Among men with high-risk, nonmetastatic, castration-resistant prostate cancer, the addition of enzalutamide to androgen-deprivation therapy improved overall survival by nearly a year as compared with ...ADT alone: median survival was 67 months with enzalutamide plus ADT and 56 months with ADT alone.
Lenvatinib plus either pembrolizumab or everolimus was compared with sunitinib as first-line therapy for advanced renal cell cancer. Progression-free survival was significantly longer with lenvatinib ...plus pembrolizumab than with sunitinib. Lenvatinib plus everolimus was also more effective than sunitinib, but the difference was smaller.
A number of agents are now approved for the treatment of renal cancer. A comparison of two agents, pazopanib and sunitinib, showed similar levels of antitumor activity but distinct side-effect ...profiles. Symptoms affecting quality of life were somewhat worse with sunitinib.
Renal-cell carcinoma is the most common kidney cancer.
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Up to 30% of patients have metastases at the time of the initial diagnosis.
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Systemic treatment for patients who have metastatic renal-cell carcinoma with a clear-cell histologic component has shifted from cytokines to drugs targeting angiogenesis. Sunitinib, pazopanib, and five other agents have been approved by the Food and Drug Administration for the treatment of clear-cell, metastatic renal-cell carcinoma.
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Among the tyrosine kinase inhibitors, pazopanib and sunitinib are first-line treatment options.
Sunitinib has been compared with interferon alfa in patients who had not previously received systemic therapy for renal-cell carcinoma,
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whereas . . .
Outcomes of castration-sensitive prostate cancer (CSPC) have improved owing to new therapies and early treatment, previously reserved for castration-resistant disease (CRPC). Prostatic-specific ...antigen (PSA) remains the most used marker to follow-up patients under treatment, but only limited data are available about the prognostic role of its changes over time and the impact of response to subsequent therapies. This analysis aims to assess the prognostic role of the magnitude and velocity of PSA response in CSPC and describe how this may affect the outcome to subsequent treatment outcomes in CRPC.
A retrospective analysis was performed on patients with de novo CSPC referring to six oncology centers in Italy. Clinical and pathological features were recorded. PSA response (PSA50), defined as a decrease > 50% compared to baseline, PSA velocity (PSAv), defined as any decrease in PSA levels over time and the deep and fast PSA response (4mPSA50), defined as the PSA response reached within the threshold of 4 months from the beginning of androgen deprivation therapy (ADT) have been evaluated for their impact on survival. Survivals were estimated using the Kaplan-Meier method and compared across groups using the log-rank test. Cox proportional-hazard models, stratified according to baseline characteristics, were used to estimate hazard ratios for overall survival (OS).
A totals of 94.4% of patients had PSA50, which was correlated to longer OS compared to patients without PSA50 (56.0 vs. 14.8 months; p<0.001). The median PSAv was 6.9 (ng/dl)/month, which was predictive for longer OS: Each decrease of 1 (ng/dl)/month was able to improve OS by 0.2% (HR=0.998, 95%CI=0.997-1.000; p=0.008). A total of 47.9% of patients reached 4mPSA50, with a median OS and progression-free survival (PFS) to ADT-based therapy of 101.0 and 23.4 months compared to 41.9 and 11.0 months for those who did not (p<0.001), respectively. The independent prognostic role of 4mPSA50 was retained even when evaluated in multivariable analysis adjusted for other baseline characteristics and early docetaxel for CSPC. In CRPC, 4mPSA50 evaluated during CSPC retains its prognostic role even if it does not predict a different outcome between patients treated with abiraterone/enzalutamide or taxanes.
Achieving a deep and fast PSA response correlates with a better outcome in patients with de novo mCSPC, also positively influencing the prognosis of the subsequent first-line therapy for CRPC disease.
Inhibitors of fibroblast growth factor receptor (FGFR) represent an outstanding treatment approach for selected patients with urothelial cancer (UC). These agents are changing the clinical approach ...to a subgroup of UC, the luminal-papillary subtype, characterized by FGFR mutations, fusions, or amplification. In this review, we provide an overview of the results of recent clinical trials on FGFR tyrosine kinase inhibitors (TKIs) currently in clinical development for the treatment of UC: erdafitinib, rogaratinib, infigratinib, and the monoclonal antibody vofatamab. The Food and Drug Administration recently granted accelerated approval to erdafitinib for patients with advanced UC with alterations of FGFR2 or FGFR3 after progression on platinum-based chemotherapy. We also look at future therapeutic options of combination regimens with immune-checkpoint inhibitors as strategies for improving the antitumor effects of this class of drug, and for preventing or delaying the development of resistance.
Statins are widely used in an ageing population, including subjects with solid malignancies. However, no conclusive evidence is currently available on their potential influence on patients' outcome. ...We aimed to assess whether statin exposure affects the survival of patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab.
Medical records of patients with documented mRCC treated with second- or third-line nivolumab were reviewed at ten institutions from Italy, Spain and the USA. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall clinical benefit. Univariate and multivariate analyses were used to explore the association of variables of interest with survival.
A total of 219 patients with mRCC receiving nivolumab between January 2016 and September 2021 were eligible for inclusion in this study; 59 (27%) were statin users. The median OS (34.4 versus 18.6 months, p = 0.017) and PFS (11.7 versus 4.6 months, p = 0.013) resulted apparently longer in statin users. Stratified by age, longer median OS and PFS were associated with statin exposure in both patients aged ≥70 y (median OS: 21.4 versus 10.1 months, p = 0.047; median PFS: 16.4 versus 4.6 months, p = 0.022) and <70 y (median OS: 34.4 versus 21.4 months, p = 0.043; median PFS: 10.3 versus 4.6 months, p = 0.042). Overall clinical benefit resulted higher in statin users than non-users (71% versus 54%, p = 0.030).
Our study suggests a prognostic impact of statin use in patients receiving nivolumab for mRCC.
•Statins are widely used in patients with solid malignancies.•We assessed the impact of statin exposure in patients with metastatic renal cell carcinoma treated by nivolumab.•Statin users showed longer median overall survival and progression-free survival.•Statin exposure was correlated with increased overall clinical benefit.•The synergy between statins and nivolumab should be carefully elucidated.
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•Treatment options for prostate cancer (PC) have greatly expanded in the last years.•Despite improvements in diagnosis and treatment options, PC remains one of the most frequent ...causes of mortality in men.•The cyclin-dependent kinases (CDK) pathway has a fundamental role for carcinogenesis.•CDK-inhibitors are novel agents representing a promising treatment approach in PC.•Several trials are evaluating the role of these agents in different stages of PC.
The rapidly expanding scenario of treatment options for patients affected by prostate cancer (PC) is leading to improved outcomes; however, PC still represents one of the most frequent causes of male mortality. Thus, while translational research is trying to unravel the molecular landscape underlying carcinogenesis, disease progression and treatment resistance, several clinical trials are evaluating novel options to further expand therapeutic options.
The cyclin-dependent kinases (CDK)-pathway represents a promising therapeutic target for different cancer types; due to the pivotal role of this pathway in the regulation of PC cell cycle, three CDK4/6-inhibitors (abemaciclib, palbociclib and ribociclib) are currently being investigated in several clinical trials.
In this paper, we review the current knowledge on CDK-pathway and the mechanism of action of CDK-inhibitors; we discuss the biological rationale for their use in PC and the state of the art of clinical trials focused on the demonstration of their potential role in early or advanced stage, in hormone-sensitive and castration-resistant state. Finally, the potential application of precision oncology for treatment selection in PC is discussed.
Residual lesions after chemotherapy are frequent in metastatic seminoma. Watchful waiting is recommended for lesions < 3 cm as well as for fluorodeoxyglucose (FDG) positron emission tomography ...(PET)-negative lesions ≥ 3 cm. Information on the optimal management of PET-positive residual lesions ≥ 3 cm is lacking.
We retrospectively identified 90 patients with metastatic seminoma with PET-positive residual lesions after chemotherapy. Patients with elevated α-fetoprotein or nonseminomatous histology were excluded. We analyzed the post-PET management and its impact on relapse and survival and calculated the positive predictive value (PPV) for PET.
Median follow-up time was 29 months (interquartile range IQR, 10 to 62 months). Median diameter of the largest residual mass was 4.9 cm (range, 1.1 to 14 cm), with masses located in the retroperitoneum (77%), pelvis (16%), mediastinum (17%), and/or lung (3%). Median time from the last day of chemotherapy to PET was 6.9 weeks (IQR, 4.4 to 9.9 weeks). Post-PET management included repeated imaging in 51 patients (57%), resection in 26 patients (29%), biopsy in nine patients (10%) and radiotherapy in four patients (4%). Histology of the resected specimen was necrosis in 21 patients (81%) and vital seminoma in five patients (19%). No biopsy revealed vital seminoma. Relapse or progression occurred in 15 patients (17%) after a median of 3.7 months (IQR, 2.5 to 4.9 months) and was found in 11 (22%) of 51 patients on repeated imaging, in two (8%) of 26 patients after resection, and in two (22%) of nine patients after biopsy. All but one patient who experienced relapse were successfully treated with salvage therapy. The PPV for FDG-PET was 23%.
FDG-PET has a low PPV for vital tumor in residual lesions after chemotherapy in patients with metastatic seminoma. This cautions against clinical decisions based on PET positivity alone.
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