Factors affecting survival of patients with Masaoka stage IV thymic epithelial tumors (TET).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7107-7107
Author(s):  
Yaman Suleiman ◽  
Milan Radovich ◽  
Luis Rojas ◽  
Ryan Frederick Porter ◽  
Madison Conces ◽  
...  
Keyword(s):  
De Novo ◽  
Residual Disease ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Primary Treatment ◽  
Lung Nodules ◽  
Thymic Epithelial Tumors ◽  
Masaoka Stage ◽  
Pleural Metastasis ◽  
Stage Iv Disease

7107 Background: Thymoma and thymic carcinoma (TC) are rare tumors, but represent the most common neoplasms of the anterior mediastinum. The vast majority of TET present in early stages with little data existing on factors influencing survival in patients with advanced or stage IV disease. Methods: A retrospective analysis was performed on patients with confirmed TET (histology and with tissue blocks) seen at IUSCC diagnosed between 1976 and 2011. Patient demographics including Masaoka stage, histology, and sites of metastasis were linked with progression free survival (PFS) and overall survival (OS). Results: Our analysis included 102 patients with stage IV TET: 50 presented de novo and 52 developed stage IV disease following primary treatment. When stratified by tumor histology (thymoma or TC), patients with TC had considerably poorer PFS (p=1.87x10-7) and OS (p=7.72x10-8). The median PFS for TC was 13 months (range 4 to 39) and the MST was 36 months (range 4 to 115). PFS at 5-years was 21% and 0% but the five-year OS was 84% and 29% for thymoma and TC, respectively. Ten year OS was 55% for patients with thymoma and 0% for those with TC. Pleural (>3 vs. <3) metastases were significantly associated with a better PFS (p=0.036) and OS (p=0.0003). The PFS and OS of patients with lung nodules trended with those with pleural metastasis. Patients with pleural metastasis and lung nodules sites did considerably better than those with visceral disease (PFS, p=0.004, OS, p=2.09x10-5). Conclusions: Patients with TC have significantly poorer PFS and OS when compared to thymoma confirming that TC is a distinct clinical entity from thymoma. Patients with thymoma may have prolonged survival, despite having residual disease. Although current staging places patients with pleural metastasis (Masaoka stage IVA) and those with lung nodules (stage IVB) as separate categories, our data would suggest that those with lung nodules have similar survival with those who have pleural metastasis.

Pan-cancer evaluation of homologous repair deficiency somatic mutations and response to first-line anti-neoplastic therapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10535-10535
Author(s):  
Jessica A Lavery ◽  
Samantha Brown ◽  
Gregory J. Riely ◽  
Philippe L. Bedard ◽  
Ben Ho Park ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
De Novo ◽  
Stage Iv ◽  
Progression Free Survival ◽  
First Line ◽  
Major Mechanism ◽  
First Line Therapy ◽  
Oncogenic Mutation ◽  
Line Therapy ◽  
Response To Chemotherapy

10535 Background: Homologous recombination is a major mechanism of defective DNA repair, but it remains uncertain whether homologous repair deficient (HRD) tumors have favorable prognosis or are more/less likely to respond to treatment than tumors lacking such mutations. Objective: To determine whether lung (NSCLC) and colorectal (CRC) HRD+ tumors have better survival or response to chemotherapy than HRD- tumors. Methods: Patients with de novo stage IV NSCLC or CRC who had next generation sequencing (NGS) between 2015-2018 from one of four cancer centers were identified. Records were curated using the PRISSMM framework to ascertain treatment, overall survival (OS) and progression free survival based on imaging (PFS-I) and oncologists’ notes (PFS-M). Each NSCLC or CRC tumor was categorized as HRD+ if NGS revealed an oncogenic/likely oncogenic mutation in: ATM, BAP1, BARD1, BLM, BRCA1, BRCA2, BRIP1, CHEK2, FAM175A, FANCA, FANCC, NBN, PALB2, RAD50, RAD51, RAD51C, RTEL1, or MRE11A based on the OncoKB database. The tumor was categorized as HRD- if no oncogenic mutation in any of these genes was evident and HRD indeterminate (HRD?) if no mutation was identified but the panel did not include all genes. OS, PFS-I and PFS-M from start of first line therapy were reported by HRD status. The percentage with a good response to first line therapy (≥2x the median) and exceptional response (≥3x the median) was estimated for each endpoint. Results: For NSCLC 4% were HRD+, 59% HRD- and 37% HRD?. For CRC there were 5% HRD+, 60% HRD- and 35% HRD?. There were no significant differences for any survival endpoint between patients who were HRD+ vs HRD- in univariable analyses. The proportion of good and exceptional responders to first line systemic chemotherapy also did not vary by HRD status, though patients with HRD+ CRC were potentially more likely to be exceptional responders. Similarly, no differences between HRD+ and HRD- tumors were apparent for the subgroup receiving platinum containing therapy. Conclusions: NSCLC and CRC patients with somatic mutations in HRD oncogenic genes did not differ from patients lacking such a mutation with respect to OS or PFS. CRC patients with HRD+ tumors may be more likely to be exceptional responders, but sample sizes are limited. By May, the analysis will include breast and pancreatic cancer cases.[Table: see text]

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 Spending for Advanced Cancer Diagnoses: Comparing Recurrent Versus De Novo Stage IV Disease

2019 ◽  
Vol 15 (7) ◽  
pp. e616-e627 ◽  
Author(s):  
Michael J. Hassett ◽  
Matthew Banegas ◽  
Hajime Uno ◽  
Shicheng Weng ◽  
Angel M. Cronin ◽  
...  
Keyword(s):  
Advanced Cancer ◽  
Cancer Diagnosis ◽  
De Novo ◽  
Stage Iv ◽  
Absolute Difference ◽  
Medicare Data ◽  
Stage Iv Disease ◽  
De Novo Cancer ◽  
Payment Models ◽  
Diagnosis Age

PURPOSE: Spending for patients with advanced cancer is substantial. Past efforts to characterize this spending usually have not included patients with recurrence (who may differ from those with de novo stage IV disease) or described which services drive spending. METHODS: Using SEER-Medicare data from 2008 to 2013, we identified patients with breast, colorectal, and lung cancer with either de novo stage IV or recurrent advanced cancer. Mean spending/patient/month (2012 US dollars) was estimated from 12 months before to 11 months after diagnosis for all services and by the type of service. We describe the absolute difference in mean monthly spending for de novo versus recurrent patients, and we estimate differences after controlling for type of advanced cancer, year of diagnosis, age, sex, comorbidity, and other factors. RESULTS: We identified 54,982 patients with advanced cancer. Before diagnosis, mean monthly spending was higher for recurrent patients (absolute difference: breast, $1,412; colorectal, $3,002; lung, $2,805; all P < .001), whereas after the diagnosis, it was higher for de novo patients (absolute difference: breast, $2,443; colorectal, $4,844; lung, $2,356; all P < .001). Spending differences were driven by inpatient, physician, and hospice services. Across the 2-year period around the advanced cancer diagnosis, adjusted mean monthly spending was higher for de novo versus recurrent patients (spending ratio: breast, 2.39 [95% CI, 2.05 to 2.77]; colorectal, 2.64 [95% CI, 2.31 to 3.01]; lung, 1.46 [95% CI, 1.30 to 1.65]). CONCLUSION: Spending for de novo cancer was greater than spending for recurrent advanced cancer. Understanding the patterns and drivers of spending is necessary to design alternative payment models and to improve value.

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.

A Prospective, Randomised Trial of Chlorambucil, Mitoxantrone and Dexamethasone (CMD) Versus Fludarabine, Mitoxantrone and Dexamethasone (FMD) for Advanced Follicular Lymphoma (Real Grades I-III, Stages III/IV).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 534-534
Author(s):  
Andrew Haynes ◽  
Andrew McMillan ◽  
Andrew Jack ◽  
Wendi Qian ◽  
Ira Jakupovic ◽  
...  
Keyword(s):  
De Novo ◽  
Bone Marrow Failure ◽  
Randomised Trial ◽  
Stage Iv ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Low Grade ◽  
Inadequate Response ◽  
End Points ◽  
Prospective Randomised Trial

Abstract Fludarabine, alone and in combination, has activity in de novo and relapsed/refractory follicle centre cell lymphoma (FCCL), as do many other combinations of chemotherapy, including chlorambucil, mitoxantrone and steroids. In this multicentre study, between May 2000 and April 2006, 400 adults with FCCL (REAL grades I-III) were randomised to receive either CMD (chlorambucil 10mgs po, od, days 1–10, mitoxantrone 12mgs/m2 IV, day 1 and dexamethasone 20mgs po, od, days 1–5) or FMD (fludarabine 25mgs/m2, IV days 1–3, with M and D as for CMD) on physicians’ decision to treat advanced stage (III or IV) disease (B symptoms, bone marrow failure, bulk or progression and compression syndromes). Rituximab (R) was not available for this trial. Randomisation was prospectively stratified by IPI score. Patients received four courses before assessment of response, then had no further trial therapy with progression or inadequate response or had a maximum total of eight courses if responding. The primary end points were progression-free survival (PFS) and overall survival (OS) and the secondary end points were complete (C) and partial (P) remission rates (RR). This preliminary report is at median follow-up of 31 months (range 0–71). Clinical features and pathological diagnoses (reviewed centrally) were equivalent across both arms. The median age in years (range; number >60 y) for CMD was 56 (32–72; 68) and for FMD 55 (29–75; 68) and 70% in both arms had stage IV FCCL. For CMD versus FMD, the CRR and PRR after course 4 were 18% v 21% and 72% v 68% and after course 8 or at the end of treatment were 44% v 45% and 47% v 47%. The hazard ratios were in favour of CMD, for OS at 1.65 (95%CI 0.97–2.8, p=0.063) and for PFS at 1.61 (95%CI 1.2–2.17; p=0.0018). The numbers of deaths due to lymphoma were equivalent (19 v 21) but there were fewer deaths in the first year (most due to lymphoma in both arms) with CMD (7 v 15; ns). The difference between those who received between 6 and 8 courses in either arm was not significant (152[80%] v 135[71%]). With CMD there were higher rates of grade 3/4 neutropenia (8 v 1) and infections (29 v 20) but these differences were not statistically significant; other toxicities were low grade and equivalent for both arms. Days between cycles (median 28 days in both arms) and dose adherence (96% and 97%) were equivalent; both regimens were well tolerated and relatively easy to deliver. The equivalent dose intensity, toxicities and RRs of the two arms indicate that the statistically significant superior PFS for CMD was not due to undertreatment in the FMD arm. The outcomes for CMD are at least as good as those reported for other combinations of chemotherapy without R and R-CVP.

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.

Retrospective review of concurrent chest radiation and chemotherapy (CRT) in newly diagnosed stage IV non-small cell lung cancer (NSCLC) with oligometastatic disease (OM) treated with stereotactic radiation.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20539-e20539
Author(s):  
Preeti Narayan ◽  
Anamaria R Yeung ◽  
Olushola Ogunlari ◽  
Chris G Morris ◽  
Priya Kadambi Gopalan
Keyword(s):  
Retrospective Review ◽  
Palliative Chemotherapy ◽  
Survival Rates ◽  
Lung Nodule ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Primary Treatment ◽  
Newly Diagnosed ◽  
Stereotactic Radiation ◽  
The Brain

e20539 Background:The primary treatment for patients (pts)with stage IV NSCLC is palliative chemotherapy (CT), with a median OS of approximately 10-12 months, and 5-year survival of ~2%. Several studies have demonstrated that pts with a lung nodule with a solitary brain or adrenal metastasis can achieve relatively high 5-year survival rates with resection of the metastasis and the lung nodule. Studies have also demonstrated that OM can be effectively treated with stereotactic body radiation (SBRT) or stereotactic radiosurgery (SRS) to the brain. We hypothesize that treatment of OM with SBRT and/or SRS and treatment of the thoracic disease with CRT will improve survival over palliative chemotherapy alone. Methods:A retrospective review of charts in the RADTRACS database at the Univ of Florida was conducted between 1/1/2010 - 6/30/2015 to identify pts with newly diagnosed stage IV NSCLC with 5 or less OM at diagnosis that were treated with concurrent CT and definitive RT (60-66 Gy) to the primary lung mass in addition to SRS and/or SBRT to the OM. Date and site of first progression, and date of death/last follow-up were noted. Endpoints included median progression free survival (PFS) and median overall survival (OS). Results:26 pts met these criteria. 20 pts (77%) had recurrence of disease after treatment with CRT + SRS/SBRT. Median PFS was 6 months, and median OS was 14.4 months. Of the 20 recurrences, 10 (50%) were in the brain, while 10 (50%) were in non-CNS sites. One year OS was 60% and 3-year survival was 33% in our patients. When pts with CNS OM at diagnosis were compared to non-CNS OM, PFS (5.5 vs 5.8 months, respectively, p > 0.05) and OS (16.6 vs 13.8 months, respectively, p > 0.05) were similar. 8/12 CNS OM pts progressed in the brain while only 3/9 non-CNS OM progressed in the brain. Of the 5 patients with no progression, 4/5 had non-CNS OM at diagnosis. Conclusions:When compared to standard palliative CT where median OS 10-12 months, median OS was 14.4 months in our pts treated with CRT + SBRT/SRS. This data suggests a possible role for more aggressive treatment of stage IV NSCLC pts with SBRT/SRS to OM and definitive chest CRT.

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.

Sign in / Sign up

Export Citation Format

Share Document