an atrophic left testis, fatigue and a history of infertility. INVESTIGATIONS: Measurement of serum levels of urea, electrolytes, liver enzymes, bilirubin, human chorionic gonadotropin, alpha-fetoprotein, lactate dehydrogenase, testosterone and luteinizing hormone, full blood count, and left testicular biopsy. DIAGNOSIS: Tubular atrophy of the left testis with islands of intratubular germ cell neoplasia (ITGCN), and hypergonadotropic hypogonadism. MANAGEMENT: The patient received adjuvant chemotherapy as a single dose of carboplatin for the seminoma at high risk for recurrence, and testosterone replacement for the hypergonadotropic hypogonadism. Radiotherapy to the ITGCN-bearing solitary testis or a second orchiectomy was offered to prevent the progression of ITGCN into an invasive germ cell tumor. After exploring his options with regards to fertility treatment, the patient chose to undergo second orchiectomy with a subsequent, unsuccessful, attempt at sperm retrieval. At 20 months after diagnosis of his initial seminoma the patient showed no sign of recurrence.
- MeSH
- androgeny terapeutické užití MeSH
- antitumorózní látky terapeutické užití MeSH
- atrofie MeSH
- dospělí MeSH
- germinální a embryonální nádory patologie MeSH
- hypogonadismus diagnóza terapie MeSH
- karboplatina terapeutické užití MeSH
- lidé MeSH
- mnohočetné primární nádory patologie terapie MeSH
- orchiektomie MeSH
- semenotvorné kanálky patologie MeSH
- seminom chirurgie patologie MeSH
- testikulární nádory chirurgie patologie MeSH
- testis patologie chirurgie MeSH
- testosteron terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
