The JCOG1806 trial (jRCTs031190129) is underway to evaluate the omission of surgery in patients with human epidermal growth factor receptor (HER2)-positive early breast cancer who have a clinical complete response (cCR) after primary systemic therapy (PST). We aimed to assess the cCR rate in this trial and identify predictive factors. HER2-positivity was defined as an immunohistochemistry (IHC) score of 3 + or in situ hybridization-positivity. A cCR was defined as the absence of detectable lesions upon palpation, contrast-enhanced magnetic resonance imaging, and ultrasonography; biopsy-based confirmation was optional in hormone receptor (HR)-negative cases and mandatory in HR-positive cases. Multivariate logistic regression analyses were used to identify predictors of a cCR. The cCR rate was 57.6
Oligometastasis is a concept that refers to the condition between localized cancer and widespread distant metastases; however, a consensus on the definition has yet to be reached. Metastasis-directed therapy (MDT) has recently been established to incorporate local therapy, such as radiotherapy and surgery, for distant metastases. Previous trials have proposed the possibility of long-term survival with the administration of MDT for patients with oligometastases. However, the efficacy and safety of MDT have not been sufficiently validated. We are conducting this clinical trial to confirm the superiority of MDT combined with subtype-specific systemic drug therapy over systemic drug therapy alone in patients with oligometastatic breast cancer. Here, "oligometastases" are defined as tumors with a maximum diameter ≤ 3 cm and total number ≤ 3. The primary endpoint is overall survival. We intend to enroll 340 patients from 62 institutions over a 3-year period. This trial has been registered in the Japan Registry of Clinical Trials (jRCTs031230439).
Specific human leukocyte antigen (HLA) genotypes, particularly HLA-DQA1*05, have been proposed as predictors for infliximab (IFX) treatment response and immunogenicity in Western populations. However, the evidence regarding the effect of HLA-DQA1*05 remains limited in East Asian populations, including in Japan. Moreover, HLA-DQA1*05 frequency differs substantially from those in Western populations. Comprehensive analyses of the association between HLA alleles and IFX treatment outcomes may contribute to the identification of novel prognostic markers for IFX therapies. We retrospectively analyzed 301 biologic-naïve Japanese patients with inflammatory bowel disease (IBD). IFX persistence was assessed at both 2-digit and 4-digit HLA allele resolutions, and associations with anti-drug antibody levels at 1 year after the initiation of IFX therapy were evaluated. At the 2-digit resolution analysis, HLA-DQB1*03 (hazard ratio [HR] = 2.39, p = 1.89E-06) and HLA-DQA1*05 (HR = 1.99, p = 3.91E-04) were significantly associated with early IFX discontinuation. At the 4-digit resolution analysis, HLA-DQB1*03:01 (HR = 2.03, p = 9.42E-05) and HLA-DQA1*05:05 (HR = 2.18, p = 4.42E-05) showed similar associations. All HLA-DQA1*05:05 alleles formed haplotypes with HLA-DQB1*03:01. Importantly, HLA-DQB1*03:01 was also associated with early discontinuation of IFX even when it formed haplotypes with alleles other than HLA-DQA1*05:05. Both HLA-DQB1*03:01 and HLA-DQA1*05:05 were significantly associated with elevated anti-drug antibody levels (p = 3.23E-03 and 3.54E-03, respectively). HLA-DQB1*03:01 encompasses the information of HLA-DQA1*05:05 and serves as a strong genetic predictor of IFX treatment persistence and immunogenicity in Japanese patients with IBD, offering a potential biomarker for personalized therapy.
BACKGROUND:This randomized controlled trial provided LC16m8 pre-exposure prophylaxis to high-risk individuals to assess its efficacy for mpox prevention, safety, and immunogenicity. METHODS:This multicenter, randomized, open-label trial enrolled men and women aged ≥18 years at high risk of mpox. Participants were randomly assigned 1:1 to early- or late-vaccination groups. The primary endpoint was vaccine efficacy (VE) against mpox. Secondary endpoints included VE against severe mpox, symptoms, "take" incidence, adverse events (AEs), and immunogenicity in participants with human immunodeficiency virus (HIV). RESULTS:In total, 570 and 565 participants were assigned to early- and late-vaccination groups, respectively, with 530 and 476 vaccinated. The median age was 41 years; 99.7% were male, 89.7% were Japanese, and 34.4% had HIV. No mpox cases occurred, precluding VE calculations. The take rates were 89.5% (with HIV) and 93.9% (without HIV). AEs occurred in 97.2% and 98.2% of participants with and without HIV, respectively. No fatal AEs were observed. Serious adverse events (SAEs) were observed in 2/352 (0.6%) and 3/654 (0.5%) of participants with and without HIV, respectively, of which 1 SAE causally related to vaccination occurred in a participant without HIV. Seroconversion rates for LC16m8 and MPXV were 96.2% and 69.2%, respectively, in participants with HIV, and 92.0% and 52.0%, respectively, in individuals without HIV. CONCLUSIONS:LC16m8 efficacy in mpox remains inconclusive. However, in individuals with well-controlled HIV, it was immunogenic and raised no significant safety concerns, suggesting its suitability for targeted vaccination of at-risk groups. (Japan Registry of Clinical Trials number, jRCT1031230137).
Objective:Progressive pulmonary fibrosis (PPF) is a chronic interstitial lung disease (ILD) characterised by fibrotic progression and poor prognosis, with effective treatment strategies for previously untreated patients remaining unclear. This study evaluated the efficacy and safety of upfront combination therapy with anti-inflammatory and antifibrotic agents in previously untreated PPF patients. Methods:This multicentre, single-arm phase 2 study enrolled 34 patients with ILD (including unclassifiable idiopathic interstitial pneumonia, idiopathic nonspecific interstitial pneumonia, fibrotic hypersensitivity pneumonitis and rheumatoid arthritis-associated ILD) all with evidence of PPF. Tacrolimus (0.0375 mg·kg-1 twice daily) and prednisolone (10 mg once daily) were initiated on day 1, with nintedanib (150 mg twice daily) added on day 8. The tacrolimus dosage was adjusted to maintain blood trough levels. The primary end-point was the change in the relative decline slope for forced vital capacity % predicted (%FVC) between before and after treatment. Results:The protocol treatment was associated with a substantial improvement in the relative %FVC decline slope, from -20.9% per year before to +11.2% per year after treatment. Subgroup analysis revealed greater improvement in patients with an increased lymphocyte percentage in bronchoalveolar lavage fluid or elevated blood biomarkers. Adverse events, such as diarrhoea (67.6%) and hepatic dysfunction (29.4%), were manageable, with no severe cases or treatment discontinuations. Conclusion:Early combination therapy with tacrolimus, prednisolone and nintedanib was associated with improved pulmonary function and was well tolerated in previously untreated PPF patients. Our findings suggest the potential of this regimen as an initial treatment strategy, but further validation in larger randomised controlled trials is warranted.
