Second-line chemotherapy (CT) with or without bevacizumab (BV) in metastatic colorectal cancer (mCRC) patients (pts) who progressed to a first-line treatment containing BV: Updated results of the phase III “BEBYP” trial by the Gruppo Oncologico Nord Ovest (GONO).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3615-3615 ◽  
Author(s):  
Gianluca Masi ◽  
Fotios Loupakis ◽  
Lisa Salvatore ◽  
Chiara Cremolini ◽  
Lorenzo Fornaro ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Free Survival ◽  
Phase Iii Study ◽  
Reported Data ◽  
To Receive ◽  
Clinical Trial Information

3615 Background: Retrospective data suggested that the continuation of BV with second-line CT beyond progression (PD) in pts who received BV in first-line can improve the outcome. Recently, results of the AIO/AMG ML18147 study demonstrated an improved overall survival (OS) by continuing BV beyond PD. Methods: This phase III study randomized pts with measurable mCRC treated in first-line with BV plus fluoropyrimidine, FOLFIRI, FOLFOX or FOLFOXIRI, to receive in second-line mFOLFOX6 or FOLFIRI (depending on first-line CT) with or without BV. The primary end-point was progression free survival (PFS).To detect a HR for PFS of 0.70 with an α and β error of 0.05 and 0.20 respectively, the study required 249 events. Assuming an accrual time of 24 months (mos) and a follow up of 12 mos we planned to randomize 262 pts. Results: Considering the results of the AIO/AMG ML18147 trial, the study accrual was stopped prematurely. A total of 185 pts were randomized and 184 pts were included in the ITT analysis (1 pt randomized in error). Pts characteristics were (arm A/arm B): number 92/92, gender M75%-F25%/M57%-F43%, median age 66 (38-75)/62 (38-75) years, PS=0 82%/82%, multiple site of disease 76%/77%. At a median follow up of 18 mos the study met its primary endpoint by improving PFS in the BV arm. We updated results and at a median follow up of 22 mos the improvement in PFS for the experimental arm was confirmed with a median PFS of 5.2 mos for arm A and 6.7 mos for arm B (HR=0.66; 95% CI 0.49–0.90; unstratified p=0.0072). Subgroup analyses showed a consistent benefit in all subgroups including gender (F: HR=0.63; M: HR=0.72) and first-line PFS (≤10 mos: HR=0.57; >10 mos: HR=0.71). Response rates (RECIST) were 18% and 21% (p=0.71). Toxicity profile was consistent with previously reported data. The OS data are still immature, with 56 events in arm A and 54 in arm B and the median OS is 16.0 mos and 16.5 mos respectively (HR=0.83; 95% CI 0.57-1.22; unstratified p=0.34). Conclusions: This study demonstrates an improvement in PFS by continuing BV in second-line in pts who had received CT+BV in first-line. Clinical trial information: NCT00720512.

scholarly journals Final Results of the IELSG-19 Randomized Trial of Mucosa-Associated Lymphoid Tissue Lymphoma: Improved Event-Free and Progression-Free Survival With Rituximab Plus Chlorambucil Versus Either Chlorambucil or Rituximab Monotherapy

2017 ◽  
Vol 35 (17) ◽  
pp. 1905-1912 ◽  
Author(s):  
Emanuele Zucca ◽  
Annarita Conconi ◽  
Giovanni Martinelli ◽  
Reda Bouabdallah ◽  
Alessandra Tucci ◽  
...  
Keyword(s):  
Overall Survival ◽  
Randomized Trial ◽  
Lymphoid Tissue ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Final Sample ◽  
Phase Iii Study ◽  
To Receive

Purpose There is no consensus on the optimal systemic treatment of patients with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The IELSG-19 phase III study, to our knowledge, was the first such study to address the question of first-line treatment in a randomized trial. Patients and Methods Eligible patients were initially randomly assigned (1:1 ratio) to receive either chlorambucil monotherapy (6 mg/m2/d orally on weeks 1 to 6, 9 to 10, 13 to 14, 17 to 18, and 21 to 22) or a combination of chlorambucil (same schedule as above) and rituximab (375 mg/m2 intravenously on day 1 of weeks 1, 2, 3, 4, 9, 13, 17, and 21). After the planned enrollment of 252 patients, the protocol was amended to continue with a three-arm design (1:1:6 ratio), with a new arm that included rituximab alone (same schedule as the combination arm) and with a final sample size of 454 patients. The main end point was event-free survival (EFS). Analysis of chlorambucil versus the combination arm was performed and reported separately before any analysis of the third arm. Results At a median follow-up of 7.4 years, addition of rituximab to chlorambucil led to significantly better EFS (hazard ratio, 0.54; 95% CI, 0.38 to 0.77). EFS at 5 years was 51% (95% CI, 42 to 60) with chlorambucil alone, 50% (95% CI, 42 to 59) with rituximab alone, and 68% (95% CI, 60 to 76) with the combination ( P = .0009). Progression-free survival was also significantly better with the combination ( P = .0119). Five-year overall survival was approximately 90% in each arm. All treatments were well tolerated. No unexpected toxicities were recorded. Conclusion Rituximab in combination with chlorambucil demonstrated superior efficacy in mucosa-associated lymphoid tissue lymphoma; however, improvements in EFS and progression-free survival did not translate into longer overall survival.

Phase III study of lapatinib (L) plus trastuzumab (T) and aromatase inhibitor (AI) vs T+AI vs L+AI in postmenopausal women (PMW) with HER2+, HR+ metastatic breast cancer (MBC): ALTERNATIVE.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1004-1004 ◽  
Author(s):  
William John Gradishar ◽  
Roberto Hegg ◽  
Seock-Ah Im ◽  
In Hae Park ◽  
Sergei Tjulandin ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Clinical Benefit ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
To Receive ◽  
Clinical Trial Information

1004 Background: Combination ofHER2-targeted therapy+AI improved clinical benefit in patients (pts) with HER2+, HR+ MBC vs AI alone in two previous trials, median progression free survival (mPFS) 4.8 vs 2.4 mo (TAnDEM), and 8.2 vs 3.0 mo (EGF30008). Dual HER2 blockade enhances clinical benefit vs single HER2 blockade. This study evaluated the safety and efficacy of dual vs single HER2 blockade (L+T vs T/L)+AI in HER2+, HR+ MBC progressing on (neo)adjuvant/first-line T+chemotherapy (CT). HER2 and HR status were assessed for eligibility at local lab. Methods: PMW were randomized 1:1:1 to receive T (8mg/kg followed by 6mg/kg IV Q3W)+L (1000mg/d)+AI or T+AI or L (1500mg/d)+AI. AI was per investigator’s choice. Pts were excluded if they were intended for CT. The primary endpoint was to assess superiority of PFS with L+T vs T. Secondary endpoints included PFS (L vs T), overall survival (OS), overall response rate (ORR), and safety. Results: 369 pts were enrolled; current analysis included 355 pts (data cutoff, March 11, 2016); L+T (n = 120), T (n = 117) or L (n = 118). Final PFS data were analyzed after 137 events. Baseline characteristics were balanced across all treatment (tx) arms. The primary endpoint was met; superior PFS was observed with L+T vs T (mPFS, 11 vs 5.7 mo; HR = 0.62, 95% CI [0.45, 0.88], P= 0.0064). This benefit of L+T was consistent in key subgroups. mPFS with L vs T was 8.3 vs 5.7 mo (HR = 0.71, 95% CI [0.51, 0.98], P= 0.0361). ORR with L+T, T, and L was 32%, 14%, and 19% respectively. OS data are immature. Most common adverse events (AEs) with L+T, T and L (≥15%, any arm) were diarrhea (69%, 9%, 51%), rash (36%, 2%, 28%), nausea (22%, 9%, 22%), and paronychia (30%, 0, 15%). Hepatic abnormalities of > 3 ULN ALT/AST levels were noted in 4%, 6%, and 16% respectively. Incidence of tx-related SAEs was 5%, 2%, and 4% and on-tx deaths was 3%, 4%, and 5%, respectively. Conclusions: Dual HER2 blockade with L+T+AI showed superior PFS benefit vs T+AI, in pts with HER2+, HR+ MBC. Incidence of AEs was increased with L+T. This combination can potentially offer an effective CT-sparing tx option in subgroup of HER2+, HR+ pts without aggressive disease and who are not candidates for CT. Clinical trial information: 2010-019577-16.

Consolidation with Alemtuzumab Improves Progression-Free Survival in Patients with Chronic Lymphocytic Leukemia (CLL) in First Remission - Long-Term Follow-Up of a Randomized Phase III Trial of the German CLL Study Group (GCLLSG).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 33-33 ◽  
Author(s):  
C. Schweighofer ◽  
M. Ritgen ◽  
B. Eichhorst ◽  
R. Busch ◽  
M. Kneba ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Consolidation Therapy ◽  
First Line ◽  
Phase Iii Trial ◽  
Free Survival ◽  
To Receive ◽  
Line Chemotherapy

Abstract Purpose: Alemtuzumab (MabCampath) is a humanized monoclonal antibody that targets the CD52 antigen, which is highly expressed on most human B and T lymphocytes. Alemtuzumab has shown considerable activity in both relapsed/refractory CLL and in the frontline treatment setting. In a recent study, treatment with single-agent alemtuzumab induced MRD-negative remissions in 20% of patients with relapsed/refractory CLL (Moreton et al JCO 2005;23:2971–2979). Other studies suggest that MRD negativity can also be attained when alemtuzumab is administered as consolidation for patients with CLL who achieve incomplete initial responses to chemotherapy. Here, we report our long-term experience within a randomized phase III trial that investigates the role of alemtuzumab for consolidation therapy in patients with previously untreated CLL. Methods: Pts in complete or partial remission after induction chemotherapy, with either fludarabine (F) or fludarabine plus cyclophosphamide (FC), were randomized to receive either alemtuzumab 30 mg, 3 times a week for ≤12 wks or no further treatment. Of 21 eligible pts, who had responded to induction with F or FC (1 CR, 1 nPR, 9 PRs), 11 pts (median age: 60 years) randomized to receive alemtuzumab consolidation and 10 to the observation arm. Pts in the alemtuzumab arm received standard premedication and infection prophylaxis with famciclovir and trimethoprim/sulfamethoxazole. Results: After a median follow-up of 48 months, calculated from time of randomization within this consolidation trial, progression-free survival (PFS) was significantly improved for pts who received alemtuzumab consolidation compared to those who received no further treatment (median PFS not reached versus 20.6 months, P = 0.004). PFS from the beginning of induction therapy with F or FC is also significantly greater for patients in the alemtuzumab consolidation arm versus the observation arm. So far, 3 of 11 pts presented with disease progression after alemtuzumab consolidation compared with 8/10 progressing pts in the observation arm. Differences in PFS between both arms were not associated with disease stage before first line treatment, type of first line chemotherapy (F vs. FC) or response status before initiation of consolidation therapy (CR vs. nPR vs. PR). Correlations between achievement of MRD negative responses and PFS is still under investigation and is planned for presentation. With the exception of 2 patients (1 pt in each arm) all patients remain alive. The study was stopped prematurely due to severe infections (7 CTC III infections, which included 4 CMV reactivations, 1 CTC IV infection) in 7/11 patients being treated with alemtuzumab. However, these infections were successfully treated, not associated with the cumulative dose of alemtuzumab, and no late complications of consolidation therapy have been observed. Conclusions: Although based on few pts due to incomplete accrual, long-term PFS was significantly prolonged in patients with CLL receiving alemtuzumab consolidation after first line chemotherapy with F or FC. An ongoing phase I/II trial of the GCLLSG (CLL2i) is currently evaluating the optimal dose and schedule of alemtuzumab in CLL pts after fludarabine-based chemotherapy.

scholarly journals Sequential Treatment of Metastatic Adenocarcinoma of the Pancreatic Duct with Liver Metastasis Following the NAPOLI-1 Study Protocol with nal-Irinotecan plus 5-FU in the Second Line

2020 ◽  
Vol 13 (1) ◽  
pp. 79-84
Author(s):  
Dilara Akhoundova Sanoyan ◽  
Cäcilia S. Reiner ◽  
Panagiota Papageorgiou ◽  
Alexander R. Siebenhüner
Keyword(s):  
Systemic Treatment ◽  
Sequential Treatment ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Curative Surgery ◽  
To Receive

Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at an advanced or metastatic stage, when curative surgery is not recommended. Therefore, the prognosis is poor for this dismal disease, with only 1–2% of the patients reaching the 5-year survival follow-up. Current advances in systemic treatment with gemcitabine regimens, specifically polychemotherapy with gemcitabine plus nab-paclitaxel or other multidrug regimens such as FOLFIRINOX in the first line, have improved disease control over time. This higher efficacy of systemic treatment enables metastatic PDAC patients to receive second-line treatment more often nowadays. Currently, there is only one regimen for second-line treatment approved by the EMA, FDA, and Swissmedic, based on the phase III NAPOLI-1 study. In this case report, we present an outstanding response to sequential treatment with gemcitabine plus nab-paclitaxel followed by second-line treatment with nal-irinotecan plus 5-fluorouracil.

Efficacy of avelumab plus axitinib (A + Ax) versus sunitinib (S) by number of IMDC risk factors and tumor sites at baseline in advanced renal cell carcinoma (aRCC): Extended follow-up results from JAVELIN Renal 101.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 302-302
Author(s):  
Yoshihiko Tomita ◽  
Robert J. Motzer ◽  
Toni K. Choueiri ◽  
Brian I. Rini ◽  
Hideaki Miyake ◽  
...  
Keyword(s):  
Risk Factors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Risk Groups ◽  
Phase Iii ◽  
Once Daily ◽  
Free Survival ◽  
To Receive

302 Background: In the phase III JAVELIN Renal 101 trial (NCT02684006), A + Ax demonstrated progression-free survival (PFS) and objective response rate (ORR) benefit across IMDC risk groups (favorable, intermediate, and poor) vs S in patients with previously untreated aRCC. Here we report efficacy of A + Ax vs S by number of IMDC risk factors (0, 1, 2, 3, and 4-6) and target tumor sites (1, 2, 3, and ≥4) at baseline from the second interim analysis of overall survival (OS). Methods: Patients were randomized 1:1 to receive A 10 mg/kg intravenously every 2 wk + Ax 5 mg orally twice daily or S 50 mg orally once daily for 4 wk (6-wk cycle). PFS and ORR per independent central review (RECIST 1.1) and OS were assessed. Results: At data cut-off (Jan 2019), median (m) follow-up for OS and PFS was 19.3 vs 19.2 mo and 16.8 vs 15.2 mo for the A + Ax vs S arm, respectively. The table shows OS, PFS, and ORR by number of IMDC risk factors and target tumor sites at baseline. A + Ax generally demonstrated efficacy benefit vs S across subgroups. Conclusions: With extended follow-up, A + Ax generally demonstrated efficacy benefit vs S across the number of IMDC risk factors and tumor sites at baseline in aRCC. OS was still immature; follow-up for the final analysis is ongoing. Clinical trial information: NCT02684006 . [Table: see text]

Patient Outcomes with Proteosome Inhibitor Bortezomib in Multiple Myeloma at an English District General Hospital

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5745-5745
Author(s):  
Anil Vaikunth Kamat ◽  
Tariq Shafi ◽  
Raphael A. Ezekwesili
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Second Primary ◽  
Second Line ◽  
First Line ◽  
Free Survival ◽  
Grade 3 ◽  
Second Primary Malignancies

Abstract Bortezomib is a targeted proteosome inhibitor licensed & approved for in multiple myeloma both as first line and in relapsed setting. This is a retrospective non experimental cross sectional quantitative comparative group study using clinical case notes, laboratory & pharmacy records for patients treated with Bortezomib in 2011 & 2012. Outcomes studied included remission status, adverse events, progression free survival and overall survival at follow up. The study also looked at the comparative responses of cohort of patients administered Bortezomib through intravenous & subcutaneous route. The cohort consisted of 33 patients, 21 male, 11 female, median age 71 years, first line 10 patients, second line 23 , median number of cycles in 2011 & 2012 – first line 3 & 8 , second line 5 & 4, respectively. In 2011, 8 received intravenous treatment, 9 were switched from intravenous to subcutaneous route whilst all patients from 2012 received subcutaneous Bortezomib. The most frequently used regimen was Bortezomib Dexamethasone ( VD). The overall response rate ( ORR >/= Minor Response) was: First line 70% (7/10) ; Second line 47.8% ( 11/23); median PFS ( Figure 1) 6 months ( First line: 7 months ; Second line : 6 months) and median overall survival ( Figure 2) at follow up: 9 months ; 39.4 % ( 13/33) First line 8.5 months, Second line 11 months. Subcutaneous Bortezomib was equivalent to intravenous Bortezomib in terms of efficacy & tolerance. Of 33 patients, there were 12 dose reductions. Adverse events reported included: peripheral Neuropathy - grade 3 - 6% ( all grades 27.3%); Diarrhoea - grade 3 - 3% (all grades 6%); Nausea / Vomiting - grade 3 - 3% ( all grades 6%) and Second Primary Malignancies - 12% ( 4 of 33). Mortality at follow up was 20 patients from cohort of 33 ; causes included disease progression in 11, second primary malignancy with disease progression in 4, COPD 2, Systemic Amyloidosis 2, Tuberculosis 1 , Multiple co morbidities 1 and Asthma with mechanical failure in single patient. Second primary malignancies ( 4/33) included Prostate carcinoma ( 1), Renal Cell Carcinoma (1), Neuroendocrine tumour ( 1 ) and Unknown Primary in single patient. Beyond second line treatment, majority (14 of 23 patients; 60.9 %) did not have further active treatment. These data indicate that patient outcomes were modest compared to published data from VISTA and APEX trials. Majority of patients did not have further active treatment beyond second line which suggests the most effective treatment strategy should be used upfront as patients may not be fit to have further lines of therapy despite availability of recently introduced novel targeted agents. A higher percentage of second primary malignancies were noticed in this cohort which should be an area of further clinical research. Figure 1: Progression free survival with Bortezomib as first line & second line in multiple myeloma Figure 1:. Progression free survival with Bortezomib as first line & second line in multiple myeloma Figure 2: Overall survival with Bortezomib as first line & second line in multiple myeloma Figure 2:. Overall survival with Bortezomib as first line & second line in multiple myeloma Disclosures No relevant conflicts of interest to declare.

Results of a phase III, randomized, double-blind, placebo-controlled trial of pegfilgrastim (PEG) in patients (pts) receiving first-line FOLFOX or FOLFIRI and bevacizumab (B) for colorectal cancer (CRC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3575-3575
Author(s):  
Tamas Pinter ◽  
Esteban Abella ◽  
Alvydas Cesas ◽  
Adina Croitoru ◽  
Jochen Decaestecker ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Double Blind ◽  
Free Survival ◽  
Clinically Significant ◽  
Grade 3

3575 Background: The literature reports that adding biologics to chemotherapy (ctx) may increase the incidence of clinically significant neutropenia. his trial was conducted to evaluate the efficacy of PEG in reducing the incidence of febrile neutropenia (FN) in pts with locally-advanced (LA) or metastatic (m)CRC receiving first-line treatment with either FOLFOX/B or FOLFIRI/B. Methods: Key eligibility: ≥ 18 years old; measurable, nonresectable CRC per RECIST 1.1. Pts were randomly assigned 1:1 to either placebo or 6 mg PEG ~24 h after ctx/B. The study treatment period included four Q2W cycles, but pts could continue their assigned regimen until progression. Pts were stratified by region (North America vs rest of world), stage (LA vs mCRC), and ctx (FOLFOX vs FOLFIRI). Estimated sample size (N = 800) was based on the expected incidence of grade 3/4 FN (primary endpoint) across the first 4 cycles of ctx/B, powered for PEG superiority over placebo. Other endpoints included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: 845 pts were randomized (Nov 2009 to Jan 2012) and received study treatment; 783 pts completed 4 cycles of ctx/B. Median age was 61 years; 512 (61%) pts were male; 819 (97%) had mCRC; 414 (49%) received FOLFOX, and 431 (51%) received FOLFIRI. Grade 3/4 FN (first 4 cycles) for placebo vs PEG was 5.7% vs 2.4%; OR 0.41; p = 0.014. A similar incidence of other ≥ grade 3 adverse events was seen in both arms (28% placebo; 27% PEG). See table for additional results. Conclusions: PEG significantly reduced the incidence of grade 3/4 FN in this pt population receiving standard ctx/B for CRC. Follow-up is ongoing. Clinical trial information: NCT00911170. [Table: see text]

An update on BREAK-3, a phase III, randomized trial: Dabrafenib (DAB) versus dacarbazine (DTIC) in patients with BRAF V600E-positive mutation metastatic melanoma (MM).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9013-9013 ◽  
Author(s):  
Axel Hauschild ◽  
Jean Jacques Grob ◽  
Lev V. Demidov ◽  
Thomas Jouary ◽  
Ralf Gutzmer ◽  
...  
Keyword(s):  
Median Overall Survival ◽  
Braf Inhibitor ◽  
Progression Free Survival ◽  
Braf V600e ◽  
Phase Iii ◽  
Primary Analysis ◽  
Free Survival ◽  
Independent Review ◽  
Clinical Trial Information

9013 Background: Dabrafenib is a selective BRAF inhibitor with demonstrated efficacy in BRAF V600E-positive mutation in MM. The primary analysis of BREAK-3 (NCT01227889) compared progression-free survival (PFS) in patients (pts) with BRAF V600E-positive mutation MM treated with dabrafenib or DTIC. Methods: Median PFS for dabrafenib of 5.1 months (mo) and study methods were previously described (Hauschild A, et al. Lancet. 2012,380:358–365). Independent review ended at the primary analysis. PFS was updated in Jun 2012 at median follow-up of 10.5 mo for dabrafenib (67% of PFS events), and 9.9 mo for DTIC. Median overall survival (OS) was not reached, so another analysis of OS and safety was performed with data as of Dec 2012, at which time the median follow-up was 15.2 (dabrafenib) and 12.7 (DTIC) mo. PFS of subjects who crossed over was also evaluated at that time. Results: PFS hazard ratio was 0.37 [95% CI; 0.23, 0.57]; median PFS was 6.9 mo dabrafenib and 2.7 mo DTIC. In Dec 2012, 36/63 DTIC pts crossed over; median PFS was 4.3 [95% CI; 4.1, 6.1] mos. OS is presented in the Table.The four most common adverse events (AE) on the dabrafenib arm were hyperkeratosis (39%), headache (35%), arthralgia (35%), and pyrexia (32%). Serious AEs ≥ 5% on the dabrafenib arm included cutaneous squamous cell carcinoma/keratoacanthoma (10%) and pyrexia (5%). Conclusions: Longer follow-up confirms the benefits of dabrafenib on PFS and response rate. Median OS in the dabrafenib arm was over 18 mo and over 15 mo in the DTIC arm. OS results are confounded by crossover of DTIC pts to dabrafenib and likely by subsequent therapy after progression. The effects of subsequent therapy results will be investigated. The safety profile had no significant changes. Clinical trial information: NCT01227889. [Table: see text]

Phase II study of sequential first-line pazopanib (PAZ) followed by everolimus (EVE) in patients (pts) with advanced or metastatic renal cell carcinoma (RCC) (CATChEz Study).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 648-648 ◽  
Author(s):  
Paul L. de Souza ◽  
Shirley Wong ◽  
Sanjeev Sewak ◽  
Dusan Kotasek ◽  
Bhumsuk Keam ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Free Survival ◽  
Anticancer Treatment ◽  
Secondary Endpoints ◽  
Prior Systemic Therapy ◽  
Grade 3 ◽  
Metastatic Rcc

648 Background: EVE following failure of sorafenib or sunitinib for RCC was first approved by the FDA in 2009. CATChEz (NCT01545817) was designed to test the activity of EVE following first-line PAZ in pts with advanced or metastatic RCC who had not received prior systemic therapy. Methods: From 2012 to 2016, pts received first-line PAZ followed by EVE until progressive disease (PD), death, unacceptable toxicity, consent withdrawal, or study termination. Pts with PD during or within 6 months of stopping PAZ were eligible for EVE. Pts off study treatment were evaluated for PD, survival, and updates on anticancer treatment every 8 weeks until death or end of study. The primary efficacy endpoint was median progression-free survival (mPFS) for the second-line EVE treatment period; secondary endpoints included other survival measures, and safety evaluations were for second-line EVE and grade 3/4 toxicities attributable to PAZ and EVE. Results: Of 74 pts who started first-line PAZ, 38 received ≥1 dose of second-line EVE. The primary endpoint of mPFS from the start of second-line EVE and the secondary endpoint of mPFS with first-line PAZ (Table) were consistent with previous reports; no unexpected adverse events (AEs) were reported. All pts had ≥1 treatment-emergent AE, 83.8% had grade ≥3 AEs, and 71.6% had serious AEs. Of 34 total deaths, 29 were due to PD and 5 were due to AEs (2 related to EVE [lower respiratory tract infection; pulmonary sepsis]; 3 unrelated to study treatment). Conclusions: Efficacy and safety outcomes were consistent with published phase III data. The CATChEz study supports sequential first-line use of PAZ followed by EVE for the treatment of pts with advanced or metastatic RCC. Clinical trial information: NCT01545817. [Table: see text]

Chemotherapy plus radiotherapy (CT-RT) versus RT alone for patients with anaplastic oligodendroglioma: Long-term results of the RTOG 9402 phase III study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2008b-2008b ◽  
Author(s):  
J. Gregory Cairncross ◽  
Meihua Wang ◽  
Edward G. Shaw ◽  
Robert B. Jenkins ◽  
Bernd W. Scheithauer ◽  
...  
Keyword(s):  
Combined Therapy ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Long Term Results ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Entire Cohort ◽  
Phase Iii Study

2008b Background: Anaplastic oligodendrogliomas, pure (AO) and mixed (AOA), are chemosensitive tumors, especially if co-deleted for chromosomes 1p and 19q, but whether addition of CT to RT prolongs overall survival (OS), is unknown. Methods: In the RTOG 9402 Phase III trial, patients (pts) with AO/AOA were randomly assigned to PCV [procarbazine, CCNU (lomustine) and vincristine] followed by immediate RT vs. immediate RT alone. Early analysis showed no OS benefit for the PCV+RT group but combined therapy was associated with a longer progression-free survival (PFS). It also showed that the finding of 1p/19q co-deletion was associated with a longer OS independent of treatment. The current analysis has a median follow up of 11.3 years (yrs). Results: Two hundred ninety-one patients were randomized, 148 to PCV+RT and 143 to RT. PCV+RT was associated with longer PFS [2.5 vs. 1.7 yrs, hazard ratio (HR) 0.68, 95% confidence interval (CI) (0.53, 0.88), P = 0.003] and the 1p/19q co-deletion with a longer Median Survival Time (MST) [8.7 vs. 2.7 yrs, HR 0.41, 95% CI (0.30, 0.55), P < 0.001]. For the entire cohort, there was no difference in MST by treatment [4.6 yrs for PCV+RT vs. 4.7 yrs for RT, HR 0.79, 95% CI (0.60, 1.04), P = 0.1]. However, patients with 1p/19q co-deleted tumors lived much longer after PCV+RT (n = 59) than after RT (n = 67) [14.7 vs. 7.3 yrs, HR 0.59, 95% CI (0.37, 0.95), P = 0.03]. There was no difference in MST by treatment in pts without the 1p/19q co-deletion [n=137; 2.6 vs. 2.7 yrs, HR 0.85, 95% CI (0.58, 1.23), P = 0.39]. Re-operation rates upon progression were similar between treatment arms in co-deleted pts (43%, PCV+RT vs. 54%, RT) but salvage CT rates were higher in the RT arm [57% vs. 81% (P = 0.04)]. Conclusions: PCV followed by immediate RT was a highly effective therapy for patients with 1p/19q co-deleted AO/AOA. In this setting, 1p/19q co-deletion was both prognostic and predictive, and the early PFS benefit in co-deleted cases was a harbinger of their longer OS. [This work was supported by RTOG grants U10 CA21661 and U10 CA32115, NCCTG grant U10 CA25224, ECOG grants CA17145 and CA21115, SWOG grant CA32102, and CCOP grant U10 CA37422 from the National Cancer Institute (NCI)]

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