To investigate prognostic factors for patients with advanced renal cell carcinoma (RCC) treated with axitinib as second-line therapy.
This study included 35 patients with RCC who received axitinib as ...second-line therapy after the failure of first-line tyrosine kinases inhibitor from November 2012 to March 2017.
In univariate analyses, the following factors were associated with poor prognosis: bone and extrapulmonary metastasis for progression-free survival; and prior nephrectomy, Memorial Sloan Kettering Cancer Center risk classification, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classification of poor, extrapulmonary metastasis and early tumor response for overall survival. Multivariate analyses identified the following factors as independent poor prognostic effects: extrapulmonary metastasis for progression-free survival, and no prior nephrectomy, IMDC risk classification of poor and extrapulmonary metastasis for overall survival.
Axitinib as second-line treatment is effective for patients with pulmonary metastasis alone of RCC, but not for those with extrapulmonary metastasis.
Peptide‑based cancer vaccines have failed to provide sufficient clinical benefits in order to be approved in clinical trials since the 1990s. To understand the mechanisms underlying this failure, the ...present study investigated biomarkers associated with the lower overall survival (OS) among 2,588 patients receiving personalized peptide vaccination (PPV). Survival data were obtained from a database of 2,588 cancer patients including 399 patients with lung, 354 with prostate and 344 with colon cancer. They entered into phase II clinical trials of PPV in which 2 to 4 of 31 warehouse peptides were selected for vaccination on an individual patient basis based on human leukocyte antigen (HLA) class IA‑types and pre‑existing peptide‑specific IgG levels. Higher pre‑vaccination neutrophil, monocyte and platelet counts, and lower pre‑vaccination lymphocyte and red blood cell counts were inversely associated with OS, with higher sensitivities in the proportions of neutrophils and lymphocytes, respectively. The most potent unfavorable and favorable factors for OS were the median percentage of neutrophils (≥64.8%) or percentage of lymphocytes (≥25.1%) with correlation coefficients (R2) of 0.98 and 0.92, respectively. Higher pre‑vaccination levels of c‑reactive protein and other inflammatory soluble factors were inversely associated with OS. Pre‑vaccination peptide‑specific immunity levels had no effect on OS, although lower immune boosting levels were inversely associated with OS. None of the 31 peptides was inversely associated with OS, although a few peptides were positively associated with it. On the whole, the findings of the present study suggested that pre‑vaccination inflammatory signatures, but not those of post‑vaccination immune induction, were associated with lower clinical benefits of PPV.
Nivolumab and ipilimumab (NIVO + IPI) is standard therapy for patients with advanced renal cell carcinoma (RCC). Absolute lymphocyte count (ALC) is a valuable prognostic factor in patients with ...various cancers treated with immune checkpoint inhibitors. Herein, we determined the prognostic value of pretreatment ALC in advanced RCC patients treated with NIVO + IPI as first-line therapy. Data from 46 advanced RCC patients treated with NIVO + IPI between September 2018 and August 2022 were retrospectively reviewed and analyzed. Median progression-free survival (PFS) and overall survival (OS) were significantly shorter in patients with low than high ALC (PFS:
= 0.0095; OS:
= 0.0182). Multivariate analysis suggested that prior nephrectomy hazard ratio (HR) = 3.854, 95% confidence interval (CI) = 1.433-10.359,
= 0.0075 and pretreatment ALC (HR = 2.513, 95% CI = 1.119-5.648,
= 0.0257) were independent factors for PFS. Our new prognostic ALNx model based on ALC and prior nephrectomy suggested that the poor-risk group was a predictor of significantly worse PFS (
< 0.0001) and OS (
= 0.0016). Collectively, the developed ALNx model may be a novel predictor of response in advanced RCC patients treated with NIVO + IPI.
Pembrolizumab, an anti‐programmed death 1 monoclonal antibody, has revolutionized the treatment of metastatic urothelial carcinoma. However, the optimal treatment duration for treatment responders ...has not been established. To address this, we retrospectively assess the treatment outcomes and duration of pembrolizumab for patients whose best response was complete response (CR) or partial response (PR) in a Japanese nationwide cohort of platinum‐refractory metastatic urothelial carcinoma. Of 203 patients whose best response was CR or PR, 83 patients discontinued pembrolizumab before progression. The median pembrolizumab treatment duration was 6.9 months. The 2‐year relapse‐free survival (RFS), treatment‐free survival, and OS rates after discontinuation were 49.0%, 57.4%, and 74.5%, respectively. CR, higher hemoglobin levels, and a better Eastern Cooperative Oncology Group performance status at the time of discontinuation were associated with significantly better RFS. Pembrolizumab was re‐administered to 12 patients. Pembrolizumab re‐challenge resulted in CR, PR, stable disease, and progressive disease in six, three, two, and one patient, respectively. Propensity score‐matched landmark analysis revealed no significant OS difference between patients who continued or discontinued pembrolizumab at 6, 12, and 18 months (p = 0.91, 0.99, and 0.25, respectively). Our findings demonstrated that patients with objective responses had favorable survival outcomes and suggested that pembrolizumab could be discontinued safely in this population. This study should drive further efforts to optimize the treatment duration for pembrolizumab responders.
Favorable relapse‐free survival was observed after pembrolizumab discontinuation in patients with urothelial carcinoma, especially in those with complete responses, higher hemoglobin levels, and better ECOG‐PS at the time of discontinuation. Re‐administration upon progression was effective in 90.9% of the patients, and no difference in overall survival was observed between the patients who continued or discontinued treatment after complete or partial responses.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
To analyze the risks and survival outcomes of non-definitive therapy (nDT) for muscle-invasive bladder cancer (MIBC), which may provide useful information for future treatment selection, the present ...study analyzed 124 patients who were diagnosed with MIBC (cT2-4aN1-2M0) and treated at Kurume University Hospital (Kurume, Japan) with definitive therapy (DT; including radical cystectomy and trimodal therapy) or nDT transurethral resection of bladder tumor (TURBT) monotherapy or TURBT plus chemotherapy. Differences in survival outcomes between the two groups were estimated using the Kaplan-Meier method and analyzed using the log-rank test. Cox proportional hazards regression models were used for multivariate analysis of each survival outcome. Of the 124 patients, 45% were treated with nDT, and among these, 50% were treated with TURBT monotherapy and 50% were treated with TURBT plus chemotherapy. Of the patients who chose definitive treatment, 69% were treated with radical cystectomy. The median age in the nDT group was 77 years, which was significantly higher than that in the DT group. Additionally, the proportion of patients with poor performance status, high Charlson comorbidity index and high neutrophil-lymphocyte ratio values was significantly higher in the nDT group. nDT was associated with significantly reduced overall survival, cancer-specific survival and progression-free survival rates, and was a poor prognostic factor for all survival outcomes compared with DT. In conclusion, nDT was associated with a high cancer-related mortality risk. The most appropriate treatment method should be discussed with the patients after providing them with sufficient information on the risks and benefts of each treatment method.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Synchronous occurrence of triple primary cancers of urinary tract is quite rare and represents a difficult treatment challenge. Here, we report a case of a 78-year-old man with synchronous renal cell ...carcinoma, urothelial carcinoma of urinary bladder and adenocarcinoma of prostate within a short period. To the best of our knowledge, this is the 20th reported of triple primary cancers of urinary tract and the first synchronous case with bone metastasis in the literature.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The HLA‐A11 or ‐A33 allele is found in approximately 18% or 10% of the Asian population, respectively, but each of which is a minor allele worldwide, and therefore no clinical trials were previously ...conducted. To develop a therapeutic peptide vaccine for each of them, we investigated immunological responses of advanced cancer patients with the HLA‐A11+/A11+ (n = 18) or ‐A33+/A33+ (n = 13) allele to personalized peptide vaccine (PPV) regimens. The primary sites of HLA‐A11+/A11+ or ‐A33+/A33+ patients were the colon (n = 4 or 2), stomach (2 or 3), breast (3 or 2), lung and pancreas (2 or 2), and so on. For PPV, a maximum of four peptides were selected from nine different peptides capable of binding to HLA‐A11 and ‐A33 molecules based on the pre‐existing peptide‐specific IgG responses. There were no severe adverse events related to PPV. At the end of the first cycle, peptide‐specific CTL responses were augmented in 4/12 or 2/9 of HLA‐A11+/A11+ or ‐A33+/A33+ patients, while peptide‐specific IgG responses were augmented in 6/14 or 4/10 patients, respectively. Clinical responses consisted of four stable diseases and 14 progressive diseases in HLA‐A11+/A11+patients, versus seven and six in ‐A33+/A33+patients, respectively. Further clinical study of PPV could be recommended because of the safety and positive immunological responses.
IgG boosting were observed in HLA‐A11+/A11+ patients and HLA‐A33+/A33+ patients after personalized peptide vaccine(PPV). The patients with higher rate of changes of peptide‐specific IgG titers after 2nd cycle of vaccination showed longer prognosis than those with lower rate.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Cancer vaccine is one of the attractive treatment modalities for patients with castration-resistant prostate cancer (CRPC). However, because of delayed immune responses, its clinical benefits, ...besides for overall survival (OS), are not well captured by the World Health Organization (WHO) and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Several surrogate markers for evaluation of cancer vaccine, including prostate-specific antigen doubling time (PSADT), are currently sought. The purpose of this study was to assess prospectively the PSA kinetics and immune responses, as well as the efficacy, safety, and biomarkers of personalized peptide vaccination (PPV) in progressive CRPC.
One hundred patients with progressive CRPC were treated with PPV using 2-4 positive peptides from 31 candidate peptides determined by both human leukocyte antigen (HLA) class IA types and the levels of immunoglobulin G (IgG) against each peptide. The association between immune responses and PSADT as well as overall survival (OS) was studied.
PPV was safe and well tolerated in all patients with a median survival time of 18.8 months. Peptide-specific IgG and T-cell responses strongly correlated with PSADT (p < 0.0001 and p = 0.0007, respectively), which in turn showed correlation with OS (p = 0.018). Positive IgG responses and prolongation of PSADT during PPV were also significantly associated with OS (p = 0.001 and p = 0.004) by multivariate analysis.
PSADT could be an appropriate surrogate marker for evaluation of the clinical benefit of cancer vaccine. Further randomized trials are needed to confirm these results.
UMIN000001850.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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