Improved outcomes in advanced stage uterine carcinosarcoma (mixed mullerian tumor [MMT])

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5518-5518
Author(s):  
D. M. O'Malley ◽  
C. Nagel ◽  
L. A. Cantrell ◽  
L. Havrilesky ◽  
M. Liotta ◽  
...  
Keyword(s):  
Late Stage ◽  
Therapy Group ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Postoperative Treatment ◽  
Treatment Modalities ◽  
Advanced Stage ◽  
Treatment Regimens ◽  
Time To Recurrence ◽  
Stage Iv Disease

5518 Background: There is currently no consensus regarding the management of advanced stage uterine MMT. In an effort to better define postoperative treatment modalities and their associated outcomes, we retrospectively reviewed factors that influence progression and survival. Methods: A retrospective, multi-institution study of women diagnosed from 1997–2007 was performed. Post-operative treatment included either observation (OBS), RT (brachytherapy, whole pelvic, or combination), chemotherapy (CT) alone or with RT (CT+RT). The majority of chemotherapy regimens included carboplatinum/paclitaxel, Ifosfamide/cisplatin, cisplatin/adriamycin, Data collected included time to recurrence, overall survival and sites of recurrence. Statistics included t-test, ANOVA and Kaplan Meier. Results: 119 patients were identified with late stage uterine MMT. 81 had stage III disease and 38 had stage IV disease. The median age at diagnosis was 67 years (range: 30–86). 70 (59%) were Caucasian and 48 (40%) were African-American. 116 (87%) were optimally debulked and their survival further analyzed. 18 (15%) were observed and 9 of these patients recurred. This group had the poorest median progression free survival (PFS) of 3.4 months. The majority (N = 50, 49%) of late stage patients underwent adjuvant CT with a median PFS of 13.3 months and median OS of 15.6 months. Of these patients 33 (66%) recurred. 18 (17 %) patients underwent RT alone with a median PFS of 12.4 months and OS of 14.9 months. 14 (78%) of these patients recurred. 20 patients (19%) underwent a combination of CT and RT and 11 (55%) experienced recurrences . The combination therapy group had the longest median PFS of 14.3 months and OS of 17.2 months (p = 0.27). Conclusions: Chemotherapy had become the standard therapy for advanced stage MMT however the addition of radiation has not been established. Patients diagnosed with advanced stage MMT can achieve long-term DFS in a minority of patients (33%) treated with chemotherapy. We showed that the addition of radiation to adjuvant chemotherapy showed a slight improvement over chemotherapy alone yet the optimal therapy has yet to be defined. This retrospective review highlights the need for prospective trials of new therapeutic agents and treatment regimens for women with advanced stage uterine MMT. No significant financial relationships to disclose.

Treatment Outcomes and Relative Dose Intensity of Chemotherapy in Slovene Patients With Advanced Hodgkin Lymphoma

2022 ◽  
Author(s):  
Samo Rozman ◽  
Nina Ružić Gorenjec ◽  
Barbara Jezeršek Novaković
Keyword(s):  
Hodgkin Lymphoma ◽  
Proportional Hazards ◽  
Stage Iv ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Relative Dose Intensity ◽  
Cox Proportional Hazards Models ◽  
Stage Disease ◽  
Stage Iv Disease

Abstract This retrospective study was undertaken to investigate the association of relative dose intensity (RDI) with the outcome of Hodgkin lymphoma (HL) patients with advanced stage disease receiving ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). A total of 114 HL patients treated between 2004 and 2013 were enrolled for evaluation. RDI calculations were based on a Hryniuk's model. The association of variables with overall survival (OS) and progression-free survival (PFS) was analysed using univariate and multivariate Cox proportional hazards models. The median age of patients was 39 years, majority of patients were males and had stage IV disease. Fifty-four patients received ABVD and 60 received BEACOPP chemotherapy with 24 and 4 deaths, respectively. Patients in BEACOPP group were significantly younger with lower Charlson comorbidity index (CCI) in comparison with ABVD group, making the comparison of groups impossible. In ABVD group, RDI was not significantly associated with OS (p=0.590) or PFS (p=0.354) in a multivariate model where age was controlled. The low number of events prevented the analysis in the BEACOPP group. Patients' age was strongly associated with both OS and PFS: all statistically significant predictors for OS and PFS from univariate analyses (chemotherapy regimen, CCI, RDI) lost its effect in multivariate analyses where age was controlled. Based on our observations, we can conclude that RDI is not associated with the OS or PFS after the age is controlled, neither in all patients combined nor in individual chemotherapy groups.

EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma.

1993 ◽  
Vol 11 (8) ◽  
pp. 1573-1582 ◽  
Author(s):  
W H Wilson ◽  
G Bryant ◽  
S Bates ◽  
A Fojo ◽  
R E Wittes ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Prolonged Exposure ◽  
Oral Prednisone ◽  
Stage Iv ◽  
Dose Intensity ◽  
Primary Treatment ◽  
Treatment Regimens ◽  
Aggressive Lymphomas ◽  
Stage Iv Disease

PURPOSE Based on in vitro evidence that tumor cells are less resistant to prolonged exposure to low concentrations of the natural product class, compared with brief higher concentration exposure, we developed a chemotherapy regimen (etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone [EPOCH]) in which the natural products are administered as a continuous infusion. PATIENTS AND METHODS This is a phase II study of etoposide, vincristine, and doxorubicin, administered as a 96-hour continuous infusion, with intravenous (IV) bolus cyclophosphamide and oral prednisone (EPOCH) in 74 consecutive patients who relapsed from or failed to respond to most of the same drugs administered on a bolus schedule. Patients with aggressive lymphomas who achieved a good response after EPOCH were eligible to undergo bone marrow transplantation. RESULTS Patients with intermediate- or high-grade lymphoma comprised 76% of this series and 77% had stage IV disease. Seventy-one percent had previously received all of the drugs contained in the EPOCH regimen and 92% had received at least four of the drugs. Seventy patients were assessable for response, of whom 19 (27%) achieved a complete remission (CR) and 42 (60%) a partial remission (PR). Among 21 patients who had no response to prior chemotherapy, 15 (71%) responded, but only one achieved a CR. Patients who relapsed from an initial CR had a 100% response rate, with 76% CRs. With a median potential follow-up duration of 19 months, there was a 28% probability of being event-free at 1 year. Toxicity was primarily hematologic with neutropenia during 51% of cycles, but only a 17% incidence of febrile neutropenia. Gastrointestinal, neurologic, and cardiac toxicity were minimal. CONCLUSION EPOCH chemotherapy was well tolerated and highly effective in patients who were resistant to or relapsed from the same drugs administered on a bolus schedule, suggesting that continuous infusion of the natural drug component of this regimen is capable of partially reversing drug resistance and reducing toxicity. Dose-intensity (DI) was > or = that achieved in primary treatment regimens for aggressive lymphomas.

scholarly journals Durable and Complete Response to Herceptin Monotherapy in Patients with Metastatic Gastroesophageal Cancer

2017 ◽  
Vol 10 (3) ◽  
pp. 1098-1104 ◽  
Author(s):  
Brenen P. Swofford ◽  
Tomislav Dragovich
Keyword(s):  
Stage Iv ◽  
Progression Free Survival ◽  
Complete Response ◽  
Developed Countries ◽  
Her2 Overexpression ◽  
Gastroesophageal Cancer ◽  
Her2 Receptor ◽  
Durable Response ◽  
First Line Therapy ◽  
Stage Iv Disease

Gastroesophageal cancer is the sixth leading cause of cancer-related death worldwide. The 2 most common histologies are squamous cell carcinoma and adenocarcinoma, which has seen an increase in incidence correlating with an increase in obesity in developed countries. Gastroesophageal adenocarcinoma has a preponderance to metastasize early, making it a highly lethal cancer with a low 5-year survival rate of ∼15–25%. Therefore, for the majority of patients, treatment focuses on palliation and prolongation of survival. Combination chemotherapy regimens, mostly platinum-based, have only modestly prolonged survival in patients with stage IV disease. Recently, it was discovered that the activation of the HER2 receptor plays an important role in a minority of adenocarcinomas of the distal esophagus and stomach. This introduced the treatment option of trastuzumab (Herceptin), a monoclonal antibody directed at the HER2 receptor, which has demonstrated improvement in overall and progression-free survival as noted in the ToGA trial. Currently, the role of Herceptin therapy beyond first-line therapy and outside of combination regimens is not well established. In this case report we review 2 cases of patients with gastroesophageal cancer, with HER2 overexpression, who achieved a robust response to trastuzumab in combination with chemotherapy and were able to maintain a durable response with maintenance trastuzumab monotherapy.

Limited Benefit Gained From Inferior Vena Cava Filter Insertion In Patients With Advanced-Stage Cancer

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1147-1147
Author(s):  
Asem Mansour ◽  
Yousef Ismael ◽  
Hikmat Abdel-Razeq
Keyword(s):  
Cancer Patients ◽  
Survival Data ◽  
Vena Cava ◽  
Stage Iv ◽  
Stage Iii ◽  
Advanced Stage ◽  
Ivc Filter ◽  
Filter Placement ◽  
Stage Iv Disease ◽  
Filter Insertion

Abstract Introduction Cancer and its treatment are recognized risk factors for venous thromboembolism (VTE). Inferior Vena Cava (IVC) filters are utilized to provide mechanical thromboprophylaxis to prevent pulmonary embolism (PE) or to avoid bleeding from systemic anticoagulation in high risk patients. Patients and Methods This study was performed at a stand-alone, Joint Commission International (JCI)-accredited comprehensive cancer center. Hospital database was searched for all patients discharged with IVC filter insertion. Additionally, the radiology database was queried for cancer patients undergoing IVC filter placement. Results A total of 107 cancer patients; 59 (55.1%) males and 48 (44.9%) females who had their IVC filter inserted and followed up at our institution were included. The mean age (±SD) of the whole group was 50.8 (± 14.2) years. All patients had active cancer; the most common primary sites were gastrointestinal 32 (29.9%), brain 16 (15.0%) lung 13 (12.1%) and gynecological tumors 11 (10.3%). Majority of the patients had advanced-stage disease; out of 86 patients with identifiable TNM stage (Tumor, Node, Metastasis), 81 (94.2%) patients had locally-advanced stage III or metastatic stage IV disease, whereas only 5 (5.8%) had stages I or II disease. During the 6 weeks prior to IVC filter placement, 74 (69.2%) patients were on active anticancer therapy with 45 (42.1%) were on chemotherapy and 7 (6.5%) were on radiotherapy. Nineteen (17.8%) of the patients had surgical intervention for their cancer while only 3 (2.8%) were on hormonal therapy. The remaining 33 (30.8%) patients were on hospice and palliative care service with 18 (16.8%) were already placed “DNR” (Don't Resuscitate). Prior to IVC filter insertion, a diagnosis of DVT was made on 76 (71.0%) patients while 14 (13.1%) had PE; the other 17 (15.9%) had both DVT and PE. Contraindication to anticoagulation was the main indication for IVC filter placement reported in 85 (79.4%), while 18 (16.8%) had their filter inserted because of failure of anticoagulation (had DVT and/or PE while on therapeutic doses of anticoagulation). Other indications included large, free-floating iliocaval thrombus and poor compliance with anticoagulation. Filters were placed utilizing the jugular approach in 86 (80.3%) while 18 (16.8%) had their filter placed through a femoral approach. Complications following IVC filter placement occurred in 14 (13.1%); majority were recurrent DVT in 10 (9.3%), PE in 3 (2.8%) and filter thrombosis in one patient. Following IVC filter insertion, 42 (39.3%) were also anticoagulated; majority (86%) with LMWH (enoxaparin or tinzaparin). Twenty (47.6%) of these anticoagulated patients were considered, at the time of IVC filter insertion, as having a contraindication to anticoagulation. Survival data following IVC filter insertion was available for 100 patients. The median survival for the whole group was 2.39 months (range: 0.03-60.2). The median survival for patients with stage III and IV disease were 7.97 (1.90-17.08) and 1.31 months (0.92-2.20), respectively; p=0.0119; (Figure) Few patients had stage I and II disease (two had stage I while three others had stage II disease) and thus were excluded from survival analysis. Among the 59 patients with stage IV disease for whom survival data was available, 23 (39.0%) survived less than a month, while 40 (67.8%) survived less than three months. Survivals of patients with stage III disease were better with only one out of 20 patients (5.0%) survived less than a month, while 14 (70.0%) survived more than three months. Conclusions Cancer patients with advanced-stage disease may gain little benefit from IVC filter insertion, so disease stage and life expectancy should be taken in consideration prior to filter placement. Disclosures: No relevant conflicts of interest to declare.

Treatment guided by ERCC1, RRM1, and BRCA1 protein expression in patients with advanced-stage NSCLC

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19094-e19094
Author(s):  
B. Han ◽  
J. Shen ◽  
Z. Gao
Keyword(s):  
Protein Expression ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Stage Iiib ◽  
Advanced Stage ◽  
Ecog Performance Status ◽  
Brca1 Protein ◽  
Chemotherapy Group

e19094 Purpose: We investigated whether Treatment Guided by ERCC1,RRM1 and BRCA1 protein expression levels could improve clinical outcomes in Patients With Advanced-Stage NSCLC. Experimental Design: Eligibility: Main inclusion criteria: Stage IV or stage IIIB NSCLC; Eastern Cooperative Oncology Group(ECOG) performance status (PS) 0–1; Measurable disease; Adequate bone marrow, kidney, liver function. Main exclusion criteria: previous NSCLC therapy; Central nervous system metastasis; Requiring immediate intervention or Untreated with radiation within 28 days of study regimen initiation. Previously untreated patients with Stage IV or stage IIIB NSCLC(N=180): Standard chemotherapy group(N=60): Cisplatin 75mg/m2 Day1+Vinorelbine 25mg/m2 Days 1,8 every 28 days; Individualized chemotherapy group (N=120) (ERCC1,RRM1 and BRCA1 protein expression assayed with IHC); Low ERCC1 protein expression subgroup: Cisplatin 75mg/m2 Day1+Vinorelbine 25mg/m2 Days 1,8 every 28 days; High ERCC1 protein subgroup: Vinorelbine 25mg/m2 Days 1,8+Gemcitabine 1250mg/m2 Days 1,8 every 28 days. Description of Current Analysis: ERCC1,RRM1 and BRCA1 protein expression assayed with IHC; Assigned treatment based on ERCC1 protein expression; Primary endpoint: overall response rate; Secondary endpoints: Overall survival (OS), Progression-free survival (PFS). Enrollment progress (As of time Dec-31–2008): See Table . [Table: see text] No significant financial relationships to disclose.

HPV and survival in patients with oropharyngeal squamous cell cancer of the head and neck (OPC) treated with induction chemotherapy followed by chemoradiotherapy (ST) versus chemoradiotherapy alone (CRT): The Dana-Farber experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5582-5582
Author(s):  
Jochen H. Lorch ◽  
Glenn Hanna ◽  
Wei Dai ◽  
Vijaya Thotakura ◽  
Vidya Nair ◽  
...  
Keyword(s):  
Cell Cancer ◽  
Stage Iv ◽  
Clinical Information ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Free Survival ◽  
Group Outcomes ◽  
Hpv Status ◽  
Stage Iv Disease ◽  
Versus Stage

5582 Background: HPV status is a major prognostic marker for survival in patients with OPC. We examined overall survival (OS) and progression free survival (PFS) in patients with OPC and known HPV status treated at Dana-Farber Cancer Institute with ST and CRT between 2002 and 2011. Methods: 280 patients with OPC and known HPV status were identified retrospectively and clinical information was recorded. Results: 174 patients were treated with CRT (124 HPV positive, 50 HPV negative) and 106 patients were treated with ST (77 HPV positive, 29 HPV negative). For all 280 patients, OS and PFS were significantly better for patients who were HPV positive compared to those who were HPV negative. 3 year OS was 89.1% for HPV positive (95% CI, 83.8-94.7) and 70.5% for HPV negative patients (95%CI, 59.9-83%, HR 0.37, p=0.0007). Among HPV positive patients treated with CRT, 13/124 had died at 3 years (OS 88.5%, 95%CI 81.7-95.9) while 13 deaths were recorded among 50 HPV negative patients (OS 72.2%, 95% CI 59.1-88.2, HR 0.38, p=0.011). PFS at 3 years was also significantly better for HPV positive versus HPV negative patients(81.7% vs 58.8%, HR 0.42, p=0.006). In the group treated with ST, outcomes were similar despite a higher rate of stage IV versus stage III disease compared to the group treated with CRT (100% stage IV in ST versus 77% stage IV and 23% stage III disease in CRT group). Three year OS was 89.7% for HPV positive and 68.2% in the HPV negative group (8/77 HPV pos vs 10/29 HPV neg, HR 0.33, p=0.015). PFS was borderline better for HPV positive patients (81% vs 61.7%, HR 0.48, p= 0.058). Conclusions: We present the DFCI experience treating OPC with ST and CRT for patients with known HPV status over one decade.OS and PFS were superior for HPV positive versus HPV negative patients. Outcomes were virtually identical for patients treated with CRT versus ST despite a higher rate of stage IV disease in the ST group. Outcomes for the HPV negative patients in particular were superior compared to the published literature.

Chemosensitivity and clinical features of EML4-ALK-positive patients with advanced non-small cell lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18145-e18145 ◽  
Author(s):  
Jangchul Park ◽  
Chiaki Kondo ◽  
Junichi Shimizu ◽  
Yoshitsugu Horio ◽  
Kimihide Yoshida ◽  
...  
Keyword(s):  
Stage Iv ◽  
Cytotoxic Agents ◽  
Advanced Stage ◽  
Second Line ◽  
First Line ◽  
Treatment Regimens ◽  
Anaplastic Lymphoma ◽  
Alk Inhibitor ◽  
Alk Positive ◽  
Line Setting

e18145 Background: Lung cancers that harbor EML4-ALK can be effectively treated with anaplastic lymphoma kinase (ALK) inhibitors. Recent reports showed that pemetrexed-based therapy might be an effective treatment in patients with ALK-positive NSCLC. However, the efficacy of other regimens is still not known. The purpose of this study is to investigate the clinical characteristics, the efficacy of the cytotoxic chemotherapy in the first and second line setting in EML4-ALK positive NSCLC with advanced stage. Methods: EML4-ALK fusion was screened with RT-PCR and immunohistochemistry. When positive results were obtained with either method, gene rearrangement of ALK was confirmed with fluorescent in-situ hybridization. The clinical efficacy of chemotherapy was evaluated retrospectively. Results: We evaluated 20 EML4-ALK positive patients with advanced stage. Twelve patients were without a history of smoking, and 6 light smokers and 2 smokers. Seventeen (85%) of 20 had stage IV disease. Nine cases were male, and 11 were female. The mean age was 46.3 years (range, 26-79 years). Most of the CT findings at the primary site were masses or nodules, while two cases showed air-space consolidation. In the first line chemotherapy, most of the treatment regimens included carboplatin or cisplatin in combination with one or more therapeutic agents, such as taxans, bevacizumab except one case who was treated only by S-1. In 13 cases which were evaluable, 7/13 (53.8%) had a PR, 4/13 (30.8%) had SD, and 2/13 (15.4%) had PD. The treatment regimens in the second line setting included one therapeutic agent such as docetaxel, pemetrexed, S-1 or an oral ALK inhibitor. Among 10 evaluable cases in the second line setting, 2/10 (20%) had a PR, 5/10 (50%) had SD, and 3/10 (30%) had PD. Two patients who had a PR were all treated by oral ALK inhibitor. Within 7 patients who were treated by cytotoxic agents, none had clinical response. Conclusions: Our study suggests that EML4-ALK positive patients may show relatively favorable response to cytotoxic drug in the first line setting, but low response in the second line setting. These data might be helpful for further clinical trials including EML4-ALK positive patients.

Impact of treatment strategies on local control and survival in uterine carcinosarcomas.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16526-e16526
Author(s):  
Selim Yalcin ◽  
Omer Dizdar ◽  
Nadire Kucukoztas ◽  
Samed Rahatli ◽  
Ozlem Ozen ◽  
...  
Keyword(s):  
Uterine Cancer ◽  
Treatment Strategies ◽  
Stage Iv ◽  
Total Abdominal Hysterectomy ◽  
Abdominal Hysterectomy ◽  
Uterine Carcinosarcoma ◽  
Treatment Regimens ◽  
Stage Iv Disease ◽  
Standardized Treatment

e16526 Background: Carcinosarcoma is a biphasic neoplasm composed of a mixture of malignant epithelial and mesenchymal components. Uterine carcinosarcomas comprise only 3% of all uterine malignancies, however they account for a disproportionally higher rate of mortality from uterine cancer because of their agressive nature. No standardized treatment has yet been established. The purpose of this study was to determine the clinical characteristics, patterns of recurrence and survival outcomes in patients with uterine carcinosarcoma treated in our institution. Methods: Records of the patients with uterine carcinosarcoma were retrospectively evaluated and 29 pts with carcinosarcoma diagnosed between 2007 and 2012 were identified. All patients were initially treated surgically by the same surgeon with comprehensive staging, i.e. total abdominal hysterectomy, bilateral salphingooopherectomy , bilateral pelvic and paraaortic lymph node dissection and omentectomy. Demographic features, tumor characteristics, treatment regimens and patient outcomes in terms of relapse-free survival (RFS) and overall survival (OS) were analyzed. Results: Median age was 63 (range 43-78). 13 patients (45%) had stage I disease, 5 patients (17%) had stage III and 11 patients (38%) had stage IV disease at diagnosis. Median tumor size was 6 cm (range 1.7-20 cm) and lymphovascular invasion was present in 17 patients 59%). Twenty patients (69%) received chemotherapy (90% with paclitaxel and carboplatin) for 6 cycles. One patient received radiotherapy. Median follow up was 13 mos. Seventeen patients (59%) relapsed and 20 patients (69%) died on follow up. Two patients had vaginal cuff recurrence, 4 had pelvic, 4 had abdominal and 7 had distant recurrences. All recurrences were fatal. 3 year RFS was 31%. 3 year OS was 15%. Conclusions: Our data show that uterine carcinosarcomas tend to be more at more advanced stage at diagnosis and despite the use of chemotherapy and radiotherapy, overall prognosis is poor. Surgery remains the mainstay of treatment. More effective adjuvant strategies are needed to reduce relapse and death rates because recurrences are generally fatal.

Association of FDG PET-CT (PET) avid skeletal lesions (SL) with progression-free survival (PFS) in patients (pts) with previously untreated follicular lymphoma (FL).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19026-e19026
Author(s):  
Joseph J. Maly ◽  
Lai Wei ◽  
Jessica Hemminger ◽  
Beth Christian ◽  
Kami J. Maddocks ◽  
...  
Keyword(s):  
Bone Marrow Involvement ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Single Center ◽  
Bulky Disease ◽  
Therapeutic Trials ◽  
Increased Risk ◽  
Pet Ct ◽  
Stage Iv Disease ◽  
Fdg Pet Ct

e19026 Background: PET scan is frequently utilized in FL. Reduced EFS has been observed in DLBCL pts with SL treated with RCHOP (Held, JCO 31:4115, 2013). Methods: We performed a retrospective single center study to assess outcomes of FL pts with PET avid SL between January 2005 and November 2015. 131 pts with newly diagnosed FL and PET performed within 1 month of diagnosis were included. Results: 32 of these pts had SL (median 4, range 1-11) on initial PET. Median age was 57 (range 43-79), 15 (47%) were female, 30 (94%) had stage IV disease, LDH was elevated in 6 (19%), 6 (19%) had bulky disease > 6 cm, and FLIPI-1 score was low in 5, intermediate in 11, and high 16 pts. 27 pts had grade (gr) 1-2 FL, 2 had gr 3a, and 3 had gr 3 (not classified). All but 1 patient received rituximab (R)-containing therapy (9 received BR, 7 received RCHOP, 5 RCVP, 9 other). 8 pts received maintenance R, and none received radiation. There were no statistically significant differences in median age, tumor gr, LDH, or use of anthracycline containing therapy (28% in SL group vs 16% in non-SL group, p = 0.13) in pts with SL compared to those without SL (n = 99). Pts with SL had higher incidence of bone marrow involvement (27% vs 9%, p = 0.013). With a median follow-up of 35 months, SL pts had 44% rate of transformation to DLBCL compared 12% in non-SL pts (p = 0.004). Median PFS was 45.8 months in SL pts not-reached in non-SL pts (p = 0.003). Median OS was 105.9 months in SL pts and not reached in non-SL pts (p = 0.08). In the multi-variate analysis, SL (p = 0.037), male gender (p = 0.048), higher FLIPI-1 score (p = 0.009), and absence of anthracycline containing therapy (p = 0.005) were significantly associated with decreased PFS using backward selection. Conclusions: The presence of PET identified SL in previously untreated FL is associated with an increased risk of transformation and reduced PFS in this single center retrospective analysis. Larger studies of uniformly treated pts are needed to validate these data. The identification of high-risk PET avid SL in FL pts in future prospective therapeutic trials could be used to select pts for specific induction regimens, maintenance rituximab, or consolidative radiation.

FORT-1: Phase II/III study of rogaratinib versus chemotherapy (CT) in patients (pts) with locally advanced or metastatic urothelial carcinoma (UC) selected based on FGFR1/3 mRNA expression.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 489-489 ◽  
Author(s):  
David I. Quinn ◽  
Daniel Peter Petrylak ◽  
Joaquim Bellmunt ◽  
Andrea Necchi ◽  
Howard Gurney ◽  
...  
Keyword(s):  
Phase Ii ◽  
Locally Advanced ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Open Label ◽  
Activating Mutations ◽  
Stage Iv Disease ◽  
Dna Alterations ◽  
Grade 3 ◽  
Muscle Invasive

489 Background: Aberrant activation of fibroblast growth receptor (FGFR) signaling plays a role in UC. Rogaratinib, a pan-FGFR1-4 inhibitor, has promising efficacy and safety in pts with advanced muscle-invasive UC, selected based on FGFR1-3 mRNA overexpression and/or FGFR3-activating mutations/translocations. This Phase II/III, randomized, open-label study evaluated the efficacy of rogaratinib vs CT in pts with FGFR-positive advanced or metastatic UC who received prior platinum CT. We present an ORR analysis for rogaratinib vs CT. Methods: FGFR1/3 mRNA was tested by in situ hybridization of archival tissue. Pts were randomized 1:1 to 800 mg rogaratinib p.o. BID continuously or CT Q3W (i.v., docetaxel 75 mg/m2, paclitaxel 175 mg/m2, or vinflunine 320 mg/m2), and stratified by PIK3CA/ RAS-activating mutations, prior immunotherapy, and modified 4-factor Bellmunt risk score. Results: 87 pts were assigned to rogaratinib and 88 to CT. Overall, 82.9% were male, median age was 69.0 yrs (range: 36-89), 96.6% had stage IV disease, and 2.3% were stage IIIB. PIK3CA/ RAS-activating mutations were present in 11.4% of pts. ORRs of 19.5% and 19.3% (1-sided p=0.56) and disease control rates of 49.4% and 55.7% (p=0.84) were observed for rogaratinib and CT, respectively; median progression-free survival was 2.7 months (95% CI 1.6, 4.2) and 2.9 months (95% CI 2.6, 4.2). Grade 3-4 treatment-emergent adverse events occurred in 40/86 pts (47%) treated with rogaratinib and 46/82 pts (56%) with CT, most commonly anemia (3% vs 15%), neutropenia (1% vs 17%), asthenia (9% vs 1%), lipase increase (8% vs 2%), fatigue (2% vs 6%), and urinary tract infection (2% vs 6%). Exploratory analysis of pts with FGFR3 DNA alterations (4 spot mutations and fusions) showed ORRs of 52.4% with rogaratinib and 26.7% with CT. Conclusions: In pts with FGFR1/3 tumor mRNA-positive UC, rogaratinib had efficacy comparable with standard CT and an acceptable safety profile. Subgroup analysis suggests rogaratinib may be more active in pts with an FGFR3 DNA alteration. Sensitivity analysis of biomarker subgroups is ongoing. Clinical trial information: NCT03410693.

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