scholarly journals Safety and activity of pembrolizumab in combination with rituximab in relapsed or refractory follicular lymphoma

2022 ◽  
Author(s):  
Loretta J. Nastoupil ◽  
Collin K Chin ◽  
Jason R Westin ◽  
Nathan H Fowler ◽  
Felipe Samaniego ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Follicular Lymphoma ◽  
Liver Enzyme ◽  
Response Rate ◽  
Progression Free Survival ◽  
Complete Response ◽  
Low Grade ◽  
Phase 2 ◽  
Open Label ◽  
Grade 3

PD-1 blockade enhances the function of anti-tumor T-cells and antibody-dependent cell-mediated cytotoxicity (ADCC) of NK cells. In a single-center, open-label, phase 2 trial, we tested the combination of pembrolizumab, an anti-PD-1 monoclonal antibody and rituximab, an anti-CD20 monoclonal antibody that induces ADCC, in 30 follicular lymphoma (FL) patients with rituximab-sensitive disease who relapsed after ≥1 prior therapy. Pembrolizumab was administered at 200mg IV every 3 weeks for up to 16 cycles and rituximab was given at 375mg/m2 IV weekly for 4 weeks in cycle 1 only. The most common grade 3/4 adverse events (AE) were liver enzyme abnormalities (3%), diarrhea (3%), nausea (3%), aseptic meningitis (3%) and pancreatitis (3%). Low-grade immune-related AEs were reported for 80% of patients, including diarrhea (43%), liver enzyme abnormalities (33%), thyroid dysfunction (27%), and rash (23%). Grade 3 or 4 immune related AEs occurred in 13% of patients. Treatment-related AEs led to discontinuation in 6 (20%) patients. Overall response rate (primary endpoint) was 67% and complete response rate was 50%. Median progression-free survival (PFS) was 12.6 months (95% CI, 8.2-27.6 months), the 3-year overall survival rate was 97%, and 23% of patients were in remission at a median follow up of 35 months. Presence of a high CD8+ T-effector score at baseline in the tumor was associated with induction of a complete response and improved PFS. In this single arm, phase 2 study, the combination of pembrolizumab and rituximab demonstrates favorable efficacy and safety profile in relapsed FL. This trial is registered at www.clinicaltrials.gov: NCT02446457.

Rituximab in Combination With Fludarabine Chemotherapy in Low-Grade or Follicular Lymphoma

2005 ◽  
Vol 23 (4) ◽  
pp. 694-704 ◽  
Author(s):  
M.S. Czuczman ◽  
A. Koryzna ◽  
A. Mohr ◽  
C. Stewart ◽  
K. Donohue ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Response Rate ◽  
Complete Response Rate ◽  
Complete Response ◽  
Infectious Complications ◽  
Hematologic Toxicity ◽  
Low Grade ◽  
Similar Response ◽  
Open Label ◽  
Treatment Naïve

Purpose To evaluate the safety and efficacy of fludarabine plus rituximab in treatment-naïve or relapsed patients with low-grade and/or follicular non-Hodgkin's lymphoma. Patients and Methods This was an open-label, single-arm, single-center phase II study enrolling 40 patients. During the first week of the study, patients received two infusions of rituximab 375 mg/m2 administered 4 days apart. Seventy-two hours after the second infusion of rituximab, patients received the first of six cycles of fludarabine chemotherapy (25 mg/m2/d for 5 days on a 28-day cycle). Single infusions of rituximab were administered 72 hours before the second, fourth, and sixth cycles of fludarabine, and two infusions of rituximab were given 4 weeks after the last cycle of fludarabine. Treatment duration was 26 weeks. Results An overall response rate of 90% (80% complete response rate) was achieved in the intent-to-treat population. Similar response rates were seen in treatment-naïve and previously treated patients. The median duration of response has not been reached at 40+ months. The median follow-up time in this study is 44 months (range, 15 to 66 months). In patients positive for the 14;18 translocation in blood and/or marrow at enrollment, molecular remission was achieved in 88% of cases, with patients remaining negative for up to 4 years to date. Hematologic toxicity was manageable, and except for a 15% incidence of herpes simplex/zoster infections, infectious complications were rare. Nonhematologic toxicities were minimal. Conclusion Rituximab plus fludarabine was well tolerated and associated with an excellent complete response rate, including molecular remissions, in patients with low-grade or follicular lymphoma.

Bortezomib, Bendamustine, and Rituximab in Patients With Relapsed or Refractory Follicular Lymphoma: The Phase II VERTICAL Study

2011 ◽  
Vol 29 (25) ◽  
pp. 3389-3395 ◽  
Author(s):  
Nathan Fowler ◽  
Brad S. Kahl ◽  
Peter Lee ◽  
Jeffrey V. Matous ◽  
Amanda F. Cashen ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Response Rate ◽  
International Workshop ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Free Survival ◽  
Highly Active ◽  
Grade 3

Purpose The aims of this multicenter study were to evaluate the response rate, progression-free survival, and toxicity of the combination of bortezomib, bendamustine, and rituximab in patients with follicular lymphoma whose disease was relapsed or refractory to prior treatment. Patients and Methods Patients received five 35-day cycles of bortezomib, bendamustine, and rituximab: bortezomib administered intravenously (IV) at a dose of 1.6 mg/m2 on days 1, 8, 15, and 22, cycles one to five; bendamustine 50, 70, or 90 mg/m2 IV over a 60-minute infusion on days 1 and 2, cycles one to five; and rituximab 375 mg/m2 on days 1, 8, 15, and 22 of cycle one and day 1 of subsequent cycles. Patients were assessed using the International Workshop Response Criteria, with the primary end point of 60% complete response rate. Results Seventy-three patients were enrolled. During the dose-escalation phase, the maximum-tolerated dose for bendamustine was not reached; the 90 mg/m2 dose level was expanded for the efficacy assessment, and a total of 63 patients received bendamustine 90 mg/m2. In these 63 patients, the overall response rate was 88% (including 53% complete response). Median duration of response was 11.7 months (95% CI, 9.2 to 13.3). Median progression-free survival was 14.9 months (95% CI, 11.1 to 23.7). Toxicities were manageable; myelosuppression was the main toxicity (25% and 14% of patients experienced grade 3 to 4 neutropenia and grade 3 to 4 thrombocytopenia, respectively). Transient grade 3 to 4 neuropathy occurred in 11% of patients. Conclusion The combination of bortezomib, bendamustine, and rituximab is highly active in patients with follicular lymphoma who have received previous treatment.

Immune priming with nivolumab followed by nivolumab and rituximab in first-line treatment of follicular lymphoma: The phase 2 1st FLOR study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7560-7560
Author(s):  
Eliza Anne Hawkes ◽  
Sze Ting Lee ◽  
Geoff Chong ◽  
Michael Gilbertson ◽  
Andrew Grigg ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Response Rate ◽  
Nk Cell ◽  
Single Agent ◽  
Stage Iv ◽  
Complete Response ◽  
Phase 2 ◽  
Open Label ◽  
Immune Priming ◽  
Biomarker Analysis

7560 Background: Standard of care immunochemotherapy in front-line (1L) follicular lymphoma (FL) is highly efficacious but not without significant toxicity. High rates of grade 3-5 adverse events (AEs), primarily infection and bone marrow suppression, are experienced in up to 75% of patients. A more tolerable but equally effective approach is required. PD-1 inhibition, in combination with rituximab (R), increases T cell anti-tumour effect & enhances NK cell antibody dependent cell cytotoxicity, with proven efficacy in relapsed FL. The concept of ‘priming’ the immune system with nivolumab (N) prior to tumour-directed therapy has rationale and evidence, but the safety of this approach in 1L FL is not described. Methods: ‘1st FLOR’ (NCT03245021) is an open-label, multi-centre, phase 2, Simon’s 2-stage study of N + R (N = 39). Key eligibility were stage III-IV grade 1-3A FL requiring 1L systemic therapy; ECOG ≤2; adequate organ function. All patients (pts) receive induction N 240mg IV 2-weekly for 4 cycles. Pts with complete response (CR) receive 4 further cycles of 240mg IV N monotherapy then 12 cycles of maintenance N 480mg IV 4-weekly. Pts with < CR had 240mg N plus 375mg/m2 IV R 2-weekly for 4 cycles followed by maintenance N+R (N 480mg 4 weekly for 12 cycles; R 12 weekly for 8 cycles). Primary endpoint (EP) was ≥ G3 toxicity rate during induction. Secondary EPs; response rate by Lugano response criteria, overall toxicity, PFS, OS. Results: Between September 2017 to March 2020, 39 pts were enrolled. Baseline characteristics included median age of 54 (range: 28-79). stage IV disease in 67%, B Symptoms & bulk (≥7cm) in 23% each, intermediate-high risk FLIPI in 74%. The primary EP was met, with only 16 pts (41%) having ≥G3 toxicity at end of induction. Non-immune AEs were predominantly G1-2; most commonly infection (67%) & fatigue (64%). G3-4 Immune-related AEs were infrequent and included pancreatitis plus hepatitis (N = 1), pancreatitis alone (N = 1), rash (N = 1), transaminitis (N = 2), hypocortisolism (N = 1), hyperglycaemia (N = 3) and asymptomatic lipase/amylase increase (N = 3). Median follow-up was 17.5 months (range: 7-39). Overall response rate was 92% (36/39) with CR in 54% (21/39). Median time to CR was 5 months (m) (range: 2-25). Nine pts (23%) discontinued treatment; 7 due to progressive disease (1 pt died of transformed FL), 2 developed constitutional symptoms (1 stable disease, 1 partial response). In 25 evaluable pts, 12m PFS & OS is 72% (CI 51-88) & 96% (CI 80-100). Biomarker analysis is in progress. Conclusions: Immune-priming with single-agent N, then combination N+R in 1L FL is associated with favourable toxicity and high ORR & CR rates potentially providing an alternative to chemotherapy. Acknowledgements: Bristol-myers Squibb provided funding and nivolumab for this study. Clinical trial information: NCT03245021.

Obinutuzumab short-duration infusion (SDI) in previously untreated advanced follicular lymphoma: Results from the end of induction analysis of the phase IV GAZELLE study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7545-7545
Author(s):  
Miguel Angel A. Canales Albendea ◽  
Thomas A. Buchholz ◽  
Koji Izutsu ◽  
Takayuki Ishikawa ◽  
Laura Maria Fogliatto ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Complete Response ◽  
Primary Analysis ◽  
Open Label ◽  
Secondary Endpoints ◽  
To Receive ◽  
Phase Iv

7545 Background: Obinutuzumab (G)-chemotherapy (chemo) has demonstrated improved progression-free survival compared with rituximab (R)-chemo in previously untreated advanced follicular lymphoma (FL). G is currently administered by IV infusion over ̃3–4 hours. A shorter duration of infusion in Cycle (C) 2 and subsequent cycles, as is standard practice with R, could improve convenience for patients (pts) and efficiency for infusion facilities. We report the primary analysis of the prospective, open-label, multicenter, single-arm, Phase IV, GAZELLE study (NCT03817853), which evaluated the safety of G administered as a 90-minute (min) SDI from C2 onwards in pts with FL. Methods: Pts with previously untreated FL received G (1000mg) intravenously on Day (D) 1, 8, and 15 of C1, and on D1 thereafter, plus chemo (bendamustine, CHOP, or CVP) for 6–8 cycles. In C1, pts received G at the standard infusion rate. Pts without a Grade (Gr) ≥3 infusion-related reaction (IRR) in C1 were eligible to receive G as a 90-min SDI from C2. Pts with a Gr 3 IRR in C1 received the standard G infusion in C2, and were eligible for G SDI in subsequent cycles if no Gr ≥3 IRRs occurred. Pts with a second Gr 3/4 IRR discontinued G. At the end of induction (EOI), responding pts received maintenance G (1000mg) as SDI for 2 years or until disease progression (PD). The primary endpoint was incidence of Gr ≥3 IRRs during C2. IRRs were defined as any event occurring ≤24 hours from infusion judged to be related to treatment. Secondary endpoints included adverse events (AEs) and investigator-assessed overall response rate at EOI. Results: As of December 3, 2020, 113 pts had received study treatment. Median age was 62.0 years, 50.4% were male, 61.9% had stage IV FL, and 45.1% were classified as high-risk FLIPI. Of the 110 pts who were eligible for G SDI from C2, no pt experienced a Gr ≥3 IRR with SDI in C2 (Table). One pt experienced a Gr 3 IRR with SDI in C5, presenting hypertension. All other IRRs with SDI were Gr 1/2. No Gr 4/5 IRRs were reported. Other AEs were similar to those observed in previous studies. At the clinical cut-off date, 104 pts had a CT imaging-based response assessment at EOI and 9 pts had no response assessment; 76/113 (67.3%) had a complete response, 22 (19.5%) had a partial response, and six (5.8%) had PD. Conclusions: In GAZELLE, G SDI in C2 and beyond appeared to be safe. No Gr 3 IRRs were observed in C2 and only one Gr 3 IRR was reported in subsequent cycles. The safety profile of G SDI was comparable with the established profile of G in advanced FL. Clinical trial information: NCT03817853. [Table: see text]

Obinutuzumab plus lenalidomide (GALEN) in advanced, previously untreated follicular lymphoma in need of systemic therapy

Blood ◽  
2021 ◽  
Author(s):  
Emmanuel Bachy ◽  
Roch Houot ◽  
Pierre Feugier ◽  
Krimo Bouabdallah ◽  
Reda Bouabdallah ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Safety Profile ◽  
Response Rate ◽  
Metabolic Response ◽  
Complete Response ◽  
Tumor Burden ◽  
Common Adverse Event ◽  
Induction Treatment ◽  
High Tumor Burden ◽  
Grade 3

Obinutuzumab and lenalidomide (GALEN) is an active immunomodulatory combination with a manageable safety profile in multiple types of lymphoma. We report efficacy and safety results for the phase 2 GALEN study in previously-untreated patients with advanced follicular lymphoma (FL). Eligible patients aged ≥ 18 years had ECOG PS ≤ 2, high-tumor burden, grade 1-3a FL. Induction treatment was obinutuzumab (1000 mg IV, days 8/15/22, cycle 1; day 1, cycles 2-6) plus lenalidomide (20 mg/day, days 1-21, cycle 1; days 2-22, cycles 2-6) for 6 cycles. Maintenance included obinutuzumab (1000 mg every 2 cycles) plus lenalidomide (10 mg, days 2-22) for ≤ 12 cycles (year 1) followed by obinutuzumab (1000 mg every 56 days) for 6 cycles (year 2). The primary endpoint was complete response rate (CRR) after induction per IWG 1999 criteria. From October 2015 to February 2017, 100 patients were enrolled. CRR after induction was 47% and overall response rate (ORR) 92%. Post-hoc analyses per 2014 Lugano classification including patients with missing bone marrow assessments identified an additional 13 patients fulfilling CRR criteria, resulting in a complete metabolic response of 80% and ORR of 94%. At a median follow-up of 3.7 years, 3-year progression-free and overall survival were 82% and 94%, respectively. The most common adverse event was neutropenia (48% any-grade; 47% grade ≥ 3) but only 2% of patients presented febrile neutropenia; others were mainly grade ≤ 2. No other specific grade ≥3 toxicity occurred at a frequency higher than 3%. Overall, these results demonstrated promising clinical efficacy for the chemo-free backbone obinutuzumab and lenalidomide in previously untreated, high tumor burden FL patients. Except for neutropenia, the safety profile of the combination is remarkable. The study was registered with ClinicalTrials.gov, number NCT01582776

scholarly journals Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy

Blood ◽  
2019 ◽  
Vol 134 (4) ◽  
pp. 353-362 ◽  
Author(s):  
Emanuele Zucca ◽  
Stephanie Rondeau ◽  
Anna Vanazzi ◽  
Bjørn Østenstad ◽  
Ulrich J. M. Mey ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinical Cancer Research ◽  
International Prognostic Index Score ◽  
First Line Therapy ◽  
Phase 2 Trial ◽  
Grade 3

Abstract The SAKK 35/10 phase 2 trial, developed by the Swiss Group for Clinical Cancer Research and the Nordic Lymphoma Group, compared the activity of rituximab vs rituximab plus lenalidomide in untreated follicular lymphoma patients in need of systemic therapy. Patients were randomized to rituximab (375 mg/m2 IV on day 1 of weeks 1-4 and repeated during weeks 12-15 in responding patients) or rituximab (same schedule) in combination with lenalidomide (15 mg orally daily for 18 weeks). Primary end point was complete response (CR)/unconfirmed CR (CRu) rate at 6 months. In total, 77 patients were allocated to rituximab monotherapy and 77 to the combination (47% poor-risk Follicular Lymphoma International Prognostic Index score in each arm). A significantly higher CR/CRu rate at 6 months was documented in the combination arm by the investigators (36%; 95% confidence interval [CI], 26%-48% vs 25%; 95% CI, 16%-36%) and confirmed by an independent response review of computed tomography scans only (61%; 95% CI, 49%-72% vs 36%; 95% CI, 26%-48%). After a median follow-up of 4 years, significantly higher 30-month CR/CRu rates and longer progression-free survival (PFS) and time to next treatment (TTNT) were observed for the combination. Overall survival (OS) rates were similar in both arms (≥90%). Toxicity grade ≥3 was more common in the combination arm (56% vs 22% of patients), mainly represented by neutropenia (23% vs 7%). Addition of lenalidomide to rituximab significantly improved CR/CRu rates, PFS, and TTNT, with expected higher, but manageable toxicity. The excellent OS in both arms suggests that chemotherapy-free strategies should be further explored. This trial was registered at www.clinicaltrials.gov as #NCT01307605.

Combination of Bortezomib, Melphalan, Prednisone and Thalidomide (VMPT) for Relapsed Multiple Myeloma: Results of a Phase I/II Clinical Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 407-407 ◽  
Author(s):  
Antonio Palumbo ◽  
Maria Teresa Ambrosini ◽  
Giulia Benevolo ◽  
Patrizia Pregno ◽  
Norbert Pescosta ◽  
...  
Keyword(s):  
Partial Response ◽  
Phase I ◽  
Response Rate ◽  
Oral Prednisone ◽  
Progression Free Survival ◽  
Complete Response ◽  
Second Line ◽  
Open Label ◽  
Free Survival ◽  
Line Of Therapy

Abstract BACKGROUND: In newly diagnosed patients, the addition of thalidomide or bortezomib (Velcade™) to the standard oral melphalan/prednisone combination significantly increased response rate and event-free survival. In this multicenter, open-label, non randomized, phase I/II trial, the safety/efficacy profile of the 4 drug combination, bortezomib (Velcade™), melphalan, prednisone, and thalidomide (VMPT) was evaluated in patients with relapsed/refractory myeloma. METHODS: Bortezomib was administered by IV bolus on days 1, 4, 15, 22 at three dose levels: in the first cohort (10 patients) at 1.0 mg/m2; in the second cohort (10 patients) at 1.3 mg/m2and in the third cohort (10 patients) at 1.6 mg/m2. Oral melphalan was administered at 6 mg/m2 on days 1–5, oral prednisone at 60 mg/m2 on days 1–5. Thalidomide was delivered at 50 mg on days 1–35. Each course was repeated every 35 days for a total of 6 courses. RESULTS: Thirty patients, median age 66 years (range 38–79), with relapsed or refractory myeloma were enrolled. Fourteen patients received VMPT as second line of therapy, 16 as third line. Twenty patients received prior autologous transplant, 10 conventional chemotherapy and 9 thalidomide-based regimens. After a median of 6 courses, 20 patients (67%) achieved a partial response (PR) including 13 patients (43%) who achieved at least a very good partial response (VGPR). Among patients who received VMPT as second line treatment, the PR rate was 79%, and the immunofixation negative complete response rate 36%. The 1-year progression-free survival was 61%, and the 1-year survival from study entry was 84%. Grade 3 non-hematological adverse events included: infections (5 patients), fatigue (1), vasculitis (1) and peripheral neuropathy (2); no grade 4 toxicities were recorded. CONCLUSIONS: Initial results showed that VMPT is an effective salvage therapy with a high proportion of responses. Toxicities were manageable. The incidence of neurotoxicities was unexpectedly low.

Randomized phase II study of the safety and efficacy of a human anti-αv integrin monoclonal antibody (CNTO 95) alone and in combination with dacarbazine in patients with stage IV metastatic melanoma: 12-month results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9029-9029
Author(s):  
C. Loquai ◽  
A. Pavlick ◽  
D. Lawson ◽  
R. Gutzmer ◽  
J. Richards ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Research And Development ◽  
Metastatic Melanoma ◽  
Single Agent ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Complete Response ◽  
Open Label ◽  
Safety And Efficacy ◽  
To Receive

9029 Objectives: Evaluate the safety and efficacy of CNTO 95, a human anti-αv integrin monoclonal antibody, when administered alone or in combination with dacarbazine (DTIC). Methods: Patients with Stage IV metastatic melanoma were randomized 1:1:1:1 to receive 5 or 10mg/kg CNTO 95 alone, or DTIC (1000mg/m2) + either 10mg/kg CNTO 95 or placebo administered intravenously once every 3 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. DTIC arms were blinded; single-agent arms were open-label. The primary endpoint was progression free survival (PFS); secondary endpoints included partial response (PR), complete response (CR), stable disease (SD) and overall survival (OS). Major safety endpoints included the incidence of adverse events (AEs) and serious AEs (SAEs). Results: Patients were randomized to receive 5mg/kg CNTO 95 (n=32), 10mg/kg CNTO 95 (n=33), CNTO 95+DTIC (n=32), or placebo+DTIC (n=32). Baseline demographics were similar across groups. The median PFS for CNTO 95+DTIC was 75 days, placebo+DTIC was 54 days and both CNTO 95 alone arms were 42 days. Six patients achieved PR (2–10mg/kg CNTO 95, 1-CNTO 95+DTIC, 3-placebo+DTIC); one patient achieved CR (CNTO 95+DTIC). A higher proportion (43.3%) of patients achieved SD ≥ 12 wks in the CNTO 95+DTIC group compared with the other 3 groups (<20.0%). The median survival was 11.0 months for the patients in the CNTO 95+DTIC arm, 9.8 months and 14.9 months for the 5mg/kg and 10mg/kg arms, and 8.0 months for those in the DTIC control arm. The most common AEs were headache, nausea, fatigue, pyrexia, vomiting and transient uveitic reactions. Three patients (1–5mg/kg, 2-CNTO 95+DTIC) discontinued treatment due to AEs. A higher proportion of patients experienced SAEs in the placebo+DTIC group (29.0%) than in the 5mg/kg (12.9%), 10mg/kg (16.2%) or CNTO 95+DTIC (18.8%) groups. Conclusions: CNTO 95 alone or combined with DTIC was generally well tolerated. In patients with Stage IV metastatic melanoma, a trend toward improvement in PFS, OS and disease control was demonstrated with CNTO 95+DTIC. Centocor, Centocor Research and Development, Inc. Centocor Research and Development, Inc. Johnson & Johnson Centocor Research and Development, Inc. No significant financial relationships to disclose.

Efficacy of vemurafenib in patients (pts) with non-small cell lung cancer (NSCLC) with BRAFV600 mutation.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9074-9074 ◽  
Author(s):  
Vivek Subbiah ◽  
Radj Gervais ◽  
Gregory J. Riely ◽  
Antoine Hollebecque ◽  
Jean-Yves Blay ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Braf Mutations ◽  
Open Label ◽  
Braf Inhibition ◽  
Duration Of Response ◽  
Secondary Endpoints ◽  
Prior Systemic Therapy ◽  
Grade 3

9074 Background: BRAFV600 mutations occur in 1–2% of pts with NSCLC. We previously reported the efficacy of vemurafenib, a selective BRAFV600 inhibitor, in BRAF mutation-positive non-melanoma tumors (VE-BASKET study). We now present final data for the expanded NSCLC cohort. Methods: This open-label, histology-independent, phase 2 study included 6 prespecified cohorts (including NSCLC) plus one ‘all-others’ cohort. Pts received vemurafenib (960 mg bid) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (RECIST v1.1). Secondary endpoints included best overall response rate, duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Because the pre-specified clinical benefit endpoint was met in the initial NSCLC cohort, the cohort was expanded. ClinicalTrials.gov identifier NCT01524978. Results: Database lock was 12 Jan 2017. Of 208 pts enrolled at 25 centers worldwide, 62 pts had NSCLC: median age 65 years; 56% male; 13% had no prior systemic therapy; 50% had ≥2 prior therapies. Responses were seen in previously treated and untreated pts (Table). The most common all-grade adverse event (AE) was nausea (40%); grade 3–5 AEs included keratoacanthoma (15%) and squamous cell carcinoma of the skin (15%). Six pts discontinued vemurafenib due to AEs; two had non-treatment-related fatal AEs. Conclusions: Vemurafenib showed evidence of encouraging efficacy in pts with NSCLC with BRAFV600 mutation, with prolonged PFS in previously untreated pts; median OS was not estimable due to ongoing responses. The safety profile of vemurafenib was similar to that seen in melanoma studies. Our results suggest a role for BRAF inhibition in NSCLC with BRAF mutations. Clinical trial information: NCT01524978. [Table: see text]

Weekly Topotecan for Recurrent Ovarian, Fallopian Tube and Primary Peritoneal Carcinoma: Tolerability and Efficacy Study—The Israeli Experience

2013 ◽  
Vol 23 (3) ◽  
pp. 475-480 ◽  
Author(s):  
Tamar Safra ◽  
Tara Berman ◽  
Adelya Yachnin ◽  
Ilan Bruchim ◽  
Mihai Meirovitz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Partial Response ◽  
Clinical Benefit ◽  
Response Rate ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Tubal Cancer ◽  
Grade 3

ObjectivesThe purpose of this study was to assess the clinical activity and toxicity of weekly topotecan in a large cohort of epithelial ovarian (EOC), primary peritoneal (PPC), and tubal cancer patients.MethodsRecords of patients with recurrent EOC, PPC, and tubal cancer who were treated with weekly topotecan (4.0 mg/m2 on days 1, 8, and 15 on a 28-day cycle) after failure of more than 1 prior regimen were retrospectively reviewed in 8 centers in Israel.ResultsTwo hundred four patients were evaluated for efficacy and toxicity. Median age was 62 years (range, 27–89 years); 121 (59.3%) were platinum sensitive. Patients were exposed to a median of 2 previous lines (range, 1–9), and 48.5% received only 1 prior chemotherapy regimen. Median follow-up was 15.5 months (range, 2.5–112 months). Overall response rate was 26.5%, of which 11 patients (5.4%) had complete response, and 43 patients (21.1%) had partial response. Clinical benefit rate (complete response + partial response + stable disease) was 65.7%. Median progression-free survival was 4.0 months (95% confidence interval [CI], 3.5–4.5 months). There was no significant difference between platinum-sensitive and platinum-resistant patients regarding response rate or progression-free survival. Median overall survival from disease diagnosis was 45.0 months (95% CI, 40.04–49.6 months) and 16.0 months (95% CI, 12.3–19.7 months) from initiation of topotecan therapy. Overall survival was significantly different between patients with platinum-sensitive and platinum-resistant disease (19.9 vs 10.8 months, respectively, P = 0.003; 95% CI, 8.1–16.3 months). Multivariate analysis showed that only platinum sensitivity and topotecan line were associated with overall survival. Weekly topotecan was well tolerated—with only 16.7% of patients experiencing grade 3 to 4 hematologic toxicities. There were no other grade 4 toxicities, and only 6.9% grade 3 toxicities.ConclusionsIn this large cohort of recurrent EOC, PPC, and tubal cancer, weekly topotecan was well tolerated with good clinical benefit rate, comparable to previous studies.

Sign in / Sign up

Export Citation Format

Share Document