Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence (STOMP): Five-year results of a randomized phase II trial.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 10-10 ◽  
Author(s):  
Piet Ost ◽  
Dries Reynders ◽  
Karel Decaestecker ◽  
Valerie Fonteyne ◽  
Nicolaas Lumen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Phase Ii Trials ◽  
Curative Intent ◽  
Free Survival ◽  
Randomized Phase Ii ◽  
Oligometastatic Prostate Cancer ◽  
Significant Difference

10 Background: Multiple randomized phase II trials suggest that metastasis-directed therapy (MDT) for oligometastatic prostate cancer (PCa) improves progression-free survival, but the majority of trials lack longer follow-up. We present the updated 5-year results from the STOMP-trial. Methods: In this multicentre, randomised, phase II study, asymptomatic PCa patients were eligible in case of a biochemical recurrence following primary PCa treatment with curative intent and presenting with up to 3 extracranial on choline PET-CT and a serum testosterone levels > 50 ng/ml. Patients were randomly assigned (1:1) to either surveillance or MDT of all detected lesions. Randomisation was balanced dynamically on two factors: PSA doubling time (≤3 vs. > 3 months) and nodal vs non-nodal metastases. The primary endpoint was androgen deprivation therapy (ADT)-free survival. Castrate resistant prostate cancer-free survival (CRPC) was a secondary endpoint. Tests were performed two-sided; p values less than 0.20 were deemed significant. Results: The 5-year ADT-free survival was 8% for the surveillance group and 34% for the MDT group (Figure 1, hazard ratio 0.57 [80% CI: 0.38-0.84], log-rank p = 0.06). There was no significant difference in effect for the different stratification factors (interaction test). The 5-year CRPC-free survival was 53% for the surveillance group and 76% for the MDT group (hazard ratio 0.62 [80% CI: 0.35−1.09]; log−rank p = 0.27). At a median follow for survival of 5.3 years (IQR 4.3-6.3), the 5-year overall survival was 85%, with 6 out of 14 deaths attributed to prostate cancer. Conclusions: The updated STOMP trial outcomes confirm the earlier reported significant difference in ADT free survival in favor of the MDT group compared to surveillance. Prostate-cancer related mortality is low within the first 5 years of diagnosis of oligorecurrent prostate cancer. Clinical trial information: NCT01558427.

Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial

2018 ◽  
Vol 36 (5) ◽  
pp. 446-453 ◽  
Author(s):  
Piet Ost ◽  
Dries Reynders ◽  
Karel Decaestecker ◽  
Valérie Fonteyne ◽  
Nicolaas Lumen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Specific Antigen ◽  
Phase Iii ◽  
Curative Intent ◽  
Free Survival ◽  
Local Progression ◽  
Randomized Phase Ii

Purpose Retrospective studies suggest that metastasis-directed therapy (MDT) for oligorecurrent prostate cancer (PCa) improves progression-free survival. We aimed to assess the benefit of MDT in a randomized phase II trial. Patients and Methods In this multicenter, randomized, phase II study, patients with asymptomatic PCa were eligible if they had had a biochemical recurrence after primary PCa treatment with curative intent, three or fewer extracranial metastatic lesions on choline positron emission tomography–computed tomography, and serum testosterone levels > 50 ng/mL. Patients were randomly assigned (1:1) to either surveillance or MDT of all detected lesions (surgery or stereotactic body radiotherapy). Surveillance was performed with prostate-specific antigen (PSA) follow-up every 3 months, with repeated imaging at PSA progression or clinical suspicion for progression. Random assignment was balanced dynamically on the basis of two factors: PSA doubling time (≤ 3 v > 3 months) and nodal versus non-nodal metastases. The primary end point was androgen deprivation therapy (ADT)–free survival. ADT was started at symptomatic progression, progression to more than three metastases, or local progression of known metastases. Results Between August 2012 and August 2015, 62 patients were enrolled. At a median follow-up time of 3 years (interquartile range, 2.3-3.75 years), the median ADT-free survival was 13 months (80% CI, 12 to 17 months) for the surveillance group and 21 months (80% CI, 14 to 29 months) for the MDT group (hazard ratio, 0.60 [80% CI, 0.40 to 0.90]; log-rank P = .11). Quality of life was similar between arms at baseline and remained comparable at 3-month and 1-year follow-up. Six patients developed grade 1 toxicity in the MDT arm. No grade 2 to 5 toxicity was observed. Conclusion ADT-free survival was longer with MDT than with surveillance alone for oligorecurrent PCa, suggesting that MDT should be explored further in phase III trials.

Outcome of patients with recurrent/refractory osteosarcoma enrolled in three recent phase II trials: A report from the Children’s Oncology Group.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11530-11530
Author(s):  
Seema Rao ◽  
Ruxu Han ◽  
Mark D. Krailo ◽  
Allen Buxton ◽  
Pooja Hingorani ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Progression Free Survival ◽  
Oncology Group ◽  
Phase Ii Trials ◽  
Free Survival ◽  
Significant Difference ◽  
Measurable Disease ◽  
The Impact

11530 Background: Based on seven prior Phase 2 Children’s Oncology Group (COG) trials, the 4-month event-free survival(EFS) and associated confidence interval for relapsed osteosarcoma with measurable disease according to RECIST was determined to be 12% (95% CI 6 - 19%). Three prospective clinical trials were conducted using this historical benchmark to detect activity defined by an EFS improvement of double the upper confidence interval. This report summarizes the outcome of these studies, describes whether the historical data remains an accurate baseline, and considers implications for future phase II trial study design in relapsed osteosarcoma measurable according to RECIST. Methods: We conducted an analysis of outcome for patients with recurrent/refractory osteosarcoma enrolled in three recent prospective COG phase II trials; AOST1321 (unresected cohort), AOST1322 and AOST1521 that used EFS at 4 months as the primary endpoint. Patients were eligible if they had osteosarcoma that had recurred or become refractory after standard therapy and had measurable disease according to RECIST. We assessed whether risk of an EFS event is modified by age, sex, race/ethnicity, number of prior chemotherapy regimens, or time to first relapse. Results: In each of the three phase II trials (unresected group of AOST1321, AOST1322, AOST1521), the drugs tested (denosumab, eribulin and glembatumumab) were concluded to be not effective due to a failure of the patient populations to meet the prespecified active 4-month progression free survival endpoint. The 4-month EFS for the 57 evaluable patients enrolled on these trials was 7% (95% CI 2 – 16%), similar to the 4-month EFS for 96 patients in the previous seven phase II trials of 12% (95% CI 6 - 19%). The combined EFS at 4 months for all 10 studies is 10% (95% CI 6 – 15%).There was no significant difference in EFS across trials based on age, sex, ethnicity, number of prior treatment regimens, consistent with prior analysis. Data from AOST1321 and AOST1521 were analyzed to determine the impact of time to first recurrence on EFS. Two different quantifications were applied: 1 year or less versus 2 or more years; and 2 years or less versus 3 years or more. Neither categorization was statistically significant. Conclusions: The EFS at 4 months in the three new phase II trials is similar to the previous seven phase II single arm trials. The combined analysis of 153 patients from 10 trials tightens the confidence interval, moving the upper 95% CI to 15%. Modification to future study designs could be considered based on this updated analysis. EFS at 4 months remains a robust primary endpoint. Single-arm trials using this endpoint based on the historical benchmark have accrued rapidly and allowed assessment of multiple novel agents in osteosarcoma. The negative trial results and continued poor outcome highlight the need for new approaches for relapsed osteosarcoma. Clinical trial information: NCT02097238, NCT02470091, NCT02487979.

scholarly journals The efficacy of cytoreductive surgery for oligometastatic prostate cancer: a meta-analysis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Bisheng Cheng ◽  
Shuchao Ye ◽  
Peiming Bai
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Endocrine Therapy ◽  
Cytoreductive Surgery ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Oligometastatic Prostate Cancer ◽  
Significant Difference

Abstract Backgrounds At present, the application of tumor reduction surgery in oligometastatic prostate cancer has aroused extensive discussion among urologists, but clinicians have not reached a consensus on this issue. The purpose of this study was to evaluate the effect of cytoreductive surgery for patients with oligometastatic prostate cancer by meta-analysis. Methods All relevant studies were systematically searched through The Cochrane Library, PubMed, Web of Science, EMBASE, and China Biomedical Literature Database (CBM) up to December 2019. All the previous clinical studies on the comparison of long-term efficacy between the cytoreductive surgery group and the endocrine therapy group were included in the search. The included studies were analyzed using Stata ver.14.0. The research has been registered on PROSPERO website with the registration number of crd42021224316. The relevant registration information can be obtained from the website: https://www.crd.york.ac.uk/prospero. Results The case presentation is as follows: ten studies were identified that met the conclusion criteria. The total number of samples was 804; 449 patients underwent cytoreductive surgery, and 355 patients underwent endocrine therapy, and we conducted a meta-analysis of studies to compare the prognosis of endocrine therapy and cytoreductive surgery for treating prostate cancer. After all the studies were analyzed, we found that between cytoreductive surgery and endocrine therapy, a significant difference existed in overall survival (HR = 0.635, 95% CI 0.443–0.908, P = 0.013), cancer-specific survival (HR = 0.407, 95% CI 0.243–0.681, P = 0.001), and progression-free survival (HR = 0.489, 95% CI 0.315–0.758, P = 0.001), while there were no significant difference in progresses to castration-resistant prostate cancer (HR = 0.859, 95% CI 0.475–1.554, P = 0.616). Conclusion The cytoreductive surgery held advantages in overall survival, cancer-specific survival, and progression-free survival. Therefore, compared with endocrine therapy, cytoreductive surgery could be a more suitable approach in treating oligometastatic prostate cancer.

scholarly journals Population-Based Study of Docetaxel or Abiraterone Effectiveness and Predictive Markers of Progression Free Survival in Metastatic Castration-Sensitive Prostate Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Juan Briones ◽  
Maira Khan ◽  
Amanjot K. Sidhu ◽  
Liying Zhang ◽  
Martin Smoragiewicz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Predictive Factors ◽  
Real World ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Predictive Markers ◽  
Age At Diagnosis ◽  
Free Survival ◽  
Significant Difference

BackgroundBoth Docetaxel (DOC) and Abiraterone (ABI) improve the survival of men with metastatic, castration sensitive prostate cancer (mCSPC). However, the outcome among mCSPC patients is highly variable, while there is a lack of predictive markers of therapeutic benefit. Furthermore, there is limited data on the comparative real-world effectiveness of adding DOC or ABI to androgen deprivation therapy (ADT).MethodsWe conducted a retrospective analysis of 121 mCSPC patients treated at Odette Cancer Centre (Toronto, ON, Canada) between Dec 2014 and Mar 2021 (DOC n = 79, ABI n = 42). The primary endpoint studied was progression free survival (PFS), defined as the interval from start of ADT to either (i) biochemical, radiological, or symptomatic progression, (ii) start of first-line systemic therapy for castration-resistant prostate cancer (CRPC), or (iii) death, whichever occurred first. To identify independent predictive factors for PFS in the entire cohort, a Cox proportional hazard model (stepwise selection) was applied. Overall survival (OS) was among secondary endpoints.ResultsAfter a median follow-up of 39.6 and 25.1 months in the DOC and ABI cohorts, respectively, 79.7% of men in the DOC and 40.5% in the ABI group experienced a progression event. PFS favored the ABI cohort (p = 0.0038, log-rank test), with 78.0% (95%CI 66.4–91.8%) of ABI versus 67.1% (57.5–78.3%) of DOC patients being free of progression at 12 months. In univariate analysis superior PFS was significantly related to older age at diagnosis of mCSPC, metachronous metastatic presentation, low-volume (CHAARTED), and low-risk (LATITUDE) disease, ≥90% PSA decrease at 3 months (PSA90), and PSA nadir ≤0.2 at 6 months. Age (HR = 0.955), PSA90 (HR = 0.462), and LATITUDE risk stratification (HR = 1.965) remained significantly associated with PFS in multivariable analysis. OS at 12 months was 98.7% (96.3–100%) and 92.7% (85.0–100%) in the DOC and ABI groups (p = 0.97), respectively.ConclusionsIn this real-world group of men undergoing treatment intensification with DOC or ABI for mCSPC, we did not find a significant difference in OS, but PFS was favoring ABI. Age at diagnosis of mCSPC, PSA90 at 3 months and LATITUDE risk classification are predictive factors of PFS in men with mCSPC.

scholarly journals Anti-Angiogenic Agents in Management of Sarcoma Patients: Overview of Published Trials

2020 ◽  
Vol 10 ◽  
Author(s):  
Pierre-Yves Cren ◽  
Loïc Lebellec ◽  
Thomas Ryckewaert ◽  
Nicolas Penel
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
Double Blind ◽  
Multikinase Inhibitors ◽  
Randomized Phase Ii ◽  
Phase Iii Trials

We reviewed all fully published clinical trials assessing anti-angiogenic agents in sarcoma patients (last issue, January 13, 2020). Anti-angiogenic macromolecules (e.g., bevacizumab or ombrabulin) provide disappointing results. Many multikinase inhibitors have been assessed with non-randomized phase II trials with limited samples and without stratification according to histological subtypes, therefore interpretation of such trials is very challenging. On the contrary, pazopanib, regorafenib, and sorafenib have been assessed using double-blind placebo-controlled randomized phase II or phase III trials. Compared to placebo, sorafenib demonstrates activity in desmoid-type fibromatosis patients. Based on results of phase 3 trial, pazopanib had obtained approval for treatment of pretreated non-adipocytic soft tissue sarcoma. Regorafenib is currently assessed in several clinical settings and provides significant improvement of progression-free survival in pre-treated non-adipocytic soft tissue sarcoma and in advanced pretreated osteosarcoma. Multikinase inhibitors are a breakthrough in sarcoma management. Many trials are ongoing. Nevertheless, predictive factors are still missing.

scholarly journals Preoperative or Perioperative Docetaxel, Oxaliplatin, and Capecitabine (GASTRODOC Regimen) in Patients with Locally-Advanced Resectable Gastric Cancer: A Randomized Phase-II Trial

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2790
Author(s):  
Manlio Monti ◽  
Paolo Morgagni ◽  
Oriana Nanni ◽  
Massimo Framarini ◽  
Luca Saragoni ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Free Survival ◽  
Peritoneal Lavage Cytology ◽  
Multicenter Phase ◽  
Randomized Phase Ii ◽  
Resectable Gastric Cancer ◽  
Lavage Cytology

Docetaxel associated with oxaliplatin and 5-fluorouracil (FLOT) has been reported as the best perioperative treatment for gastric cancer. However, there is still some debate about the most appropriate number and timing of chemotherapy cycles. In this randomized multicenter phase II study, patients with resectable gastric cancer were staged through laparoscopy and peritoneal lavage cytology, and randomly assigned (1:1) to either four cycles of neoadjuvant chemotherapy (arm A) or two preoperative + two postoperative cycles of docetaxel, oxaliplatin, and capecitabine (DOC) chemotherapy (arm B). The primary endpoint was to assess the percentage of patients receiving all the planned preoperative or perioperative chemotherapeutic cycles. Ninety-one patients were enrolled between September 2010 and August 2016. The treatment was well tolerated in both arms. Thirty-three (71.7%) and 24 (53.3%) patients completed the planned cycles in arms A and B, respectively (p = 0.066), reporting an odds ratio for early interruption of treatment of 0.45 (95% confidence interval (CI): 0.18–1.07). Resection was curative in 39 (88.6%) arm A patients and 35 (83.3%) arm B patients. Five-year progression-free survival (PFS) was 51.2% (95% CI: 34.2–65.8) in arm A and 40.3% (95% CI: 28.9–55.2) in arm B (p = 0.300). Five-year survival was 58.5% (95% CI: 41.3–72.2) and 53.9% (95% CI: 35.5–69.3) (p = 0.883) in arms A and B, respectively. The planned treatment was more frequently completed and was more active, albeit not significantly, in the neoadjuvant arm than in the perioperative group.

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