scholarly journals Historical time to disease progression and progression‐free survival in patients with recurrent/refractory neuroblastoma treated in the modern era on Children's Oncology Group early‐phase trials

Cancer ◽  
2017 ◽  
Vol 123 (24) ◽  
pp. 4914-4923 ◽  
Author(s):  
Wendy B. London ◽  
Rochelle Bagatell ◽  
Brenda J. Weigel ◽  
Elizabeth Fox ◽  
Dongjing Guo ◽  
...  
Keyword(s):  
Disease Progression ◽  
Early Phase ◽  
Progression Free Survival ◽  
Historical Time ◽  
Oncology Group ◽  
Free Survival ◽  
Early Phase Trials ◽  
Modern Era

scholarly journals A multicenter phase II randomized trial of durvalumab (MEDI-4736) versus physician’s choice chemotherapy in recurrent ovarian clear cell adenocarcinoma (MOCCA)

2020 ◽  
Vol 30 (8) ◽  
pp. 1239-1242
Author(s):  
Natalie YL Ngoi ◽  
Valerie Heong ◽  
Samuel Ow ◽  
Wen Yee Chay ◽  
Hee Seung Kim ◽  
...  
Keyword(s):  
Sample Size ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Immune Checkpoint ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Progression Free Survival ◽  
Oncology Group ◽  
Ovarian Clear Cell Carcinoma ◽  
Free Survival

BackgroundThe optimal treatment of recurrent ovarian clear cell carcinoma remains unknown. There is increasing rationale to support the role of immune checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis in ovarian clear cell carcinoma.Primary objectiveTo evaluate the efficacy of durvalumab (MEDI-4736) compared with standard chemotherapy in patients with recurrent ovarian clear cell carcinoma.Study hypothesisPatients with recurrent ovarian clear cell carcinoma treated with durvalumab will have improved progression-free survival compared with those treated with chemotherapy of physician’s choice.Trial designThe MOCCA study is a multicenter, open-label, randomized phase II trial in patients with recurrent ovarian clear cell carcinoma, which recruited from eight sites across Gynecologic Cancer Group Singapore (GCGS), Korean Gynecologic-Oncology Group (KGOG), and Australia New Zealand Gynecological Oncology Group (ANZGOG). Enrolled patients were randomized in a 2:1 ratio to receive durvalumab or physician’s choice of chemotherapy until disease progression, intolerable toxicity, or withdrawal of patient consent.Major inclusion/exclusion criteriaEligible patients required histologically documented diagnosis of recurrent ovarian clear cell carcinoma, as evidenced by WT1 negativity. All patients must have been of Eastern Cooperative Oncology Group (ECOG) performance status 2 or better, and have had previous treatment with, and progressed or recurred after prior platinum-based chemotherapy. No more than four prior lines of treatment were allowed and prior immune checkpoint inhibitor treatment was not permitted.Primary endpointsThe primary endpoint was the median progression-free survival following treatment with durvalumab, compared with physician’s choice of chemotherapy. Progression-free survival was defined as the time from the first day of treatment to the first observation of disease progression, or death due to any cause, or last follow-up.Sample sizeThe target sample size was 46 patients.Estimated dates for completing accrual and presenting resultsAccrual has been completed and results are expected to be presented by mid-2021.Trial registrationClinicaltrials.gov: NCT03405454.

Treatment exceeds expectations with vemurafenib monotherapy in a patient with BRAFV600E-mutant metastatic melanoma

2020 ◽  
Vol 26 (7) ◽  
pp. 1754-1758
Author(s):  
Mesut Yilmaz ◽  
Şermin Güven Meşe
Keyword(s):  
Metastatic Melanoma ◽  
Poor Prognosis ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Complete Response ◽  
Braf Inhibitors ◽  
Free Survival ◽  
Therapy Options ◽  
Modern Era ◽  
Braf Mutant

Introduction Patients with distant metastatic melanoma has a poor prognosis, with a reported median survival time of six to eight months. In modern era, survival has prolonged with the immunotherapy and targeted therapy options. Potent and selective BRAF inhibitors have been developed that specifically inhibit mutated BRAF over other RAF kinases. Vemurafenib was the first selective tyrosine kinase inhibitor developed to target the V600E allele of BRAF-mutant melanoma. Case Report In this report, we present a case of BRAFV600E-mutant metastatic melanoma, which is being treated with vemurafenib monotherapy with complete response for about seven years. Management and Outcome The patient is still being treated with vemurafenib and radiologic complete response is ongoing for about seven years. Discussion Patients treated with BRAF inhibitors monotherapy had promising response rates and improvement in the progression-free survival and overall survival, but melanoma cells became resistant very quickly, affecting the progression. In this case, we present a case that has permanent response to vemurafenib monotherapy.

scholarly journals Blood Cadmium Level Is Associated with Short Progression-Free Survival in Nasopharyngeal Carcinoma

2019 ◽  
Vol 16 (16) ◽  
pp. 2952 ◽  
Author(s):  
Taifeng Du ◽  
Wenlong Huang ◽  
Shukai Zheng ◽  
Mian Bao ◽  
Yuanni Huang ◽  
...  
Keyword(s):  
Risk Factor ◽  
Disease Progression ◽  
Progression Free Survival ◽  
Cadmium Exposure ◽  
Smoking History ◽  
Cadmium Level ◽  
Clinical Factors ◽  
Free Survival ◽  
Kaplan Meier ◽  
Blood Cadmium

The prognosis of nasopharyngeal carcinoma (NPC) is poor with disease progression. Cadmium exposure is a risk factor for NPC. We aimed to investigate the effect of cadmium exposure, by measuring cadmium level, and clinicopathologic factors on NPC disease progression and prognosis. A total of 134 NPC cases were analyzed and venous blood samples were collected. Blood cadmium level was analyzed by graphite furnace atomic absorption spectrophotometry. Clinical data were collected at baseline for patients and tumor characteristics from medical records. Progression-free survival (PFS) was analyzed during follow-up. The effect of cadmium exposure and clinical factors on PFS was analyzed by the Kaplan–Meier method and Cox regression models. Blood cadmium level was associated with history of disease and smoking history and pack-years. On Kaplan–Meier analysis, a high blood cadmium level, male sex, smoking history and increasing pack-years, as well as advanced clinical stage were all associated with short PFS. On multivariate analysis, blood cadmium level was an independent risk factor and predictor of NPC prognosis and disease progression. Cadmium exposure and related clinical factors can affect the prognosis of NPC, which merits further study to clarify.

Progression-Free Survival in Children With Optic Pathway Tumors: Dependence on Age and the Quality of the Response to Chemotherapy—Results of the First French Prospective Study for the French Society of Pediatric Oncology

2003 ◽  
Vol 21 (24) ◽  
pp. 4572-4578 ◽  
Author(s):  
Véronique Laithier ◽  
Jacques Grill ◽  
Marie-Cécile Le Deley ◽  
Marie-Madeleine Ruchoux ◽  
Dominique Couanet ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Disease Progression ◽  
Objective Response ◽  
Progression Free Survival ◽  
Optic Pathway ◽  
Free Survival ◽  
Factors Associated ◽  
Response To Chemotherapy ◽  
Risk Of Disease

Purpose: To evaluate a strategy aimed at avoiding radiotherapy during first-line treatment of children with progressive optic pathway tumors (OPT), by exclusively administering multiagent chemotherapy during 16 months. Patients and Methods: Between 1990 and 1998, 85 children with progressive OPT were enrolled onto this multicenter nationwide trial. Chemotherapy alternating procarbazine plus carboplatin, etoposide plus cisplatin, and vincristine plus cyclophosphamide was given every 3 weeks. At the time of relapse or progression, second-line chemotherapy was authorized before recourse to radiotherapy. Results: Objective response rate (partial response [PR] + complete response [CR]) to chemotherapy was 42%. Five-year progression-free survival (PFS) and overall survival rates were 34% and 89%, respectively. The 5-year radiotherapy-free survival rate was 61%. In the multivariate analysis of the 85 patients that entered onto the study, factors associated with the risk of disease progression were age younger than 1 year at diagnosis (P = .047) and absence of neurofibromatosis type 1 (P = .035). In the multivariate analysis of the 74 patients that remained on study after the first cycle of chemotherapy, factors associated with the risk of disease progression were age younger than 1 year at diagnosis (P = .0053) and no objective response to chemotherapy (P = .0029). Three-year PFS was 44% in infants ≤ 1 year versus 66% in children older than 1 year. Three-year PFS was 53% in the absence of an objective response to chemotherapy versus 68% after a PR or CR. Conclusion: A significant proportion of children with OPT can avoid radiotherapy after prolonged chemotherapy. Deferring irradiation with chemotherapy protocols did not compromise overall survival of the entire population or visual function.

scholarly journals Application of Circulating Cell-Free Tumor DNA Profiles for Therapeutic Monitoring and Outcome Prediction in Genetically Heterogeneous Metastatic Melanoma

2019 ◽  
pp. 1-10 ◽  
Author(s):  
Renáta Váraljai ◽  
Kilian Wistuba-Hamprecht ◽  
Teofila Seremet ◽  
Joey Mark S. Diaz ◽  
Jérémie Nsengimana ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Metastatic Melanoma ◽  
Disease Progression ◽  
Progression Free Survival ◽  
Mitogen Activated Protein Kinase ◽  
Quantitative Detection ◽  
Early Assessment ◽  
Free Survival ◽  
Mitogen Activated Protein ◽  
Tumor Dna

PURPOSE Circulating cell-free tumor DNA (ctDNA) reflects the heterogeneous spectrum of tumor-specific mutations, especially in systemic disease. We validated plasma-based assays that allow the dynamic quantitative detection of ctDNA as a prognostic biomarker for tumor load and prediction of therapy response in melanoma. MATERIALS and METHODS We analyzed plasma-derived ctDNA from a large training cohort (n = 96) of patients with advanced-stage melanoma, with assays for the BRAFV600E and NRASQ61 driver mutations as well as TERTC250T and TERTC228T promoter mutations. An independent patient cohort (n = 35) was used to validate the utility of ctDNA monitoring under mitogen-activated protein kinase–targeted or immune checkpoint therapies. RESULTS Elevated plasma ctDNA level at baseline was an independent prognostic factor of disease progression when compared with serum S100 and lactate dehydrogenase levels in multivariable analyses (hazard ratio [HR], 7.43; 95% CI, 1.01 to 55.19; P = .05). The change in ctDNA levels during therapy correlated with treatment response, where increasing ctDNA was predictive for shorter progression-free survival (eg, for BRAFV600E ctDNA, HR, 3.70; 95% CI, 1.86 to 7.34; P < .001). Increasing ctDNA levels predicted disease progression significantly earlier than did routine radiologic scans ( P < .05), with a mean lead time of 3.5 months. NRAS-mutant ctDNA was detected in a significant proportion of patients with BRAF-mutant tumors under therapy, but unexpectedly also at baseline. In vitro sensitivity studies suggested that this represents higher-than-expected intratumoral heterogeneity. The detection of NRASQ61 ctDNA in baseline samples of patients with BRAFV600E mutation who were treated with mitogen-activated protein kinase inhibitors significantly correlated with shorter progression-free survival (HR, 3.18; 95% CI, 1.31 to 7.68; P = .03) and shorter overall survival (HR, 4.08; 95% CI, 1.57 to 10.58; P = .01). CONCLUSION Our results show the potential role of ctDNA measurement as a sensitive monitoring and prediction tool for the early assessment of disease progression and therapeutic response in patients with metastatic melanoma.

Prognostic factors of ado-trastuzumab emtansine treatment in patients with metastatic HER-2 positive breast cancer

2020 ◽  
pp. 107815522092408 ◽  
Author(s):  
Deniz Tataroglu Ozyukseler ◽  
Mustafa Basak ◽  
Seval Ay ◽  
Aygül Koseoglu ◽  
Serdar Arıcı ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Trastuzumab Emtansine ◽  
Oncology Group ◽  
Cancer Antigen ◽  
Free Survival

Background Ado-trastuzumab emtansine is an antibody-drug conjugate that combines the cytotoxic activity of emtansine with human epidermal growth factor receptor 2-targeted antitumor features of trastuzumab. Objective We conducted a study of metastatic breast cancer patients treated with trastuzumab emtansine. By evaluating progression-free survival, overall survival, and response rates, we aimed to find prognostic factors of trastuzumab emtansine treatment. Methods Our study is a single-center, retrospective, observational study. We have clinical data from 78 patients treated with trastuzumab emtansine for metastatic breast cancer, from May 2016 through May 2019, at Kartal Dr Lutfi Kirdar Education and Research Hospital, Medical Oncology Department. Our objective is to assess the survival and response rates in trastuzumab emtansine-treated individuals and the factors associated with survival. The factors we analyzed were cancer antigen 15-3 sensitivity, Eastern Cooperative Oncology Group-Performance Status, presence or absence of visceral metastases, presence or absence of cranial metastases, and treatment-associated thrombocytopenia. Results Among 78 patients, median progression-free survival was 7.8 months, and overall survival was 21.1 months. Twenty of the patients had an objective tumor response. The results showed that trastuzumab emtansine was tolerable with a manageable safety profile and consistent with the results of the previous literature. Mostly seen adverse events were anemia, thrombocytopenia, fatigue, and increased levels of alkaline phosphatase. Patients with Eastern Cooperative Oncology Group-Performance Status = 2 had worse progression-free survival and overall survival compared to ones with Eastern Cooperative Oncology Group-Performance Status < 2; progression-free survival and overall survival are worse in cancer antigen 15-3-sensitive breast cancer patients. According to our findings, treatment-associated thrombocytopenia was a significant prognostic factor for survival. Patients with thrombocytopenia had 12 months progression-free survival, whereas patients without thrombocytopenia had only 4.1 months progression-free survival. In like manner, overall survival was much better in the thrombocytopenia-experienced patients as 29.5 versus 11.8 months. Conclusions Trastuzumab emtansine prolongs progression-free survival and overall survival with a manageable safety profile. Thrombocytopenia, Eastern Cooperative Oncology Group-Performance Status, and cancer antigen 15-3 are correlated with progression-free survival and/or overall survival.

scholarly journals Molecular profiling of advanced solid tumours. The impact of experimental molecular-matched therapies on cancer patient outcomes in early-phase trials: the MAST study

2021 ◽  
Author(s):  
Valentina Gambardella ◽  
Pasquale Lombardi ◽  
Juan Antonio Carbonell-Asins ◽  
Noelia Tarazona ◽  
Juan Miguel Cejalvo ◽  
...  
Keyword(s):  
Early Phase ◽  
Progression Free Survival ◽  
Tumor Board ◽  
Prior Therapy ◽  
Early Phase Trials ◽  
Molecular Tumor Board ◽  
Early Phase Clinical Trials ◽  
The Impact ◽  
To Receive

Abstract Introduction Molecular-matched therapies have revolutionized cancer treatment. We evaluated the improvement in clinical outcomes of applying an in-house customized Next Generation Sequencing panel in a single institution. Methods Patients with advanced solid tumors were molecularly selected to receive a molecular-matched treatment into early phase clinical trials versus best investigators choice, according to the evaluation of a multidisciplinary molecular tumor board. The primary endpoint was progression-free survival (PFS) assessed by the ratio of patients presenting 1.3-fold longer PFS on matched therapy (PFS2) than with prior therapy (PFS1). Results Of a total of 231 molecularly screened patients, 87 were eligible for analysis. Patients who received matched therapy had a higher median PFS2 (6.47 months; 95% CI, 2.24–14.43) compared to those who received standard therapy (2.76 months; 95% CI, 2.14–3.91, Log-rank p = 0.022). The proportion of patients with a PFS2/PFS1 ratio over 1.3 was significantly higher in the experimental arm (0.33 vs 0.08; p = 0.008). Discussion We demonstrate the pivotal role of the institutional molecular tumor board in evaluating the results of a customized NGS panel. This process optimizes the selection of available therapies, improving disease control. Prospective randomized trials are needed to confirm this approach and open the door to expanded drug access.

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