Toxicity of epirubicin and cyclophosphamide (EC) vs. docetaxel (D) followed by EC in the adjuvant (adj) treatment of node positive breast cancer. A multicenter randomized phase III study (GOIM9902)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10526-10526
Author(s):  
M. Lopez ◽  
M. Brandi ◽  
P. Foggi ◽  
F. Giotta ◽  
N. Gebbia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cardiac Toxicity ◽  
Phase Iii ◽  
Cross Resistance ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Sequential Trials ◽  
To Receive ◽  
Hormonal Receptor Status ◽  
Normal Cardiac Function

10526 Background: Due to high activity of taxanes (T) and anthracyclines (A) in advanced breast cancer (BC) and to the lack of cross-resistance between them, several adjuvant (adj) trials have been performed to test the efficacy of combination or sequential schedules of T and A adjuvant. In most of the sequential trials A followed T. The sequence T->A was proven active in metastatic BC, but no data are available in the adj setting. This multicenter randomized phase III study was designed to evaluate the efficacy of the sequence T->A vs an A containing regimen Methods: Pts with pT1–3 pN1 M0 (UICC1997) BC, age 18–70, PS(ECOG) 0–1, normal cardiac function, adequate bone marrow, hepatic and renal function were eligible for the study. Pts were stratified according to institution, age (≤ 50 vs > 50), hormonal receptor status and number of involved nodes (≤ 3, 4–9, ≥ 10) and were randomized to receive either 4 cycles of EC (Epirubicin 120 mg/m2 + Cyclophosphamide 600 mg/m2 on day 1 q21) in arm A or 4 cycles of D (100 mg/m2 on day 1 q21) followed by 4 cycles of EC in arm B. Primary endpoint was DFS. Secondary endpoints OS and toxicity. Results: Between april 1999 and october 2005, 750 pts were enrolled (374 in arm A and 376 in arm B) in 25 Italian institutions. Pts characteristics are as follows: Arm A: age ≤ 50 yrs 185/374; ≤ 3 nodes 182/374, 4–9 nodes 129/374, ≥ 10 nodes 63/374; positive HR 287/374 Arm B: age ≤ 50 yrs 197/376; ≤ 3 nodes 184/376, 4–9 nodes 131/376, ≥ 10 nodes 61/376; positive HR 289/376 Toxicity data (Arm A vs Arm B) of the first 495(241/254) pts are the following: Neutropenia G3 (29% vs 21.3%), neutropenia G4 (32.7% vs 48.8%), febrile neutropenia G3–4 (3.7% vs 9.5%), thrombocytopenia G3–4 (3.3% vs 1.6%), anemia G3 (0% vs 2.4%), N/V G3–4 (6.2% vs 3.1%), mucositis G3–4 (3.7% vs 3.9%), diarrhea G3–4 (0.4% vs 2.8%), peripheral neuropathy G1–3 (0% vs 9.9%), hypersensitivity reactions G3–4 (0% vs 4.3%), cardiac toxicity G3 (0.4% vs 0%) Conclusions: Treatment was generally well tollerated in both arms with a higher incidence of neutropenia, usually short lasting, in arm B. The use of prophylactic G-CSF in those patients experiencing neutropenia G3–4 may be advisable. There were no significant differences in cardiac toxicity. No significant financial relationships to disclose.

A phase III study comparing amrubicin and cisplatin (AP) with irinotecan and cisplatin (IP) for the treatment of extended-stage small cell lung cancer (ED-SCLC): JCOG0509.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7003-7003 ◽  
Author(s):  
Yoshikazu Kotani ◽  
Miyako Satouchi ◽  
Masahiko Ando ◽  
Kazuhiko Nakagawa ◽  
Nobuyuki Yamamoto ◽  
...  
Keyword(s):  
Standard Treatment ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Severe Diarrhea ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Ecog Ps ◽  
To Receive

7003 Background: IP is the standard treatment for ED-SCLC, however often cause severe diarrhea. AP have shown promising activity in SCLC with fewer diarrhea. We conducted a phase III trial comparing AP with IP. Methods: Eligibility criteria included patients (pts) with chemotherapy-naïve, ED-SCLC, aged 20 to 70, and ECOG PS 0-1. Pts were randomized to receive either IP or AP, balancing for site, sex, and PS. IP comprised administration of I (60 mg/m2) iv on days 1, 8, and 15, and P (60 mg/m2) iv on day1,every 4 weeks. AP comprised administration of A (40 mg/m2) iv on day 1-3, and P (60 mg/m2) iv on day1, every 3 weeks. The planned sample size was 141 pts in each arm with a one-sided alpha of 5% and power of 70% and a non-inferiority margin of hazard ratio (HR) as 1.31. The primary endpoint was overall survival (OS). The secondary endpoints were response rate (RR), progression-free survival (PFS), adverse events (AEs), and quality of life (QOL). We evaluated pts’ QOL twice: at the baseline and after completion of the second course. Results: 284 pts were randomized to IP (n=142) and AP (n=142). Median age was 63, 84% were male, and 56% had PS 0. When 191pts enrolled, more febrile neutropenia (FN) was observed in AP than anticipated, and the initial dose of A was decreased from 40 mg/m2 to 35 mg/m2. At the second interim analysis conducted after the completion of patient accrual, the median OS of AP (15.0 m) was much worse than that of IP (18.3 m) and the HR (1.41; 96.3% CI, 1.03-1.93) exceeds even the non-inferiority margin, so the Data and Safety Monitoring Committee recommended early publication of the results. Median PFS was 5.7 (IP) vs. 5.2 months (AP) (HR 1.43, 95% CI, 1.13-1.82). RR was 69.5% (IP) vs. 77.9% (AP) (p=0.14). AEs in IP and AP arm were Grade 4 neutropenia (22.5% vs. 78.6%), G3-4 FN (10.7% vs. 32.1%), and G3-4 diarrhea (7.1% vs.1.4%). Proportion of improvement in physical status of QOL was 37.1%(IP) vs. 31.7%(AP), (odds ratio 0.72; 95%CI, 0.43-1.22; P=0.227). Conclusions: AP showed more bone marrow suppression than expected although it caused less diarrhea. The non-inferiority of AP to IP was not demonstrated and IP remains the standard treatment for ED-SCLC.

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.

Preemptive versus deferred lamivudine in preventing chemotherapy (CT) interruptions in hepatitis B (HBV) carriers with non-hematological malignancy—preliminary report of a randomized phase III study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. LBA19684-LBA19684
Author(s):  
R. K. Ngan ◽  
H. Y. Yiu ◽  
H. C. Cheng ◽  
C. K. Kwan ◽  
T. W. Lam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hematological Malignancy ◽  
Dose Intensity ◽  
Normal Liver ◽  
Drug Dose ◽  
Viral Reactivation ◽  
Phase Iii ◽  
Hbv Reactivation ◽  
Phase Iii Study ◽  
To Receive

LBA19684 Background: About 10% cancer patients (pts) are HBV carriers in endemic areas, who have a risk of HBV reactivation with CT preventable by Lamivudine (Lam). Methods: Pts seropositive for HBV surface antigen (HBsAg+) planned to receive ≥ 4 cycles of CT for non-hematological malignancy were randomized to receiving either preemptive Lam during and for 8 weeks after CT (arm I), or observation only and deferred Lam at biochemical hepatitis reactivation (arm II). All pts had normal liver enzymes & clotting profiles, age 18–75 & KPS >50 before entry. Serial clotting profile, liver enzyme and HBV DNA levels were monitored during CT and for 15 weeks post-CT. The endpoints include % of CT interruptions due to HBV reactivation (primary), HBV reactivation %, CT drug dose intensity levels & HBV reactivation-free survival (all secondary). 110 pts are estimated to give a power of 90% to detect the projected difference in the primary endpoint at 2-sided alpha error of 0.05. Results: Pt accrual was completed in 1/07. As at 3/07, 92 (81%) of the 114 pts randomized have completed the study or died, and were included for analysis. Breast & lung cancer constituted 71% of the cancers. There was no statistical difference in pt, cancer, CT, or viral characteristics between the 2 arms. Results are summarized in table . All 4 pts with CT interruptions and 11/14 pts with HBV reactivation had breast cancer. No difference in CT drug dose intensity levels was observed. Steroid used in the anti-emetic regimen was a significant factor in predicting viral reactivation in arm II pts in multivariate analysis. Conclusions: Although the incidence of CT interruptions was low in unselected pts without preemptive Lam, it was much higher in breast cancer pts despite deferred Lam, who also had significant rates of biochemical hepatitis & viral reactivation. Preemptive Lam should be given to breast cancer pts, & considered in other cancer pts receiving CT who are HBsAg+. [Table: see text] No significant financial relationships to disclose.

Efficacy and safety of BCD-017, a novel pegylated filgrastim: Results of open-label controlled phase II study in patients with breast cancer receiving myelosuppressive chemotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20593-e20593 ◽  
Author(s):  
Olga V. Salafet ◽  
Tatiana V. Chernovskaya ◽  
Ludmila P. Sheveleva ◽  
Andrey V. Khorinko ◽  
Tatiana I. Prokopenko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Iii ◽  
Severe Neutropenia ◽  
Comparable Efficacy ◽  
Efficacy And Safety ◽  
Open Label ◽  
Group A ◽  
Phase Iii Study ◽  
Study Support ◽  
To Receive

e20593 Background: Pegfilgrastim (conjugate of filgrastim and 20 kDa polyethylene glycol (PEG) is approved for treatment of chemotherapy-associated neutropenia. BCD-017 (empegfilgrastim) is a covalent conjugate of filgrastim with 30 kDa PEG. Increased molecular weight of PEG molecule may provide additional benefits compared to pegfilgrastim. Methods: To compare efficacy and safety of filgrastim and BCD-017 at 3 mg and 6 mg doses an open-label, randomized, active-comparator, non-inferiority trial was conducted. 60 patients with histologically or cytologically confirmed breast cancer were randomly assigned to receive either subcutaneous (s.c.) injection of 3 mg BCD-017 (n=21), 6 mg BCD-017 (n = 20), or 5 mg/kg s.c. injections of filgrastim (n=19) administered daily until ANC ≥ 10x109 cells/L (maximum of 14 days) after chemotherapy (doxorubicin 60 mg/m2 and docetaxel 75 mg/m2) with stratification for weight and prior chemotherapy exposure. The primary efficacy endpoint was the incidence of severe neutropenia (ANC < 1.0x109 cells/L) during the first cycle of chemotherapy. Results: Incidence of severe neutropenia during the first chemotherapy cycle was 85,7%, 65,0% and 61,1% in BCD-017 3 mg, BCD-017 6 mg and filgrastim groups, respectively. Differences between BCD-017 groups and filgrastim group were not significant. Mean duration of grade 4 neutropenia in cycle 1 was 0,43, 0,40 and 0,33 days, accordingly (95% CI for difference between BCD-017 3 mg and filgrastim groups -0.22 to 0.41; 95% CI for difference between BCD-017 6 mg and filgrastim groups -0.25 to 0.38). Febrile neutropenia was observed only in BCD-017 3 mg and BCD-017 6 mg groups (one case in each group). A single administration of BCD-017 at the doses of 3 mg and 6 mg was as safe and well tolerated as standard daily filgrastim administration. There were no unexpected adverse events in all groups. Conclusions: The results of this study support comparable efficacy of single s.c. injection of 6 mg BCD-017 versus daily 5 mg/kg s.c. injections of filgrastim. Further phase III study of BCD-017 for treatment and prophylaxis of neutropenia in patients receiving chemotherapy is necessary. Clinical trial information: NCT01569087.

IMmotion151: A Randomized Phase III Study of Atezolizumab Plus Bevacizumab vs Sunitinib in Untreated Metastatic Renal Cell Carcinoma (mRCC)

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 578-578 ◽  
Author(s):  
Robert J. Motzer ◽  
Thomas Powles ◽  
Michael B. Atkins ◽  
Bernard Escudier ◽  
David F. McDermott ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Anti Vegf ◽  
Treatment Naïve ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Intent To Treat ◽  
The Individual ◽  
To Receive

578 Background: Atezolizumab (atezo; anti–PD-L1) + bevacizumab (bev; anti-VEGF) showed first-line (1L) anti-tumor activity with a manageable safety profile in PD-L1+ mRCC pts in a Phase II study (McDermott ASCO-GU 2017). Here we describe the first randomized Phase III trial of a PD-L1/PD-1 pathway inhibitor combined with an anti-VEGF agent in 1L mRCC. Methods: IMmotion151 (NCT02420821) enrolled treatment-naïve pts regardless of prognostic risk group randomized 1:1 to receive atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w or sunitinib (sun) 50 mg PO QD 4 wk on/2 wk off. Pts were stratified by PD-L1 status (< 1% vs ≥ 1% PD-L1 expression on tumor-infiltrating immune cells [IC]; SP142 IHC assay). Coprimary endpoints: progression-free survival (PFS; by investigator per RECIST v1.1) in PD-L1+ pts (≥ 1% IC) and overall survival (OS) in intent-to-treat (ITT) pts. Secondary endpoints included PFS in ITT pts, ORR and DOR. Results: Baseline characteristics were comparable between arms within PD-L1+ (40% of ITT) and ITT pts. Median survival follow-up was 15 mo. PFS HR for atezo + bev vs sun was 0.74 (95% CI 0.57, 0.96) in PD-L1+ pts and 0.83 (95% CI 0.70, 0.97) in ITT pts. OS was immature at first interim analysis. PFS benefit was consistent across analyzed subgroups, including MSKCC risk, liver metastases and sarcomatoid histology. In PD-L1+ pts, ORR was 43% and DOR was not reached for atezo + bev vs 35% and 12.9 mo for sun. 40% of atezo + bev–treated pts and 54% of sun-treated pts had treatment-related Gr 3-4 AEs; 12% and 8% of treatment-related all-Gr AEs led to discontinuation, respectively. Conclusions: The study showed longer PFS for atezo + bev vs sun in PD-L1+ pts. Improved PFS was also observed in ITT pts. Safety was consistent with that of the individual agents. These results support the use of atezo + bev as a 1L treatment option in mRCC. Clinical trial information: NCT02420821. [Table: see text]

Adjuvant trial of 12 cycles of CMFPT followed by observation or continuous tamoxifen versus four cycles of CMFPT in postmenopausal women with breast cancer: an Eastern Cooperative Oncology Group phase III study.

1990 ◽  
Vol 8 (4) ◽  
pp. 599-607 ◽  
Author(s):  
H C Falkson ◽  
R Gray ◽  
W H Wolberg ◽  
K W Gillchrist ◽  
J E Harris ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Oncology Group ◽  
Life Threatening ◽  
Phase Iii Study ◽  
Time To Relapse ◽  
To Receive

A prospectively controlled randomized trial to compare the adjuvant efficacy of 12 cycles of cyclophosphamide, methotrexate, fluorouracil, prednisone, and tamoxifen (CMFPT) followed by observation or a total of 5 years of continuous tamoxifen versus four cycles of CMFPT followed by observation in postmenopausal women with operable node-positive breast cancer was started by the Eastern Cooperative Oncology Group (ECOG) in 1982. In 1986 the study was modified to allow patients on CMFPT X 12 plus continuous tamoxifen to be rerandomized after completing 5 years of tamoxifen to either continue for life or to stop therapy. Patients were stratified for number of involved nodes and estrogen-receptor (ER) status and randomized to receive one of three treatments: CMFPT X 4, CMFPT X 12, or CMFPT X 12 plus continuous tamoxifen. Of 962 patients entered on the study, 803 were eligible. Life-threatening toxicity occurred in 75 and lethal toxicity in seven patients. Median follow-up is 4.1 years; 279 patients had recurrent disease. Time to relapse (TTR) is significantly longer for patients on CMFPT X 12 plus continuous tamoxifen than for CMFPT X 4 (P = .002), or CMFPT X 12 (P = 0.05). Differences between four or 12 cycles of CMFPT are not significant; relapse-free rates at 5 years are 61% for CMFPT X 12 plus continuous tamoxifen, 51% on CMFPT X 12, and 52% on CMFPT X 4. Treatment differences in overall survival are not significant. Hormone receptor status and number of involved nodes were found to be significant prognostic parameters.

Double-blind, randomized phase III study to compare the efficacy and safety of CT-P6, trastuzumab biosimilar candidate versus trastuzumab as neoadjuvant treatment in HER2 positive early breast cancer (EBC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 510-510 ◽  
Author(s):  
Justin Stebbing ◽  
Yauheni Valerievich Baranau ◽  
Valery Baryash ◽  
Alexey Manikhas ◽  
Vladimir Moiseyenko ◽  
...  
Keyword(s):  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Her2 Positive ◽  
Double Blind ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
To Receive ◽  
Related Reaction

510 Background: CT-P6 (C) is a proposed biosimilar to trastuzumab. This trial (NCT02162667) evaluated the similarity of C and trastuzumab in efficacy and safety for HER2+ EBC. Methods: 549 patients with HER2+ EBC were randomized to receive C (n=271) or trastuzumab (n=278) in combination with docetaxel (Cycles 1-4) and 5-fluorouracil, epirubicin, and cyclophosphamide (Cycles 5-8). C or trastuzumab was administered at 8 mg/kg (Cycle 1 only) followed by 6 mg/kg every 3 weeks. The primary endpoint was pathological complete response (pCR) rate at surgery. Secondary endpoints were overall response rate (ORR), PK, PD and safety. After surgery, patients received adjuvant C or trastuzumab to complete a total of 1-year treatment. Results: The pCR rate was 46.8% for C and 50.4% for trastuzumab. The 95% CIs for the risk ratio estimate were within the equivalence margin (0.74, 1.35) in PPS and ITT analyses. Other efficacy endpoints were similar between C and trastuzumab. The proportion of patients with at least 1 treatment-emergent SAE was 6.6% for C and 7.6% for trastuzumab. Only 1 patient in each group withdrew treatment due to significant LVEF decrease. Infusion-related reaction was reported for 8.5% of patients in C and 9.0% of patients in trastuzumab. Conclusions: This study demonstrated the similarity of efficacy in terms of pCR between CT-P6 and trastuzumab in EBC patients. Secondary efficacy endpoints also supported the similarity between CT-P6 and trastuzumab. CT-P6 was well tolerated with a similar safety profile to that of trastuzumab during the neoadjuvant period. Clinical trial information: NCT02162667. [Table: see text]

METRIC phase III study: Efficacy of trametinib (T), a potent and selective MEK inhibitor (MEKi), in progression-free survival (PFS) and overall survival (OS), compared with chemotherapy (C) in patients (pts) with BRAFV600E/K mutant advanced or metastatic melanoma (MM).

2012 ◽  
Vol 30 (18_suppl) ◽  
pp. LBA8509-LBA8509 ◽  
Author(s):  
Caroline Robert ◽  
Keith T. Flaherty ◽  
Peter Hersey ◽  
Paul D. Nathan ◽  
Claus Garbe ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Mek Inhibitor ◽  
Phase Iii ◽  
Rank Test ◽  
Brafv600e Mutation ◽  
Independent Review ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Grade 3 ◽  
To Receive

LBA8509 Background: Dacarbazine (D) and paclitaxel (P) have been used to treat MM pts with limited effect. The MM treatment landscape has recently changed with the approval of vemurafenib and ipilimumab in 2011, but secondary malignancies or other toxicities are of concerns. T is a reversible, highly selective allosteric inhibitor of MEK1/2 activation and kinase activity. In a PhII trial (NCT01037127), pts with BRAFV600E mutation MM had median PFS of 5.3 mos. This PhIII trial (NCT01245062) was conducted in pts with BRAFV600E/K mutant advanced or MM. Methods: Pts were randomized 2:1 to T (2mg QD) or C (D or P). Pts were stratified by baseline LDH level and prior C; pts in the C arm were allowed to crossover to receive T after confirmation of PD. Primary endpoint was PFS in pts with BRAFV600E mutation-positive MM and no prior brain mets; secondary endpoints were OS, ORR and safety in primary and ITT. PFS and OS were compared using a stratified log-rank test. The study was designed with ≥99% power and one-sided α = 0.025 to detect 57% reduction in the risk of PD or death in pts treated with T vs C. Results: Between Dec 2010 and Jul 2011, 322 pts were randomized to T (n=214) or C (n=108); 273 pts were BRAFV600E mutation-positive with no prior brain mets. HR for primary population for PFS by investigator was 0.44 (95% CI 0.31–0.64; p<0.0001) in favor of T with a median PFS of 4.8 mo vs 1.4 mo with C. PFS benefit in favor of T was observed in ITT; this was confirmed by an independent review. The confirmed ORR was 24% with T and 7% with C. HR for interim OS was 0.53 (95% CI 0.30–0.94; p=0.0181), in favor of T in primary population. OS benefit was consistent in ITT pop despite 51 pts crossover from C to T. The most frequent AEs with T were skin rash, diarrhea, edema, hypertension, fatigue. Known MEKi class effects were observed, e.g. chorioretinopathy (<1%) and decreased ejection fraction (7%). Grade 3 AEs in T arm were hypertenstion (12%) and rash (7%). Conclusions: T is the first in class MEKi associated with a significant improvement of PFS and OS compared to C in pts with BRAFV600E/K mutant MM.

Pegylated Liposomal Doxorubicin Plus Docetaxel Significantly Improves Time to Progression Without Additive Cardiotoxicity Compared With Docetaxel Monotherapy in Patients With Advanced Breast Cancer Previously Treated With Neoadjuvant-Adjuvant Anthracycline Therapy: Results From a Randomized Phase III Study

2009 ◽  
Vol 27 (27) ◽  
pp. 4522-4529 ◽  
Author(s):  
Joseph A. Sparano ◽  
Anatoly N. Makhson ◽  
Vladimir F. Semiglazov ◽  
Sergei A. Tjulandin ◽  
Olga I. Balashova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Disease Progression ◽  
Liposomal Doxorubicin ◽  
Cardiac Toxicity ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
Time To Progression ◽  
Anthracycline Therapy ◽  
Phase Iii Study

PurposeTo determine whether the combination of pegylated liposomal doxorubicin (PLD) and docetaxel significantly prolongs time to disease progression compared with docetaxel alone without an increase in cardiac toxicity in women with advanced breast cancer who had experienced relapse at least 1 year after prior adjuvant or neoadjuvant anthracycline therapy.Patients and MethodsThis international, phase III study randomly assigned 751 patients to receive either docetaxel 75 mg/m2(n = 373) or PLD 30 mg/m2followed by docetaxel 60 mg/m2every 21 days (n = 378) and continued until disease progression or prohibitive toxicity. The primary end point was time to progression (TTP). Secondary end points were overall survival (OS), objective response rate (ORR), cardiac toxicity, and safety.ResultsTreatment with PLD-docetaxel significantly improved median TTP from 7.0 to 9.8 months (hazard ratio [HR] = 0.65; 95% CI, 0.55 to 0.77; P = .000001) and the ORR from 26% to 35% (P = .0085). OS was similar between the two groups (HR = 1.02; 95% CI, 0.86 to 1.22). The incidence of grade 3 or 4 adverse events were similar (78% v 72%), although a higher incidence of hand-foot syndrome (24% v 0%) and mucositis/stomatitis (12% v 1%) were observed in the PLD-docetaxel combination. Protocol-defined left ventricular ejection fraction decreases and congestive heart failure were reported in 5% and 1% in both treatment arms, respectively.ConclusionThe PLD-docetaxel combination was more effective than docetaxel alone in women with metastatic breast cancer who had experienced relapse at least 1 year after prior adjuvant anthracycline therapy without an increase in cardiac toxicity, although mucocutaneous toxicity was more common.

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