scholarly journals Daratumumab as Single Agent in Relapsed/Refractory Myeloma Patients: A Retrospective Real-Life Survey

2021 ◽  
Vol 11 ◽  
Author(s):  
Uros Markovic ◽  
Alessandra Romano ◽  
Vittorio Del Fabro ◽  
Claudia Bellofiore ◽  
Anna Bulla ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stable Disease ◽  
Partial Remission ◽  
Univariate Analysis ◽  
Single Agent ◽  
Real Life ◽  
Progression Free Survival ◽  
Median Number ◽  
Multicentric Study ◽  
Grade 3

BackgroundThe anti-CD38 monoclonal antibody daratumumab is approved as a single agent for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who received at least three prior lines of therapy, including proteasome inhibitor and immunomodulatory agent. A retrospective multicentric study was designed to evaluate feasibility, tolerability, and efficacy of daratumumab in monotherapy in RRMM.MethodsThis study included 44 consecutive RRMM patients that underwent daratumumab monotherapy after a median number of four prior therapies (range 2–9). Patients were treated in seven Sicilian centers, as part of Sicilian Myeloma Network and three Calabrian centers outside of controlled clinical trials from August 2016 through July 2020.ResultsThe regimen was well tolerated with few grade 3–4 haematological and rare non-haematological adverse events, such as pneumonia. Definitive discontinuation was due to disease progression in 25 (57%) patients. Since three patients did not complete at least one full cycle, a total of 41 patients was evaluated for response. Overall response rate was 37%, and the disease control rate (stable disease or better) was high (73%). The best achieved responses within 6 months were very good partial remission or better (27%), partial remission (10%), minimal response (14%) and stable disease (22%). After a median follow up of 7.8 months, median progression free survival (PFS) was 7.2 months and overall survival (OS) 7.8 months. Univariate analysis showed that patients with PR or better after 6 months of therapy had longer median PFS and OS (respectively 29.5 vs 3.6 months, p=0.0001 and 30.6 vs 3.9 months p=0.0001), confirmed by multivariate analysis. Furthermore, standard cytogenetic risk and biochemical relapse type had prolonged median PFS, but not OS (respectively unreached vs 2.6, p=0.03 and 23.9 vs 6.2, p=0.05) in both univariate and multivariate analysis. Additionally, univariate analysis showed that patients treated with carfilzomib-lenalidomide-dexamethasone prior to daratumumab had significantly shorter PFS compared to pomalidomide-dexamethasone (3.4 months vs 9.3 months, p=0.03), that multivariate analysis failed to confirm.ConclusionsOur findings indicate that daratumumab as single agent is safe and well-tolerated regimen in real-life, associated to prolonged PFS and OS in responding patients. No new safety signals were identified.

scholarly journals Clinical Benefit of Long-Term Disease Control with Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients

2019 ◽  
Vol 8 (10) ◽  
pp. 1695 ◽  
Author(s):  
Marina Silvia Parisi ◽  
Salvatore Leotta ◽  
Alessandra Romano ◽  
Vittorio Del Fabro ◽  
Enrica Antonia Martino ◽  
...  
Keyword(s):  
Disease Control ◽  
Stable Disease ◽  
Partial Remission ◽  
Univariate Analysis ◽  
Real Life ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Median Number ◽  
Response To Treatment ◽  
Depth Of Response

Background: We retrospectively analysed relapsed/refractory MM (RRMM) patients treated with pomalidomide and dexamethasone (PomaD) either in real life, or previously enrolled in an interventional (STRATUS, MM-010) or currently enrolled in an observational study (MM-015) to provide further insights on safety and tolerability and clinical efficacy. Methods: Between July 2013 and July 2018, 76 RRMM patients (including 33 double refractory MM) received pomalidomide 4 mg daily given orally on days 1–21 of each 28-day cycle, and dexamethasone 40 mg weekly (≤75 years) or 20 mg weekly for patients aged > 75 years. In nine patients a third agent was added to increase the response: Cyclophosphamide (in two fit patients) or clarithromycin (in seven frail patients). Patients received subcutaneous filgrastim as part of the prophylaxis regimen for neutropenia. Results: A median number of six (range 2–21) PomaD cycles were given. The regimen was well tolerated with grade 3–4 haematological and non-haematological adverse events in 39 (51%) and 25 (33%) patients, respectively. In patients who developed serious AE, pomalidomide dose reduction (11%, 14%) or definitive discontinuation (18%, 23%) were applied. All patients have been evaluated for response within the first two cycles. The disease control rate (DCR), i.e., those patients that had a response equal or better than stable disease (≥ SD), was high (89%), with 44% overall response rate (ORR) after six cycles. The achieved best responses were complete remission (CR, 5%), very good partial remission (VGPR, 4%), partial remission (PR, 35%), minimal response (MR, 7%), and stable disease (SD, 38%). After a median follow up of 19.6 months, median progression free survival was 9.4 months, and overall survival (OS) was 19.02 months. Univariate analysis showed that double refractory patients, or who received more than three previous lines had shorter PFS. At 18 months, regardless of the depth of response, patients with a disease control of at least six months, defined as maintenance of a best clinical and/or biochemical response to treatment for almost six months, had prolonged PFS (35.3% versus 20.6%, p = 0.0003) and OS (81.2% versus 15.9%, p < 0.0001) Conclusions: Our findings indicate that PomaD is a safe and well-tolerated regimen in real-life, associated with prolonged PFS and OS with acceptable toxicity. Moreover, Pd induced disease control in most intensively pre-treated patients and some of them achieved longer PFS than that obtained with the previous treatment.

Bortezomib and Dexamethasone as Maintenance therapy in Relapse/Refractory multiple myeloma Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2771-2771 ◽  
Author(s):  
Giulia Benevolo ◽  
Alessandra Larocca ◽  
Patrizia Pregno ◽  
Francesca Gay ◽  
Barbara Botto ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Median Time ◽  
Salvage Therapy ◽  
Univariate Analysis ◽  
Single Agent ◽  
Haemoglobin Concentration ◽  
Progression Free Survival ◽  
Median Number

Abstract Background: Despite the advances in the treatment for multiple myeloma (MM) in the past decade, it still remains an incurable haematological disease and the majority of patients still experience relapse. Bortezomib is a novel proteasome inhibitor approved for the treatment of MM patients. Several studies have demonstrated its efficacy as front-line therapy and in relapsed, advanced MM but no data are available as maintenance therapy (MT) in refractory/relapsed MM. Patients and methods: The aim of this study is to evaluate the safety and the efficacy of bortezomib/dexamethasone MT (1.3 mg/mq bortezomib on days 1 and 15; 20 mg dexamethasone on days 1–2 and 15–16 in a 28-day cycle for a total of 6 cycles) in patients with refractory/relapse MM who responded to salvage therapy. Results: From October 2004 until April 2008, 40 MM patients have been enrolled. The characteristics of the patients were as follows: 20 males and 20 females, median age was 70 years (IQR:66–75). Median haemoglobin value was 10.85 (IQR:10.175–12.225) and 7 (18%) patients had a renal failure. Skeletal disease was present in 27 (68%) patients. The median number of prior therapies was 2 (1–4). The salvage therapy included bortezomib as single agent or in combination with steroids and/or thalidomide in 12 patients (30%). Median time from diagnosis to the first dose of MT was 41 months (IQR:26–59). The median number of bortezomib infusion was 8 (1–18). After a median follow up of 13 months (IQR:6–31), 10 patients died for PD and 4 patients for infections. The MT improved the quality of response and converted in 1 CR and 4 VGPR the PR after salvage therapy in 5 patients; moreover, we observed a remarkable decreased of M component in 11 patients. The median time to progression was 23 months (95%CI: 8-not reached) with a progression free-survival at 1 year of 69% (95%CI: 50–82). The overall survival at 1 years was 63% and the cumulative incidence of death due to PD adjusted for competitive risk event was 25% (95%IC:10–41). In a univariate analysis the response rate to MT was not significantly affected by age, sex, number or type of previous therapy and haemoglobin concentration. Non-dose-limiting toxicities included neuropathy grade 1 (12 pts), herpes zoster reactivation (2 pts) and gastrointestinal affections (1 pts). Conclusion: The combination bortezomib/dexamethasone can be safely administered as a maintenance therapy in relapse/refractoy MM. These preliminary data suggest that bortezomib/dexametasone MT can improve remission duration and also quality of response with an acceptable toxicity.

Irinotecan monotherapy as second-line treatment in advanced pancreatic cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15111-15111 ◽  
Author(s):  
Y. Park ◽  
S. Yi ◽  
H. Kim ◽  
S. Lee ◽  
I. Hwang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stable Disease ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Median Number ◽  
Line Treatment ◽  
Second Line ◽  
Best Response ◽  
Grade 3 ◽  
Number Of Cycles

15111 Background: The aim of this phase II study was to determine whether second line therapy with single agent irinotecan could provide any clinical benefit in patients with gemcitabine- pretreated advanced pancreatic cancer. Methods: From January 2004 to October 2006, patients with advanced pancreatic cancer previously treated with gemcitabine alone or combination were treated with single agent irinotecan(150 mg/m2, biweekly), until unacceptable toxicity or disease progression. Primary endpoint was response rate with single stage design. Results: Twenty-eight patients were enrolled(22 male, 6 female, median age : 54.5 years (39–76)). Nine patients are still alive and 3 remain on therapy with stable disease. The median number of cycles was 3.5(1–12). Twenty-four patients were assessable for toxicity and 21 for response. The most common toxicities was diarrhea (grade 3, 12.5%). Grade 3 neutropenia in 1 patient was observed. Other hematological and non-hematological toxicities were mild and manageable. Partial responses were observed in 3 patients (3/21, 14%). An additional 9 patients (9/21, 43%) had stable disease as their best response. 12 patients have progressed with a median time-to-progression of 4.0 months. Conclusions: Single-agent irinotecan was tolerated with manageable toxicity, offering encouraging activity as second-line treatment of patients with advanced pancreatic cancer, refractory to gemcitabine. No significant financial relationships to disclose.

A phase II study of picoplatin (pico) as second-line therapy for patients (pts) with small cell lung cancer (SCLC) who have resistant or refractory disease or have relapsed within 180 days of completing first-line, platinum (plat)-containing chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7722-7722 ◽  
Author(s):  
D. Bentzion ◽  
O. Lipatov ◽  
I. Polyakov ◽  
R. MacKintosh ◽  
J. Eckardt ◽  
...  
Keyword(s):  
Median Survival ◽  
Stable Disease ◽  
Single Agent ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Refractory Disease ◽  
Phase 2 ◽  
First Line ◽  
Line Therapy ◽  
Grade 3

7722 Background: Pico is a sterically hindered plat analogue designed to overcome plat resistance with improved safety and efficacy. In >600 pts pico had single-agent activity in lung, prostate, ovarian and other malignancies with rare significant nephro-, oto-, or neurotoxicity (∼2% grade 3 and 0% grade 4). In a previous phase 2 study of single agent pico as 2nd line therapy in SCLC, 4 of 48 pts (8%) had a partial response and 21 (44%) stable disease. Median survival was 27.0 (95% CI = 16–35) wks. This multi-center phase 2 trial was designed to confirm the activity of pico as 2nd line monotherapy for plat-resistant SCLC. Methods: Pts with SCLC who either 1) failed or progressed through 1st line plat-containing chemo (refractory disease), or 2) initially responded to 1st line plat-containing chemo and then relapsed/ progressed within 3 months (resistant disease), or 3) initially responded and then relapsed/progressed between 90 to 180 days (sensitive, relapsed 90 to 180 days), had measurable disease and ECOG PS 0–2 were treated with pico, 150 mg/m2 iv over1–2 hrs, q 21 days. Tumor response was assessed q 6 wks. Adverse events (AEs) were graded using the NCI CTCAE. Results: 77 pts received pico (45 refractory, 27 resistant, 5 sensitive). The median number of cycles received was 2 (mean = 2.9). The most frequently reported AEs of any severity were thrombocytopenia (39% of pts), anemia (35%), neutropenia (22%), nausea (20%), emesis (14%) and dyspnea (25%). Neutropenic fever occurred in 1 pt; there were no treatment related deaths. One pt had grade 3 neuropathy; there was no grade 3 or 4 ototoxicity or nephrotoxicity. Median overall survival is 28.1 (95% CI = 26–37) wks. Median progression free survival is 9.3 (95% CI = 7–12) wks. Of 63 pts with at least 1 post-treatment assessment of disease status, 33 (52%) had stable disease. Conclusion: Median survival compares favorably with other therapeutic options and toxicity is reduced in pico treated SCLC pts who have failed prior plat-containing first-line chemo or who have progressed within 180 days of first-line chemo. A phase III trial to confirm these results has been initiated. No significant financial relationships to disclose.

Efficacy and safety of amrubicin in patients with advanced or recurrent thymoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17513-e17513
Author(s):  
Kiyotaka Yoh ◽  
Koichi Goto ◽  
Seiji Niho ◽  
Shigeki Umemura ◽  
Hironobu Ohmatsu ◽  
...  
Keyword(s):  
Tumor Size ◽  
Single Agent ◽  
Reduction Rate ◽  
Progression Free Survival ◽  
Median Number ◽  
Significant Activity ◽  
Efficacy And Safety ◽  
Kaplan Meier ◽  
Grade 3 ◽  
Number Of Treatment

e17513 Background: Thymoma is rare thoracic tumor, which is chemoresponsive with anthracycline or cisplatin-containing regimen in advanced or recurrent setting. Amrubicin is a novel anthracycline agent that is well known to exert significant activity against small-cell lung cancer. The purpose of this study was to determine the efficacy and safety of amrubicin in patients with advanced or recurrent thymoma. Methods: We reviewed 11 consecutive patients with advanced or recurrent thymoma treated with single-agent amrubicin therapy at our institution from May 2006 to September 2010, retrospectively. Amrubicin was administered intravenously at 40 or 45 mg/m2 on day 1 to 3 of 3-4 weeks until disease progression or development of intolerance. Results: Profile of patients included: median age was 57 years (range 25–74); Male/Female=5/6; PS 0/1= 7/4; and Masaoka stage IVA/IVB/recurrence=7/2/2. All patients had received no prior chemotherapy. The median number of treatment cycles was 4 (range 3-6). A partial response was achieved in 1 patient and 10 patients exhibited stable disease. The overall response rate was 9%, but 3 patients had at least a 20% reduction in tumor size with amrubicin. The median reduction rate in tumor size was 13% (range 0-40). The median progression-free survival period was 5.4 months (range 2.3-15.8 months). The median overall survival has not been reached although a median follow-up time was 2.5 years. Based on the Kaplan-Meier method, the estimated 3-year survival rate was 83%. The most common adverse events were hematological toxicities. Five patients had grade 3/4 neutropenia, but febrile neutropenia was not observed. Non-hematological grade 3 toxicities were less frequent. There were no treatment-related deaths. Conclusions: Single-agent amrubicin showed modest activity and acceptable safety profile as chemotherapy for advanced or recurrent thymoma. Additional testing of amrubicin combined with cisplatin in this disease is warranted.

A large multicentric study of gemcitabine-based regimen in relapsed or refractory Hodgkin lymphoma (HL) patients (pts)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18518-18518
Author(s):  
P. Validire ◽  
C. Fermé ◽  
P. Brice ◽  
M. Diviné ◽  
J. Gabarre ◽  
...  
Keyword(s):  
Initial Dose ◽  
Soft Tissues ◽  
Univariate Analysis ◽  
Single Agent ◽  
Complete Response ◽  
Median Number ◽  
Multicentric Study ◽  
Chemotherapeutic Regimen ◽  
Heavily Pretreated ◽  
One Year

18518 Background: The aim of this study was to assess the efficacy and safety of gemcitabine-based regimen in heavily pretreated HL pts. Methods: Relapsed or refractory HL pts treated with gemcitabine were retrospectively reviewed. Gemcitabine was used as a single agent or administered in combination with vinorelbine, oxaliplatine, doxorubicine, vinblastine, rituximab, and/or corticosteroids. Results: Fifty-five pts treated in 9 departments of clinical hematology between January 1999 and August 2006 were included in the study. Initial characteristics before gemcitabine administration were: nodular sclerosis in 84%; sex ratio M/F 1.1; median age 29 years (range: 15–85 years); advanced stage 84%; extranodal sites were lung, bone, liver, soft tissues, and bone marrow in 68%, 31%, 13%, 21%, and 4%, respectively; Hasenclever index lower than 3 in 20/43 cases (47%). At the end of the first front-line therapy (chemotherapy ± radiotherapy), 19 pts (35%) were in complete response (CR) in whom 13 relapsed within one year, 5 were in partial response (PR), and 31 pts were primary refractory (56%). Median number of previous chemotherapeutic regimen was 3 (range 1–8), 39 pts (71%) have received radiotherapy (RT), and 34 pts (62%) one or two autologous/allogenic stem cell transplantations (A/ASCT). Twenty-nine pts received gemcitabine alone with a median initial dose per injection of 750 mg/m2 (range: 180–1250 mg/m2); Gemcitabine was administered at an initial dose per injection of 1000 mg/m2 (range: 500–1250) in combination with vinorelbine in 10 pts, oxaliplatine in 13 pts in whom 4 with rituximab, and with others drugs in 3 pts. In both cases, the median number of combined gemcitabine regimen injections was 6 (range: 1–27). Toxicity was mainly hematological (75% of pts developed bi- or pancytopenia) or infectious (13%). Among all included pts, 6 were in CR (11%) and 5 in PR with an overall response rate of 20%. Among the 6 CR, 5 pts received thereafter A/ASCT and 2 pts RT, with 2 persistent CR at 16 and 44 months. In univariate analysis, none prognostic factor for response to gemcitabine was identified. Conclusions: This study, which constitutes one of the most important series, showed a mild efficacy of gemcitabine-based regimen in heavily pretreated HL patients. No significant financial relationships to disclose.

Phase II trial of sorafenib in esophageal (E) and gastroesophageal junction (GEJ) cancer: Response observed in adenocarcinoma.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 41-41 ◽  
Author(s):  
D. Ilson ◽  
Y. Y. Janjigian ◽  
M. A. Shah ◽  
L. H. Tang ◽  
D. P. Kelsen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stable Disease ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Gastroesophageal Junction ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Node Disease ◽  
Grade 3

41 Background: Sorafenib is a tyrosine kinase inhibitor targeting VEGFr, PDGFr, Raf and other pathways. Encouraging response and survival were observed in a phase II trial combining sorafenib with chemotherapy in GE cancer (J Clin Oncol 27:2947;2010). We are studying single agent sorafenib in a phase II trial with the primary endpoint to assess progression free survival (PFS). Secondary endpoints include response and therapy tolerance. Methods: Patients (pts) with measurable metastatic E and GEJ cancer with no more than 3 prior chemotherapy regimens were treated with sorafenib 400 mg BID. CT scans were performed monthly for the first 2 months, then every 2 months. Results: Sixteen of 35 pts have been accrued and 14 are currently evaluable. 13 male, 3 female, median KPS 80%, age 58, GEJ 7, E 9, squamous 2, adenocarcinoma (AC)14. An ongoing complete response (11+ months) was observed in a pt with biopsy proven metastatic neck lymphadenopathy (E primary AC, recurrence after prior chemoradiotherapy and surgery). A second pt (GEJ AC) had protracted stable disease in bulky celiac node disease (15+ months). Grade 3 toxicity was limited to skin rash (1 pt), hand foot reaction (1 pt), and fatigue (1 pt). Only 3 of 14 pts (21%) had early disease progression at 2 months or less. Median PFS 4 mos, 4 patients (29%) continue on therapy for more than 7 months. The majority of tumors tested positive for phospho-erk by immunohistochemistry (11/14, 79%). Conclusions: The observation of a durable complete response and protracted stable disease to sorafenib in E cancer is remarkable. Further accrual continues to define PFS. Supported by a grant from Bayer. [Table: see text]

Bendamustine + Rituximab (BR) Chemoimmunotherapy and Maintenance Lenalidomide in Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL): A Wisconsin Oncology Network (WON) Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3647-3647
Author(s):  
Julie E. Chang ◽  
Chong Zhang ◽  
KyungMann Kim ◽  
Rachel Kirby ◽  
Lynn Volk ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Stable Disease ◽  
Research Funding ◽  
Progressive Disease ◽  
Single Agent ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Fish Analysis ◽  
Minor Response ◽  
Grade 3

Abstract Abstract 3647 Introduction: BR chemoimmunotherapy was shown to have an overall response rate (ORR) of 59%, a median progression-free survival (PFS) of 14.7 months, and an acceptable toxicity profile in R/R CLL (Fischer K, et al. J Clin Oncol 2011). Given the single-agent activity of lenalidomide in R/R CLL/SLL, we hypothesized that maintenance lenalidomide after BR induction could improve PFS. Methods: Thirty-four patients requiring therapy for R/R CLL/SLL were treated with bendamustine 90 mg/m2 IV on days 1 & 2 and rituximab 375 mg/m2 IV on day 1 every 28 days for a maximum of 6 cycles. Growth factor support was permitted. Patients achieving at least a minor response (objective improvement even if not meeting criteria for partial response) were eligible to proceed with 12 cycles of maintenance therapy with lenalidomide 5–10 mg/day orally given continuously in each 28-day cycle. Patients were eligible if they had histologically proven CLL/SLL and had received >1 but ≤5 prior cytotoxic chemotherapy regimens (retreatment with an identical regimen was not counted as a separate treatment). The primary endpoint was PFS. Results: Baseline characteristics include median age 67 (range 38–86), 25 men/9 women, 26 CLL/8 SLL, and median of 2 prior therapies (range 1–4). Cytogenetic profiling by FISH analysis was available in 22 patients (65%), with 11/22 demonstrating presence of 17p and/or 11q deletions. Twenty-five patients (74%) completed 6 cycles of induction BR. Two patients died from toxicities of pneumonia and heart failure during cycle 1; 7 patients received <6 cycles due to toxicities (n=4), progressive disease (n=2), and stable disease (n=1). Dose modifications were required in 14 (41%) patients, most commonly for neutropenia (12/14), thrombocytopenia (3/14), and weight loss/failure to thrive (3/14). Grade 3/4 toxicities were primarily hematologic, with neutropenia in 20 patients, anemia in 1, and thrombocytopenia in 7. Febrile neutropenia occurred in 4 patients. Infections with or without neutropenia were common; grade 2 infections in 16 patients, grade 3 in 7 patients. Grade 2 rash occurred in 4 patients. Eleven deaths have been observed, 7 events due to progressive disease (including 2 events of transformed lymphoma). Responses were evaluable in 31/34 patients. The ORR was 65%, with 6 complete (18%) and 16 partial (47%) responses. An additional 7 patients achieving stable disease were eligible to proceed to maintenance therapy. With a median follow up of 20.1 months, the median PFS and overall survival are 24.3 months and 27.9 months, respectively. Conclusions: In our multicenter trial for patients with R/R CLL/SLL, the BR induction produced an ORR that is comparable to historical observations (65% vs 59%). However, the median PFS is longer (24.3 vs 14.7 months), suggesting maintenance lenalidomide may be contributing to an improved response duration. Based upon these promising results, we have initiated a successor study in which patients will receive lenalidomide plus rituximab maintenance after a BR induction. Disclosures: Chang: Celgene: Research Funding; Genentech: Research Funding. Off Label Use: Lenalidomide as maintenance therapy for CLL after induction rituximab + bendamustine chemoimmunotherapy. Fenske:Spectrum Pharmaceuticals: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Kahl:Millennium: Consultancy, Research Funding; Roche: Consultancy; Genentech: Consultancy, Research Funding.

Phase II trial of irinotecan plus bevacizumab for heavily pretreated recurrent ovarian cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5016-5016
Author(s):  
Salvia Sanjay Jain ◽  
Yan G. Makeyev ◽  
Franco Muggia ◽  
James L. Speyer ◽  
John Patrick Curtin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Single Agent ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Median Number ◽  
Protocol Amendment ◽  
Platinum Sensitive ◽  
Duration Of Response ◽  
Heavily Pretreated ◽  
Grade 3

5016 Background: Irinotecan and bevacizumab have single agent activity in platinum sensitive (PSen) and resistant (PRes) ovarian cancer patients (pts). We sought to evaluate the efficacy and toxicity of irinotecan plus bevacizumab in these pts. The trial was designed to evaluate whether the progression free survival (PFS) at 6 months is at least 40% and with secondary objectives of estimating response rate (RR), duration of response (DoR), time to progression and toxicity. Methods: No limitation on number of prior regimens was placed, and prior use of study drugs was allowed. Irinotecan 250mg/m2 and bevacizumab 15mg/kg every 3 weeks were given. Due to treatment-related grade 3 toxicity (diarrhea and neutropenia) experienced by the first 5 pts on the study, the dose of irinotecan was amended to 175mg/m2. Results: 20 pts with recurrent ovarian cancer [PSen 5, PRes 15] of a planned 35 have been recruited thus far. Median age is 59 (45-78). Median number of prior regimens is 5 (3-12) with 9 pts demonstrating progressive disease (PD) on prior topotecan-containing regimens and 7 pts exhibiting PD on prior bevacizumab-containing regimens. 4 pts discontinued treatment before 2 cycles (2 for protocol defined toxicity, 2 by patient/physician choice). Partial response (PR) was observed in 2 PSen pts and 1 PRes pt, while stable disease (SD)was seen in 9 (2 PSen, 7 PRes) out of the 15 pts assessable for response at this time. 3 pts demonstrated PD after 2 cycles of treatment. 12 of 13 pts with PR or SD by RECIST also had response by CA125 criteria. Median DoR thus far (SD plus PR) is 18 weeks (4-37). 6 pts have ongoing response (4-18 weeks). Of 19 pts that received > 2 cycles, 3 had grade 3 diarrhea (2 before protocol amendment and 1 after). 2 pts had grade 3/4 neutropenia (1 before and 1 after protocol amendment). Median PFS is 9.6 months (mts). Median overall survival is 15.5 mts. PFS rate at 6 mts is 61% with 95% confidence interval: (40%, 92%). Conclusions: Results of the trial to date suggest the hypothesis that the PFS at 6 mts is less than 40% can be rejected. Activity of this regimen is encouraging given the heavily pretreated nature of the pts. Dose-limiting diarrhea and neutropenia required protocol amendment. We continue to accrue study subjects at the amended dosing.

Phase II trial of sorafenib in esophageal (E) and gastroesophageal junction (GEJ) cancer: Response and prolonged stable disease observed in adenocarcinoma.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 91-91
Author(s):  
Geoffrey Y. Ku ◽  
Yelena Yuriy Janjigian ◽  
Manish A. Shah ◽  
Jessica Herrera ◽  
Laura H. Tang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stable Disease ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Gastroesophageal Junction ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Secondary Endpoints ◽  
Grade 3

91 Background: Sorafenib is a tyrosine kinase inhibitor targeting VEGFr, PDGFr, Raf and other pathways. Encouraging response and survival were observed in a phase II trial of sorafenib with chemotherapy in GE cancer (J Clin Oncol 27:2947;2010). We performed a phase II trial of single-agent sorafenib with the primary endpoint of progression-free survival (PFS). Secondary endpoints include response and toxicity. Methods: Patients (Pts) with measurable metastatic E and GEJ cancer with ≤3 prior chemotherapy regimens were treated with sorafenib 400 mg BID. CT scans were performed monthly for the first 2 months, then every 2 months. Results: Thirty-five patients have been accrued, with 34 evaluable; median age 62, 31 male, 4 female, median KPS 80%, E 25, GEJ 10, adenocarcinoma (AC) 30 squamous 5, median no. of prior therapies 2. Of 31 response-evaluable Pts, 1 (3%) ongoing complete response was noted (34+ months) in a Pt with E AC with biopsy-proven lymph node recurrence after chemoradiation and surgery; 23 Pts (74%) had stable disease. Median PFS is 3.7 months (95% CI 1.9 to 4 months), with median overall survival 8.9 months (95% CI 6.9 to 11.6 months). Four patients remain on treatment. Significant grade 3 toxicities included hand foot reaction (3 Pts), rash (1 Pt), dehydration (3 Pts) and fatigue (2 Pts). Twenty-seven of 33 tumors (82%) tested positive for phospho-ERK by immunohistochemistry. Conclusions: Encouraging activity in terms of PFS has been noted in this heavily pre-treated population. Updated data will be presented. Supported by a grant from Bayer. Clinical trial information: NCT00917462.

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