Patient-reported outcomes from POINTBREAK: The randomized, open-label, phase III study of pemetrexed (pem) + carboplatin (cb) + bevacizumab (bev) followed by maintenance pem + bev versus paclitaxel (pac) + cb + bev followed by maintenance bev in patients with stage IIIb or IV nonsquamous non-small cell lung cancer (NS-NSCLC).

2012 ◽  
Vol 30 (34_suppl) ◽  
pp. 53-53 ◽  
Author(s):  
David R. Spigel ◽  
Jyoti D. Patel ◽  
Craig H. Reynolds ◽  
Edward B. Garon ◽  
Robert C. Hermann ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Performance Status ◽  
Sensory Neuropathy ◽  
Well Being ◽  
Stage Iiib ◽  
Phase Iii ◽  
Open Label ◽  
Ecog Performance Status ◽  
Patient Reported ◽  
Grade 3

53 Background: Treatment (tx) impact on pt quality of life (QoL) informs pt and physician choices in the management of NSCLC. QoL, a secondary endpoint of POINTBREAK, was assessed using the patient-reported Functional Assessment of Cancer Therapy General (FACT-G), Lung (FACT-L), and Neurotoxicity (FACT&GOG-Ntx). Methods: Pts with previously untreated stage IIIB/IV NS-NSCLC and ECOG performance status 0-1 were randomized to receive induction Pem+Cb+Bev or Pac+Cb+Bev for up to 4 cycles. Pts without progressive disease received maintenance Pem+Bev (Pem Arm) or Bev (Pac Arm). Pts completed the FACT-G [physical, emotional, functional, and social well-being subscales (SS)], FACT-L (FACT-G + lung cancer SS), and FACT&GOG-Ntx (FACT-G + Ntx SS) at each visit. SS score and total score (TS) were calculated for each instrument. Tx group differences were analyzed using Linear Mixed Effects model. Toxicity was investigator assessed using CTCAE and was compared with Fisher’s exact test. Results: The primary endpoint of superior OS for the Pem arm was not met and is reported elsewhere. Pt overall compliance on the FACT was 91.2% (Pem Arm) and 90.0% (Pac Arm). For both the FACT-G and FACT-L TS, no overall significant change from baseline difference was observed between the Pem and Pac Arms. No overall differences were seen in SS scores except for Ntx. Pts on the Pem Arm had significantly less change from baseline in Ntx SS score and Ntx TS than pts in the Pac Arm at cycle 2 (p<0.001), and this significant tx effect persisted through induction and the six cycles of maintenance considered in the analysis. Significantly fewer pts on the Pem Arm experienced investigator assessed Grade 3/4 sensory neuropathy compared to the Pac Arm (0.0% vs. 4.1%, p<.00001). Conclusions: Based on the FACT results, pts on the Pem and Pac Arms reported similar changes in QoL except for less change from baseline in Ntx on the Pem Arm. Patient-reported Ntx is consistent with the clinically-measured drug-related Grade 3/4 sensory neuropathy.

A randomized comparison of carboplatin/vinorelbine versus carboplatin/gemcitabine in advanced non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7033-7033
Author(s):  
N. Helbekkmo ◽  
S. H. Sundtroem ◽  
U. Aaseboe ◽  
P. F. Brunsvig ◽  
C. L. Von Plessen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Performance Status ◽  
Stage Iiib ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Intention To Treat ◽  
Primary Endpoints ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
One Year

7033 Background: Carboplatin/vinorelbine (CV) and carboplatin/gemcitabine (CG) are novel 2-drug combinations in the treatment of NSCLC. In a randomized national multicenter phase III study in stage IIIB and IV patients (pts), we compared these regimens with respect to efficacy, toxicity and quality of life (QoL). Methods: Chemonaive pts with histologically or cytologically proven NSCLC, stage IIIB or IV and ECOG performance status (PS) 0–2 were eligible. There was no upper age limit. Pts received vinorelbine 25 mg/m2 or gemcitabine 1000 mg/m2, both administered on day 1 and 8, in combination with carboplatin (Chatelut AUC 4) at day 1. Three courses were administered in 3-week cycles. QoL questionnaires were completed at baseline, before each cycle and then every 8 weeks up to one year. Primary endpoints were survival and QoL and secondary endpoints toxicity and time to progression (TTP). Stratification was done for age, stage and PS, and the planned sample size per arm was minimum 200. The analyses were performed on an intention-to-treat basis Results: From Oct 2003 through Dec 2004, 433 pts from 33 institutions were randomized to CV (n=218) or CG (n=215). Follow-up was minimum one year. There was no difference in overall survival between the two arms (p=0.89). Median survival was 7.3 vs. 6.5 months and 1-year survival 28% and 31% in the CV and CG arm respectively. TTP was significantly longer in the CG arm (p=0.006) with median TTP 4.2 vs. 3.9 months. There was significantly more grade 3–4 anemia and thrombocytopenia in the CG arm (p<0.001) and more grade 3–4 leucopenia in the CV arm (p= 0.001). More pts in the CG arm needed transfusions of blood (p=0.003) or platelets (p=0.001). There was no difference between the arms with respect to neutropenic infections (p=0.87). QoL data are still being analyzed and will be presented at ASCO. Conclusions: Overall survival was similar in the two treatment arms. In the CG arm, the median TTP was longer, but grade 3–4 toxicity requiring interventions, was more frequent when compared to the VC arm. No significant financial relationships to disclose.

Exploratory analyses of efficacy and safety of pemetrexed (Pem) plus bevacizumab (Bev) and bev alone as maintenance therapy (MT) in patients (Pts) with stage IIIb or IV nonsquamous non-small cell lung cancer (NS-NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8012-8012
Author(s):  
Jyoti D. Patel ◽  
Edward B. Garon ◽  
Ramaswamy Govindan ◽  
Craig H. Reynolds ◽  
David R. Spigel ◽  
...  
Keyword(s):  
Survival Rates ◽  
Sensory Neuropathy ◽  
Median Number ◽  
Stage Iiib ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Open Label ◽  
Open Label Phase ◽  
The Difference ◽  
Grade 3

8012 Background: In a phase III superiority study, Pem+carboplatin (Cb)+Bev followed by Pem+Bev improved PFS compared with paclitaxel (Pac)+Cb+Bev followed by Bev in NS-NSCLC pts. Superior OS (primary endpoint) was not met. These analyses assessed the efficacy and safety in pts who received MT. Methods: Prespecified exploratory analyses were performed in the maintenance population (MP) and timed from the start of induction. Pts ≥18 years with stage IIIB/IV NS-NSCLC (ECOG status 0–1) from the multicenter, randomized, open-label, phase III superiority study were included in the MP if they received at least one dose of MT. For MT, pts received intravenous Pem 500 mg/m2+Bev 15 mg/kg (n=292) or Bev 15 mg/kg (n=298). OS, PFS, and safety were evaluated. Comparison is made to the intent-to-treat (ITT; Pem=472, Pac=467) or safety population (SP; Pem=442, Pac=443; received at least one dose of one drug). Results: Baseline pt and disease characteristics for the ITT and MP were similar between arms. In the ITT/MP population, the median number of cycles was 7/10 (range, 1-41/4–41) in the Pem arm and 6/9 (range, 1-39/5–39) in the Pac arm. In the ITT/MP, OS was 12.6/17.7 months (mos; Pem) and 13.4/15.7 mos (Pac). Survival rates (%) at 12 and 24 mos with Pem (ITT/MP) were 52.7/71.7 and 24.4/34.5; Pac, 54.1/66.5 and 21.2/26.5%. In pts not receiving MT, OS was 4.7 mos (Pem) and 6.1 mos (Pac). PFS (mos) in the ITT/MT was 6.0/8.6 (Pem) and 5.6/6.9 (Pac). In pts not receiving MT, PFS was 2.3 mos and 2.5 mos with Pem and Pac, respectively. From induction, both SP/MP had significantly more grade 3/4 thrombocytopenia, anemia, and fatigue with Pem and neutropenia and sensory neuropathy with Pac (p≤0.001). During MT only, the difference in grade 3/4 neutropenia rates between arms was no longer significant. Conclusions: Improved efficacy outcomes were consistent with previous Pem maintenance and Bev studies and no new toxicities were observed. Clinical trial information: NCT00762034.

Update results from ALTER-C-001: Efficacy and safety of anlotinib plus XELOX regimen as first-line treatment followed by maintenance monotherapy of anlotinib for patients with mCRC-A single-arm, multicenter, phase Ⅱ clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15550-e15550
Author(s):  
Jin Yan ◽  
Yunwei Han ◽  
Li Zhang ◽  
Yongdong Jin ◽  
Hao Sun
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Performance Status ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Open Label ◽  
Ecog Performance Status ◽  
Multicenter Phase ◽  
First Line Treatment

e15550 Background: The combination of anti-VEGF or anti-EGFR targeted drugs with chemotherapy is the standard first-line therapy for metastatic colorectal cancer (mCRC), and the followed maintenance treatment is an optional approach to balance the efficacy and toxicity. However, studies regarding the maintenance strategies based on antiangiogenic TKIs are limited currently. Anlotinib, a novel oral multi-target TKI which can inhibit both tumor angiogenesis and tumor cell proliferation simultaneously, substantially prolonged the PFS with manageable toxicity for refractory mCRC in the phase III ALTER0703 clinical trial. Here we report an update on the effectiveness and safety of anlotinib plus XELOX as first-line treatment followed by anlotinib monotherapy for mCRC. Methods: In this open label, single-arm, multicenter phase II clinical trial, 53 mCRC patients without prior systemic treated, aged 18-75 and an ECOG performance status of 0 or 1 were planned to recruit. Eligible patients received capecitabine (1000 mg/m2, po, d1-14, q3w) and oxaliplatin (130 mg/m2, iv, d1, q3w) plus anlotinib (10mg, po, d1̃14, q3w) treatment for 6 cycles. After 6 cycles of inducing therapy, patients would receive anlotinib (12mg, po, d1̃14, q3w) as maintenance therapy until disease progression or intolerable adverse events (AEs). The primary endpoint was PFS; Secondary endpoints included ORR, DCR, DOR and safety. Results: By the data analysis cutoff date of January 22, 2021, a total of 18 patients were enrolled, of which 12 patients were available for efficacy assessment. In best overall response assessment, there were 50.0% PR (6/12), 33.3% SD (4/12) and 16.7% PD (2/12). The ORR was 50.0% (95% CI, 21.1-78.9%) and DCR was 83.3% (95% CI, 51.5-97.9%). The longest duration of treatment was 8.8 months and the response was still ongoing. The median PFS was not reached. The most common treatment related adverse events (TRAEs) of any grade (≥20%) were leukopenia, hypertension, neutropenia, diarrhea, fatigue, hypertriglyceridemia. Grade 3/4 TRAEs included hypertension (22.2%), hypertriglyceridemia (11.1%), lipase elevated (11.1%) and neutropenia (5.6%). No grade 5 AEs occurred. Conclusions: The update results suggested that anlotinib combined with XELOX as first line regimen followed by anlotinib monotherapy showed promising anti-tumor activity and manageable safety for patients with mCRC. And the conclusions needed to be confirmed in trials continued subsequently. Clinical trial information: ChiCTR1900028417.

DREAMseq (Doublet, Randomized Evaluation in Advanced Melanoma Sequencing): A phase III trial—ECOG-ACRIN EA6134.

2021 ◽  
Vol 39 (36_suppl) ◽  
pp. 356154-356154
Author(s):  
Michael B. Atkins ◽  
Sandra J. Lee ◽  
Bartosz Chmielowski ◽  
Antoni Ribas ◽  
Ahmad A. Tarhini ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Initial Therapy ◽  
Phase Iii ◽  
Treatment Sequence ◽  
Ecog Performance Status ◽  
Randomized Evaluation ◽  
Alternate Therapy ◽  
Treatment Naïve ◽  
Grade 3

356154 Background: Combinations of immune checkpoint inhibitors (CPI) blocking PD-1 and CTLA-4 or BRAF/MEK inhibitors have both shown significant antitumor efficacy and overall survival (OS) benefit in patients (pts) with BRAFV600-mutant metastatic melanoma (MM), leading to broad regulatory approval. Little prospective data exists to guide the choice of one over the other as initial therapy or the preferred treatment sequence in this population. The DREAMseq Trial was designed to compare the efficacy and toxicity of the sequence of nivolumab/ipilimumab (N/I) followed by dabrafenib/trametinib (D/T) to the converse sequence. Methods: Eligible pts with treatment-naive BRAFV600-mutant MM were stratified by ECOG Performance Status (PS) 0 or 1 and LDH level and randomized 1:1 to receive Step 1 with either N/I (Arm A) or D/T (Arm B) and at disease progression (PD) were enrolled in Step 2 receiving the alternate therapy, D/T (Arm C) or N/I (Arm D), respectively. Pts received N (1mg/kg)/I (3 mg/kg) q3 wks x 4 doses followed by N 240 IV q2 wks for up to 72 wks (Arms A and D) or D 150 mg po BID and T 2 mg po qD until PD (Arms B and C). In 2019, investigators were given the option to use alternate induction dosing of N (3mg/kg)/I (1 mg/kg) q3 wks x 4 doses for Arms A and D. Cycles were every 6 wks and imaging was obtained at baseline and q12 wks on each arm. Primary endpoint was 2-year OS. At the 4th Interim Analysis with 59% of pts being 2 yrs from enrollment, the DSMC and NCI CTEP recommended halting accrual and releasing the data. Results: Beginning 7/2015, 265 out of a proposed 300 pts were enrolled (133 Arm A and 132 Arm B). Median age was 61 (25-85) and 63% were male. Demographics for Arm A and B were balanced with 67% PS 0 and 60% with normal LDH. As of 7/16/21, at a median follow-up of 27.7 mos, 27 pts had switched to Arm C and 46 to Arm D. Overall Grade 3+ toxicity was 60% in Arm A and 52% in Arm B. Grade 5 treatment-related AEs included 2 on Arm A and 1 on Arm C. ORR to date is: Arm A 46% (52/113), Arm B 43% (49/114), Arm C 48% (11/23) and Arm D 30% (8/27). 37/42 assessed pts in Arm A and 19/37 in Arm B remain in response. Median DOR: Arm A- Not reached; Arm B-12.7 mos (95% CI: 8.2, -) (p <0.001). There were 100 deaths (Arm A to C- 38/Arm B to D- 62). 2-yr OS rate for those starting with Arm A was 72% (95% CI: 62-81%) and for Arm B 52% (95% CI: 42-62%) (log-rank p= 0.0095). PFS showed a trend in favor of Arm A (log-rank p=0.054). Both the PFS and OS curves show a biphasic pattern with Arm B being above Arm A until 6 and 10 mos, respectively. For the 115 pts with documented progression on Step 1 (Arm A-44/Arm B-71), 60 (52%) had registered for Step 2. The principal reason for not enrolling on Step 2 was death from PD within 6 mos (Arm A:15/23; Arm B: 25/32). Conclusions: For pts with advanced BRAFV600-mutant MM, the treatment sequence beginning with the CPI combination of N/I resulted in superior OS, which became evident at 10 mos, with longer Step 1 DOR and more ongoing responses than the treatment sequence beginning with D/T. Clinical trial information: NCT02224781.

Predictors of early hospice or death in patients with inoperable lung cancer treated with curative intent.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20525-e20525
Author(s):  
Anna Mary Brown Laucis ◽  
Kimberly A. Hochstedler ◽  
Thomas Pence Boike ◽  
Benjamin Movsas ◽  
Craig William Stevens ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Logistic Regression ◽  
Predictive Model ◽  
Performance Status ◽  
Ecog Performance Status ◽  
Curative Intent ◽  
Heart Dose ◽  
Patient Reported ◽  
Mean Heart Dose ◽  
Nsclc Patients

e20525 Background: Treatment for inoperable stage II-III non-small cell lung cancer (NSCLC) involves aggressive chemo-radiotherapy (CRT). While outcomes have improved with immunotherapy, some patients transition to hospice or die early in their treatment course. To help identify these patients, we developed a predictive model for early poor outcomes in NSCLC patients treated with curative intent. Methods: In a statewide consortium involving 27 sites, information was collected prospectively on stage II-III NSCLC patients who received curative CRT from April 2012 to November 2019. We defined an early poor outcome as termination of treatment due to hospice enrollment or death within 5 months of initiating radiation therapy. Potential predictors included clinical characteristics and patient reported outcomes (PROs) from validated questionnaires. Logistic regression models were used to assess potential predictors and build predictive models. Multiple imputation was used to handle missing data. We used Lasso regularized logistic regression to build a predictive model with multiple predictor variables. Results: Of the total of 2267 included patients, 128 patients discontinued treatment early due to hospice enrollment or death. The mean age of the 128 patients was 71 years old (range 48-91) and 59% received concurrent chemotherapy. Significant uni-variable predictors of early hospice or death were advanced age, worse ECOG performance status, high PTV volume, short distance to normal tissue critical structures, high mean heart dose, uninsured status, lower scores on the Functional and Physical Well-Being scale and the Lung Cancer Symptoms sub-scale of the FACT-L quality of life instrument, as well as higher levels of patient-reported lack of energy, cough, and shortness of breath. The best predictive model included age, ECOG performance status, PTV volume, mean heart dose, patient insurance status, and patient-reported lack of energy and cough. The pooled estimate of area under the curve (AUC) for this multivariable model was 0.71, with a negative predictive value of 95%, specificity of 97%, positive predictive value of 23%, and sensitivity of 16% at a predicted risk threshold of 20%. Conclusions: Our models identified a combination of clinical variables and PROs that may help identify individuals with inoperable NSCLC undergoing curative intent chemo-radiotherapy who are at a high risk of early hospice enrollment or death. These preliminary results are encouraging and warrant further evaluation in a larger cohort of patients.

Open-Label, Multicenter, Randomized, Phase III Study Comparing Oral Topotecan/Cisplatin Versus Etoposide/Cisplatin As Treatment for Chemotherapy-Naive Patients With Extensive-Disease Small-Cell Lung Cancer

2006 ◽  
Vol 24 (13) ◽  
pp. 2044-2051 ◽  
Author(s):  
John R. Eckardt ◽  
Joachim von Pawel ◽  
Zsolt Papai ◽  
Antoaneta Tomova ◽  
Valentina Tzekova ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Open Label ◽  
Extensive Disease ◽  
Phase Iii Study ◽  
Grade 3 ◽  
Oral Topotecan

Purpose This open-label, randomized, multicenter phase III study compared oral topotecan/intravenous cisplatin (TC) with intravenous (IV) etoposide/cisplatin (PE) in patients with untreated extensive-disease small-cell lung cancer (ED-SCLC). Patients and Methods A total of 784 patients were randomly assigned to either oral topotecan 1.7 mg/m2/d × 5 with IV cisplatin 60 mg/m2 on day 5 (n = 389) or IV etoposide 100 mg/m2/d × 3 with IV cisplatin 80 mg/m2 on day 1 (n = 395) every 21 days. Results Overall survival (primary end point) was similar between groups (P = .48; median: TC, 39.3 weeks v PE, 40.3 weeks). One-year survival was 31% (95% CI, 27% to 36%) in both groups and the difference of −0.03 (95% CI, −6.53 to 6.47) met the predefined criteria of ≤ 10% absolute difference for noninferiority of TC relative to PE. Response rates were similar between groups (TC, 63% v PE, 69%). Time to progression was slightly but statistically longer with PE (log-rank P = .02; median: TC, 24.1 weeks v PE, 25.1 weeks). The regimens were similarly tolerable. Grade 3/4 neutropenia occurred more frequently with PE (84% v 59%), whereas grade 3/4 anemia and thrombocytopenia occurred more frequently with TC (38% v 21% and 38% v 23%, respectively). Lung Cancer Symptom Scale scores were statistically better with PE, but the differences were small and of debatable clinical significance. Conclusion Oral topotecan with cisplatin provides similar efficacy and tolerability to the standard (etoposide with cisplatin) in untreated ED-SCLC and may provide greater patient convenience compared with intravenous etoposide and cisplatin.

scholarly journals Phase III Randomized, Placebo-Controlled Trial of Docetaxel With or Without Gefitinib in Recurrent or Metastatic Head and Neck Cancer: An Eastern Cooperative Oncology Group Trial

2013 ◽  
Vol 31 (11) ◽  
pp. 1405-1414 ◽  
Author(s):  
Athanassios Argiris ◽  
Musie Ghebremichael ◽  
Jill Gilbert ◽  
Ju-Whei Lee ◽  
Kamakshi Sachidanandam ◽  
...  
Keyword(s):  
Head And Neck ◽  
Disease Progression ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Oncology Group ◽  
Ecog Performance Status ◽  
Grade 3

Purpose We hypothesized that the addition of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, to docetaxel would enhance therapeutic efficacy in squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods Patients with recurrent or metastatic SCCHN with Eastern Cooperative Oncology Group (ECOG) performance status of 2, or patients with ECOG performance status of 0 to 2 but were previously treated with chemotherapy, were randomly assigned to receive weekly docetaxel plus either placebo (arm A) or gefitinib 250 mg/d, orally (arm B) until disease progression. At the time of progression, patients in the placebo arm could receive single-agent gefitinib. EGFR, c-MET, and KRAS mutations and polymorphisms in drug metabolizing enzymes and transporters were evaluated by pyrosequencing. Results Two hundred seventy patients were enrolled before the study was closed early at interim analysis (arm A, n = 136; arm B, n = 134). Median overall survival was 6.0 months in arm A versus 7.3 months in arm B (hazard ratio, 0.93; 95% CI, 0.72 to 1.21; P = .60). An unplanned subset analysis showed that gefitinib improved survival in patients younger than 65 years (median 7.6 v 5.2 months; P = .04). Also, there was a trend for improved survival in patients with c-MET wild-type (5.7 v 3.6 months; P = .09) regardless of treatment. Grade 3/4 toxicities were comparable between the two arms except that grade 3/4 diarrhea was more common with docetaxel/gefitinib. Of 18 eligible patients who received gefitinib after disease progression in arm A, one patient had a partial response. Conclusion The addition of gefitinib to docetaxel was well tolerated but did not improve outcomes in poor prognosis but otherwise unselected patients with SCCHN.

E7389, a novel anti-tubulin, in patients with refractory breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 653-653 ◽  
Author(s):  
J. BlumL. Forero ◽  
M. K. Heiskala ◽  
N. Meneses ◽  
K. Chandrawansa ◽  
F. Fang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Performance Status ◽  
Safety Data ◽  
Synthetic Analog ◽  
Open Label ◽  
Ecog Performance Status ◽  
Group 2 ◽  
Grade 3 ◽  
Cycle Group ◽  
Group 1

653 Background: E7389 is a synthetic analog of halichondrin B, with a broad anti- proliferative activity against tumor cells. Methods: E7389 was evaluated in an open-label, single-arm Phase II trial as monotherapy for patients with refractory breast cancer (≥2 prior chemotherapy regimens, which must have included an anthracycline and a taxane). E7389 was administered as an IV bolus of 1.4 mg/m2 on Days 1, 8, and 15 of a 28-day cycle (group 1), or on Days 1 and 8 of a 21-day cycle (group 2). The primary efficacy endpoint was ORR. Results: As of 9 December 2005, 88 patients had received treatment, 68 in group 1 and 20 in group 2. Median age was 55 yrs (range 36–84) and ECOG performance status 0–1. Sixty-six percent of the tumors were ductal carcinomas, 6% lobular, and 27% were unclassified. Sixty percent of the tumors were ER+, 47% PR+, and 17% Her2/neu 3+. The patients had received at least two previous regimens, with a median number of 5 (range 2–14). Forty-eight percent of the patients had also used hormonal therapy. Forty-nine patients in group 1 and 12 patients in group 2 had completed their 2nd cycle of treatment, and twenty-one in group1 and 1 in group 2 their 4th cycle. Safety: The major toxicity related to study drug was neutropenia. Among 73 patients with preliminary safety data available, two patients had Grade 3 febrile neutropenia, and 31 had Grade 3 or 4 neutropenia or leukopenia. The other Grade 3 toxicities encountered in more than two patients were dehydration (4 patients) and dyspnea (4 patients). Grade 3 peripheral neuropathy was reported in 2 patients. Efficacy: At the end of cycle four there were 10 (15.2%) confirmed partial responses (PRs) out of 66 evaluable patients in group 1, and 1 confirmed PR (5.6%) out of 18 evaluable patients in group 2. The median duration of confirmed responses was 113 days. Conclusions: Based on the safety and efficacy in this refractory breast cancer population, E7389 appears to be a therapy worthy of continued investigation in patients with heavily pretreated breast cancer. In order to comply with the current demand for individualized cancer care, bio-markers which would predict the sensitivity to E7389 are being searched in the tumor samples of the patients in the current and forthcoming studies. [Table: see text]

Randomized phase II trial of carboplatin combined with weekly paclitaxel (CP) and docetaxel alone (D) in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC): NJLCG 0801.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7565-7565
Author(s):  
Shunichi Sugawara ◽  
Makoto Maemondo ◽  
Toshiyuki Harada ◽  
Akira Inoue ◽  
Nobumichi Matsubara ◽  
...  
Keyword(s):  
Performance Status ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Toxicity Profile ◽  
Ecog Performance Status ◽  
Loss To Follow Up ◽  
Lethal Arrhythmia ◽  
Grade 3

7565 Background: Standard first-line chemotherapy for elderly NSCLC pts has been considered as a monotherapy with vinorelbine or gemcitabine globally. However, we have demonstrated the high efficacy of CP for elderly pts in our previous trial (Ann Oncol 2010). Meanwhile, D has been considered as an alternative option for this population in Japan according to the result of WJTOG9904 (JCO 2006). Thus we compared the two regimens to select the proper candidate for future phase III trial. Methods: Eligible pts were aged 70 years or older with newly diagnosed stage IIIB/IV NSCLC; ECOG performance status 0-1; adequate organ function; written informed consent. Pts were randomized to receive carboplatin (AUC 6) on day 1 and paclitaxel (70mg/m2 on day 1, 8, and 15) every 4 weeks or D (60mg/m2 on day 1) every 3 weeks. The primary endpoint was overall response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival, and toxicity profile. Assuming that ORR of 40% would be potential usefulness while ORR of 20% would be the lower limit of interest, 40 pts in each arm were required if expect 10% loss to follow up. Results: Between July 2006 and September 2010, 84 pts were enrolled and 41 pts in CP arm and 42 pts in D arm were eligible (median age, 76 years; 75% male; 72% stage IV). Median treatment cycle was 4 in each arm (CP, range 1-6; D, range 1-8). ORRs were 51% (95%CI: 36-66%) and 26% (95%CI: 12-39%) in the CP and D arm, respectively. With a median follow-up of 18.4 months, median PFS were 6.5 and 3.9 months in the CP and D arm, respectively (Logrank, P=0.0027). Grade 3 or severer toxicities were as follows: neutropenia (CP, 56% and D, 79%), anemia (CP, 15% and D, 7%), thrombocytopenia (CP, 10% and D, 0%), infection (CP, 20% and D, 25%). One treatment-related death due to neutropenia, pneumonia, and lethal arrhythmia occurred in D arm but none in CP arm. Conclusions: The platinum doublet CP achieved higher activity with an acceptable toxicity profile for elderly pts with advanced NSCLC compared to monotherapy with D. The superiority of CP to the monotherapy in this trial is consistent with results of recent IFCT-0501 trial (Lancet 2011).

Randomized phase III trial of regorafenib in patients (pts) with metastatic and/or unresectable gastrointestinal stromal tumor (GIST) progressing despite prior treatment with at least imatinib (IM) and sunitinib (SU): GRID trial.

2012 ◽  
Vol 30 (18_suppl) ◽  
pp. LBA10008-LBA10008 ◽  
Author(s):  
George D. Demetri ◽  
Peter Reichardt ◽  
Yoon-Koo Kang ◽  
Jean-Yves Blay ◽  
Heikki Joensuu ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Controlled Trial ◽  
Performance Status ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Double Blind Study ◽  
Open Label ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Multikinase Inhibitor

LBA10008 Background: Oral multikinase inhibitor regorafenib (REG) demonstrated substantial activity in a phase II trial in pts with GIST after failure of both IM and SU (J Clin Oncol. 2011; 29:606s; abstr 10007). This phase III, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of REG for this unmet clinical need. Methods: Eligible pts had metastatic and/or unresectable GIST, objective failure of both prior IM and SU (progressive disease [PD] on, or intolerance to, IM and PD on SU), ≥1 measurable lesion, ECOG performance status 0 or 1. Pts were randomized 2:1 to receive best supportive care plus either REG 160 mg po once daily (3 wks on/1 wk off) or placebo (PL). The primary endpoint was progression-free survival (PFS) (modified RECIST 1.1, independent central review). Secondary endpoints included overall survival (OS), disease control rate (DCR, defined as rate of partial response [PR] plus stable disease [SD] lasting for ≥12 wks), response rate and duration, safety and correlative genotype analyses. At time of PD, pts were eligible for unblinding and crossover to open-label REG. Results: Between Jan and Aug of 2011, 234 pts were screened; 199 were randomized (REG: 133, PL: 66). Pts were stratified at randomization according to number of prior systemic therapies and geographical region. Baseline characteristics were balanced between the two arms. The primary endpoint was met: median PFS was 4.8 months for REG vs. 0.9 months for PL. Hazard ratio for PFS was 0.27 (95% CI, 0.18-0.39), p<0.0001. PFS rates at 3 and 6 months were 60% and 38% for REG vs. 11% and 0% for PL. DCR was 53% (REG) vs. 9% (PL).The HR for OS was 0.77 (p=0.20) with 85% PL pts having crossed over to REG. The most common > grade 3 treatment-emergent AEs in the REG arm during double-blind study were hypertension (28%), hand-foot skin reaction (21%), and diarrhea (8%). Conclusions: This randomized trial demonstrated that REG significantly improved PFS and DCR in pts with advanced GIST after failure of at least prior IM and SU. REG was well tolerated, with AEs as expected for this class and manageable with dose modifications.

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