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Background: Renal cell carcinoma with sarcomatoid differentiation is a highly aggressive form of kidney cancer. Objective: We aimed to analyze the outcomes of patients treated with cabozantinib for metastatic renal cell carcinoma with sarcomatoid features. Methods: We retrospectively collected data from 16 worldwide centers. Overall survival and progression-free survival were analyzed using Kaplan–Meier curves. Cox proportional models were used for univariate and multivariate analyses. Results: We collected data from 66 patients with metastatic sarcomatoid renal cell carcinoma receiving cabozantinib as second-line (51%) or third-line (49%) therapy. The median progression-free survival from the start of cabozantinib was 7.59 months (95% confidence interval [CI] 5.75−17.49) and was longer in male patients (8.81 vs 5.95 months, p = 0.042) and in patients without bone metastases (7.59 vs 5.11 months, p = 0.010); the median overall survival was 9.11 months (95% CI 7.13−23.80). At the multivariate analysis, female sex (hazard ratio = 1.81; 95% CI 1.02−3.37,p = 0.046), bone metastases (hazard ratio = 2.62; 95% CI 1.34−5.10, p = 0.005), and International Metastatic Renal Cell Carcinoma Database Consortium criteria (hazard ratio = 3.04; 95% CI 1.54−5.99, p = 0.001) were significant predictors of worse overall survival. Conclusions: Our data show that cabozantinib is active in pretreated patients with sarcomatoid renal cell carcinoma. Biomarkers are needed in this field to select patients for multi-kinase inhibitors or other options.

Objective: To investigate the role of CTLA-4, PD-1 (programmed death-1), and PD-L1 (programmed death-ligand 1) single nucleotide polymorphisms (SNPs) in predicting clinical outcome of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). Methods: A total of 166 consecutive patients were included. We correlated SNPs with clinical benefit, progression-free survival, time to treatment failure, and overall survival and evaluated the incidence of SNPs in nonresponder and long clinical benefit groups. Results: Considering the entire cohort, no correlation was found between SNPs and clinical outcome; however, PD-L1 rs4143815 SNP and the long clinical benefit group showed a statistically significant association ( p = 0.02). The nonresponder cohort displayed distinctive PD-L1 haplotype ( p = 0.05). Conclusion: PD-L1 SNPs seem to be marginally involved in predicting clinical outcome of NSCLC treated with ICI, but further investigations are required.

In the last 10 years, many new therapeutic options have been approved in advanced prostate cancer (PCa) patients, granting a more prolonged survival in patients with metastatic disease, which, nevertheless, remains incurable. The emphasis on immune checkpoint inhibitors (ICIs) has led to many trials in this setting, with disappointing results until now. Therefore, we discuss the immunobiology of PCa, presenting ongoing trials and the available clinical data, to understand if immunotherapy could represent a valid option in this disease, and which subset of patients may be more likely to benefit. Current evidence suggests that the tumor microenvironment needs a qualitative rather than quantitative evaluation, along with the genomic determinants of prostate tumor cells. The prognostic or predictive value of immunotherapy biomarkers, such as PD-L1, TMB, or dMMR/MSI-high, needs further evaluation in PCa. Monotherapy with immune checkpoint inhibitors (ICIs) has been modestly effective. In contrast, combined strategies with other standard treatments (hormonal agents, chemotherapy, PARP inhibitors, radium-223, and TKIs) have shown some results. Immunotherapy should be better investigated in biomarker-selected patients, particularly with specific pathway aberrations (e.g., AR-V7 variant, HRD, CDK12 inactivated tumors, MSI-high tumors). Lastly, we present new possible targets in PCa that could potentially modulate the tumor microenvironment and improve antitumor activity with ICIs.

// Daniele Santini 1 , Raffaele Ratta 2 , Francesco Pantano 1 , Delia De Lisi 1 , Marco Maruzzo 3 , Luca Galli 4,6 , Elisa Biasco 4 , Azzurra Farnesi 4 , Sebastiano Buti 5 , Cora Nanette Sternberg 6 , Linda Cerbone 6 , Giuseppe Di Lorenzo 7 , Silvia Spoto 8 , Michelle Sterpi 1 , Ugo De Giorgi 9 , Rossana Berardi 10 , Mariangela Torniai 10 , Andrea Camerini 11 , Francesco Massari 12 , Giuseppe Procopio 2 and Giuseppe Tonini 1 1 Campus Bio-Medico University of Rome, Department of Medical Oncology, Rome, Italy 2 Fondazione IRCCS, Istituto Nazionale dei Tumori, Oncology Unit 1, Milan, Italy 3 Istituto Oncologico Veneto, IOV-IRCCS, Medical Oncology 1 Unit, Padova, Italy 4 University Hospital of Pisa, Oncology Unit 2, Pisa, Italy 5 University Hospital of Parma, Medical Oncology, Parma, Italy 6 San Camillo and Forlanini Hospitals, Department of Medical Oncology, Rome, Italy 7 Department of Clinical Medicine & Surgery, Oncology Division, University Federico II, Naples, Italy 8 Campus Bio-Medico University of Rome, Department of Internal Medicine, Rome, Italy 9 IRCCS Istituto Scientifico Romagnolo per lo studio e la Cura dei Tumori, Department of Medical Oncology, Meldola, Italy 10 Universita Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Medical Oncology Unit, Ancona, Italy 11 Versilia Hospital and Istituto Toscano Tumori, Medical Oncology, Lido di Camaiore, Italy 12 S.Orsola-Malpighi Hospital, Division of Oncology, Bologna, Italy Correspondence to: Delia De Lisi, email: // Keywords : metastatic renal cell carcinoma (mRCC), oligoprogression, pazopanib, sunitinib, targeted therapy Received : April 25, 2016 Accepted : June 19, 2017 Published : August 07, 2017 Abstract Locoregional treatment with radical intent should be considered during therapy with targeted agents in patients with metastatic renal cell carcinoma (mRCC) in order to achieve a complete response, especially in the setting of an oligo-progression in one or more metastatic sites. We retrospectively enrolled 55 patients who experienced a disease oligo-progression after at least 6 months from the beginning of first-line therapy in one or more metastatic sites radically treated with locoregional treatments. Post-first-oligo-progression overall survival (PFOPOS) and post-first-oligo-progression free survival (PFOPFS) were evaluated. The global median PFOPOS and PFOPFS were 37 months and 14 months respectively. Patients who continued the same therapy after a locoregional treatment on a site of progression had a significantly longer mPFOPOS compared to patients who changed therapy (39 vs 11 months, p =0.014). An advantage in mPFOPOS was also observed in patients with a Memorial Sloan-Kettering Cancer Center (MSKCC) good risk score compared to patients of the intermediate risk group (39 vs 29 months, p =0.036); patients with bone metastases had a longer mPFOPOS compared to those with visceral metastases (not reached vs 31 months, p =0.045). The only independent predictor of poor prognosis, in terms of PFOPOS at multivariate analysis ( p =0.007), proved out to be change of treatment after first progression. In this paper we aim to illustrate that continuing the same systemic therapy, after a radical locoregional treatment on a site of progression, seems to be associated with a prolongation of mPFOPOS.