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For rare cancers, challenges in establishing standard therapies are greater than those for major cancers, and effective methods are needed. MASTER KEY Project is a multicenter study based in Japan, with two main parts: prospective registry study and multiple clinical trials. Advanced rare cancers, cancers of unknown primary origin, and those with rare tissue subtypes of common cancers are targeted. The registry study accumulates highly reliable consecutive data that can be used for future drug development. The multiple trials are conducted simultaneously, targeting either a specific biomarker or a rare tumor type of interest. The first interim data set from the registry part presented here shows the prevalence of genetic abnormalities, response rates, survival rates, and clinical trial enrollment rates. From May 2017 to April 2019, 560 patients (mean age = 53) were enrolled in the project. Frequent cancer types included soft tissue sarcomas, neuroendocrine tumors, and central nervous system tumors. Among the 528 patients with assessable data, 69% (364/528) had next-generation sequencing tests, with 48% (176/364) harboring an "actionable" alteration. Seventy-one (13%) patients have been enrolled in one of the clinical trials, with an accrual rate of 3.94 patients/month. A descriptive analysis of biomarker-directed or non-biomarker-directed treatment survival was performed. This project is expected to accelerate development of treatments for rare cancers and show that comprehensive platform trials are an advantageous strategy., (© 2020 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Tumor profiling has been shown to benefit patients with rare or refractory metastatic cancer, but several limitations hamper its use in daily clinical practice. We aim to assess the added benefit of a comprehensive tumor profiling, including factors predictive of response to targeted and cytotoxic therapy, in the treatment of refractory or rare solid tumors outside of a formal clinical trial. Patients were included between 2013 and 2017. Multiplatform comprehensive tumor profiling (CTP) was performed on FFPE specimens. Tumor response was evaluated by imaging using the RECIST criteria version 1.1. The PFS ratio was defined as PFS under CTP-guided therapy (PFS2)/PFS under previous standard therapy (PFS1). A clinical benefit was identified if the PFS ratio exceeded the 1.3 threshold value. In total, 184 patients were enrolled among whom 104 were evaluable for the PFS ratio. Objective response rates (ORR) were equal to 25% (CI95: 16.6-33.4%) and 36.5% (CI95: 27.2-45.8%) on the last therapy before CTP and on the CTP-guided therapy respectively (P-value=0.058 on paired proportion comparison test). The proportion of patients achieving a PFS2/PFS1 ratio≥1.3 was equal to 50%. The median PFS1 was statistically lower than PFS2 (120 days compared to 184 days respectively, P-value log rank 0.01). These results confirm the feasibility and the added benefit of a CTP in patients with refractory tumors in daily clinical practice especially in patients not able to enter a clinical trial., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Adult prostatic sarcoma (PS) is a rare disease. While surgery is considered the standard approach, the role of other therapies is not completely established. We report results of the largest multicentric contemporary cohort of PS patients., Materials and Methods: This study included 61 adult PS patients treated in 16 American and European Institutions. Median age was 64.4 years (range: 22-87). Curative surgery was delivered in 48 patients (prostatectomy = 26, cystoprostatectomy = 22), usually with lymphadenectomy (n = 40). Curative radiotherapy (RT) was delivered in 32 patients, as radical (n = 5), neoadjuvant (n = 10), or postoperative treatment (n = 17). Eighteen patients received chemotherapy. None of the patients received hormonal therapy., Results: Median follow-up was 72 months (95%CI: 55-not reached). Five-year local control (LC), overall survival (OS), cancer-specific survival, disease-free survival, and metastases-free rates were 47%, 53%, 56%, 35%, and 35%, respectively. Notably, curative RT (neoadjuvant, adjuvant, or definitive) was associated with improved 5-year LC (55% vs. 31%, P = 0.02) and OS (59% vs. 46%, P = 0.1). Surgically treated patients presenting with a cT3-4 tumor (n = 31), who received RT (n = 24), had a significantly improved 5-year LC (68% vs, 33%, P = 0.004) and OS (65% vs. 21%, P < 0.001) rates compared to patients not receiving RT. cT4 patients demonstrated a significantly lower 5-year OS (43% vs. 61%, P = 0.006) and LC (29% vs. 69%, P < 0.001) rates. Histologic subtype was not associated with LC and OS, but patients with prostatic stromal sarcoma, rhabdomyosarcoma, or sarcomatoid carcinoma had worse 5-year LC compared to other types (47% vs. 55%) and OS (49% vs. 58%)., Conclusion: Adult PS has a poor prognosis. Locally advanced tumors have poor LC and OS rates. Curative RT should be considered part of the multidisciplinary approach to PS., (© 2017 Wiley Periodicals, Inc.)

Background: The prevalence of patients with gastrointestinal stromal tumourgst (GIST) who fail currently available treatments imatinib and sunitinib (third-line treatment-eligible GIST) is unknown, but is expected to be below an ultra-orphan disease threshold of 2/100,000 population used in England and Wales. Our study was designed to estimate the prevalence and absolute number of UK patients with unresectable/metastatic GIST at first-, second- and eventually third-line treatment., Methods: Our open population model estimates the probability that the prevalence of UK third-line treatment-eligible GIST patients will remain under the ultra-orphan disease threshold. Model parameters for incidence, proportion of unresectable/metastatic disease and survival estimates for GIST patients were obtained from a targeted literature review and a UK cancer register. The robustness of the results was checked through differing scenarios taking extreme values of the input parameters., Results: The base-case scenario estimated a prevalence of third-line treatment-eligible GIST of 1/100,000 and a prevalence count of 598 with a 99.9% likelihood of being below the ultra-orphan disease threshold. The extreme scenarios, one-way and probabilistic sensitivity analyses and threshold analysis confirmed the robustness of these results., Conclusions: The prevalence of third-line treatment-eligible GIST is very low and highly likely below the ultra-orphan disease threshold.