Final analysis of nelipepimut-S plus GM-CSF with trastuzumab versus trastuzumab alone to prevent recurrences in high-risk, HER2 low-expressing breast cancer: A prospective, randomized, blinded, multicenter phase IIb trial.

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 1-1 ◽  
Author(s):  
Annelies Hickerson ◽  
G. Travis Clifton ◽  
Diane F. Hale ◽  
Kaitlin M. Peace ◽  
Jarrod P. Holmes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Interim Analysis ◽  
Prolonged Exposure ◽  
Early Stage ◽  
Final Analysis ◽  
Control Group ◽  
Gm Csf ◽  
Disease Free ◽  
Clinical Trial Information

1 Background: Preclinical data shows synergism between trastuzumab (Tz) and HER2-targeted vaccines. We evaluated adjvuant nelipepimut-S (NPS) + GM-CSF with Tz compared to Tz with GM-CSF alone in HER2 low-expressing (LE) breast cancer (BC) patients (pts) to prevent recurrences. After a planned interim analysis showed benefit in triple negative BC (TNBC) pts, the decision was made to close the trial with guidance from the independent DSMB. Here, we report the final analysis of the trial with 7 months (mo) of added follow-up (f/u). Methods: The phase 2b trial enrolled clinically disease-free BC pts after standard therapy. Pts were HLA-A2, A3, A24, and/or A26+, had HER2-LE (IHC 1-2+, FISH non-amplified) BC and were node positive and/or TNBC. Pts were randomized to placebo with GM-CSF(control group, CG) or NPS with GM-CSF (vaccine group, VG), while all received Tz Q3wk for 1 year. GM-CSF or NPS + GM-CSF were given q3wks x 6 starting with the 3rd Tz dose, and boosters every 6 months x 4. Safety was assessed and pts were followed clinically for recurrences. The primary outcome was DFS at 24 mo. Results: 589 pts were screened at 26 sites. 275 pts were enrolled and randomized (VG:136, CG:139). There were no clinicopathologic differences between groups. Concurrent Tz and NPS was safe with no added overall or cardiac toxicity compared to CG and no grade 4/5 toxicities. In the ITT analysis (median f/u 25.7 mo), the estimated DFS was favorable but did not reach significance in the VG compared with the CG (HR 0.62, 95% CI: 0.31-1.25, p = 0.18). In the TNBC pts, the VG had statistically improved DFS compared to the CG (HR 0.26, 95% CI: 0.08-0.81, p = 0.013). Conclusions: The combination of NPS with Tz is safe with no added toxicity compared to Tz alone, even after prolonged exposure (25.7 mo). In this final analysis, there was a trend towards benefit in the ITT population that improved since the interim analysis with added f/u. The significant benefit seen at interim in the TNBC pts continued to strengthen in the VG group. These findings could position the NPS + Tz combination as an adjuvant therapy for early-stage TNBC and warrant further study. Clinical trial information: NCT01570036.

Early efficacy analysis of the AE37 vaccine in patients with HER2 low-expressing and triple-negative breast cancer.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 109-109 ◽  
Author(s):  
Elizabeth Ann Mittendorf ◽  
Sonia A. Perez ◽  
Diane F. Hale ◽  
Timothy J. Vreeland ◽  
Alan K. Sears ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Reduction ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Phase Iii ◽  
Control Group ◽  
Her2 Expression ◽  
Gm Csf ◽  
Helper Epitope ◽  
Disease Free

109 Background: Peptide vaccines comprised of HLA class II epitopes, which elicit CD4+ T cell responses, play a critical role in potentiating immune responses. We are conducting a randomized phase II trial of AE37, a hybrid peptide created by the addition of the Ii-Key moiety (LRMK) to the HER2 helper epitope, AE36 (HER2 aa776-790). Here, we present efficacy data focusing on outcomes in patients with low HER2 (IHC 1+ or 2+) expression and triple negative breast cancer (TNBC). Methods: The trial is enrolling node positive or high risk node negative breast cancer patients with any degree of HER2 expression (IHC 1+, 2+ or 3+ or FISH > 1.2) rendered disease-free following standard of care therapy. Patients are randomized to receive either AE37+GM-CSF or GM-CSF alone in 6 monthly intradermal inoculations followed by booster inoculations administered every 6 months. Results: The trial has enrolled 254 patients; 105 in the vaccine group (VG) and 149 in the control group (CG). After a median follow-up of 22.3 months, the disease-free survival (DFS) rate in the VG is 90.3% vs 81.1% in the CG (p=.46), a 49% risk reduction. Evaluating patients with low HER2 expression (IHC 1+ or 2+), there are 53 VG patients and 77 CG patients. The groups are well-matched with respect to the percentage of patients with high grade tumors, tumors > 2cm, the rate of node positivity and ER/PR status (all p>.5). The DFS rate in the VG of low HER2 expressers is 89.8% vs 68.2% in the CG (p=.12), a 68% risk reduction. When limiting analyses to patients with TNBC (ER/PR negative, HER2 1+ or 2+), there are 13 VG patients and 23 CG patients. The groups are again well-matched with the exception of control patients having a larger percentage of tumors > 2 cm (70% vs 31%; p=.02). The DFS rate in the VG of TNBC patients is 83.3% vs 47.6% in the CG (p=.23), a 68% risk reduction. Conclusions: Early analyses suggest clinical benefit to vaccination with AE37, particularly in patients with low HER2-expressing tumors. Importantly, the benefit appears to persist in TNBC patients. Patients will continue to be followed per protocol for 5 years; however, these data suggest that a subsequent phase III trial should evaluate the vaccine in patients with low HER2-expressing disease to include TNBC.

Scalp Cooling Alopecia Prevention trial (SCALP) for patients with early stage breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10088-10088 ◽  
Author(s):  
Julie R. Nangia ◽  
Tao Wang ◽  
Cynthia R. C. Osborne ◽  
Polly Ann Niravath ◽  
Kristen Otte ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Randomized Trial ◽  
Interim Analysis ◽  
Randomized Trials ◽  
Early Stage ◽  
Control Group ◽  
P Value ◽  
Scalp Cooling ◽  
Success Rates

10088 Background: Adjuvant chemotherapy decreases the risk of recurrence. However, it has distressing side effects, including alopecia. There are no randomized trials assessing modern scalp cooling to prevent alopecia, and success rates in non-randomized trials have varied. Methods: We conducted a multi-center randomized trial to evaluate the safety and efficacy of the Orbis Paxman Hair Loss Prevention System (OPHLPS) in reducing chemotherapy-induced alopecia. Women with stage I-II breast cancer planned to receive anthracycline- or taxane- based chemotherapy for at least four cycles were eligible and randomized in a 2:1 ratio to scalp-cooling or control. Scalp-cooling was done with the OPHLPS 30 minutes prior to, during and 90 minutes after each chemotherapy. The primary efficacy endpoints were hair preservation and device safety. We planned to enroll 235 subjects to provide 85% power to detect a 20% difference in hair preservation. Secondary endpoints included wig/scarf use and quality of life assessed by the EORTC QLQ-30, HADS and BIS. Subjects will be followed for 5 years for recurrence, overall survival, and site of recurrence. One interim analysis was planned to allow the study to stop early for efficacy after 142 subjects were enrolled and evaluable for the primary endpoint. To maintain the overall type 1 error rate, an O’Brien-Fleming spending function was used (interim boundary p = 0.0061). Results: This is the first randomized trial with modern scalp cooling in the world. For the interim analysis, 142 subjects were evaluable. Among them, 48 (50.5%) out of 95 in the cooling group and 0 (0%) out of 47 in the control group had hair preservation. The one-tailed p-value from the Fisher’s exact test is < 0.0001, which crosses the superiority boundary (p = 0.0061). Thus on 9/26/2016 the DSMB stopped the study early. The interim analysis was presented at SABCS 2016. There are 195 subjects enrolled on this clinical trial, and the final subject will be evaluable for the primary outcome February 2017. The final analysis will be presented. Conclusions: Our trial showed that scalp cooling using OPHLPS is highly effective in hair retention. Paxman Coolers has applied for FDA clearance for the OPHLPS based on the results of the interim analysis. Clinical trial information: NCT01986140.

Validation of MAF biomarker for response prediction to adjuvant bisphosphonates in 2 clinical trials: AZURE and NSABP-B34.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 513-513
Author(s):  
Alexander H. G. Paterson ◽  
Stewart J. Anderson ◽  
Roger Gomis ◽  
Joel [email protected] ◽  
Juan-Carlos Tercero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Clinical Trials ◽  
Disease Free Survival ◽  
Collaborative Group ◽  
Secondary Outcome ◽  
Control Group ◽  
Free Survival ◽  
Disease Free

513 Background: An Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analysis indicates that adjuvant bisphosphonates increase time to bone recurrence and survival in postmenopausal breast cancer patients, but results of individual trials have been inconclusive. Retrospective analyses of AZURE, a trial of adjuvant zoledronic acid, showed MAF (a transcription factor of the AP-1 family) amplification status predicted bisphosphonate benefit independently of menopause for invasive disease-free survival (IDFS) and overall survival (OS). Validation of MAF amplification status as a potential companion diagnostic for adjuvant bisphosphonates was confirmed using NSABP-B34 specimens. Methods: The randomized, placebo-controlled NSABP B-34 study of women with stage 1-3 breast cancer were assigned to adjuvant systemic therapy plus oral clodronate 1600 mg daily or placebo for 3 years. The primary endpoint was disease-free survival (DFS) with overall survival (OS) as a secondary outcome. MAF amplification was assessed by fluorescence in-situ hybridization on anonymized sections of breast tumor tissue in all patients with tumor samples and performed in a laboratory blind to treatment assignment. Protocol and analysis plans were pre-specified. Disease outcomes were analysed using intention to treat principles. Results: 2496 B-34 patients contributed tumor samples (from 2001-2004), of whom 1883 (75%) were evaluable (947 placebo and 936 clodronate). 1515 (80%) tumors were MAF negative (766 placebo and 749 clodronate) and 368 were MAF positive. At median follow-up of 108 months, MAF was prognostic for DFS, OS and bone-metastasis-free survival in the control group (MAF-positive vs MAF-negative: HRDFS=1·39, 95%CI 1·01-1·92; p=0.045; HROS=1·59, 95%CI 1·08-2·33; p=0.018; HRBM=2·03, 95%CI 1·13-3·68; p=0.016). In patients with MAF-negative tumors, clodronate gave higher DFS and OS than controls at 60 months (HRDFS=0·70, 95%CI 0·51-0·94; p=0.020 and HROS=0·59, 95%CI 0·37-0·93; p=0.024), the latter maintained through follow-up (HROS=0·74, 95%CI 0·54-1.00; p=0.047), but not in patients with MAF-positive tumors - consistent with previous AZURE results. Conclusions: MAF benefit prediction from adjuvant bisphosphonates was confirmed using specimens from 2 randomized clinical trials (AZURE and NSABP-B-34) conducted and analyzed in similar manner using the same validated tests and clinical endpoints. These results are evidence towards introducing MAF testing into clinical practice.

Overview of randomized perioperative polychemotherapy trials in women with early-stage breast cancer.

1997 ◽  
Vol 15 (7) ◽  
pp. 2526-2535 ◽  
Author(s):  
P C Clahsen ◽  
C J van de Velde ◽  
A Goldhirsch ◽  
J Rossbach ◽  
M R Sertoli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Clinical Trials ◽  
Early Stage ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Free Survival ◽  
Node Negative ◽  
Disease Free

PURPOSE To determine whether perioperative polychemotherapy (PeCT) can significantly prolong the overall survival of women with early-stage breast cancer. METHODS A meta-analysis that used updated individual patient data from all available randomized trials of PeCT, both published and unpublished, was conducted. Data on 6,093 patients (1,124 deaths and 1,912 recurrences) from five clinical trials were available (median follow-up duration, 5.3 years; maximum, 11.3 years). RESULTS No significant effect of PeCT on overall survival was observed. However, patients who received PeCT had a significantly longer disease-free survival (hazards ratio [HR], 0.89; 95% confidence interval [CI], 0.82 to 0.98; P = .02). Time to local recurrence was significantly prolonged in the PeCT arm (HR, 0.68; 95% CI, 0.58 to 0.80; P < .0001). Likewise, there was a borderline significant difference in favor of PeCT in terms of time to distant metastases (HR, 0.90; 95% CI, 0.81 to 1.00; P = .05). Subgroup analyses suggest that node-negative women benefited the most from treatment. CONCLUSION At present, there is no evidence that PeCT is able to prolong overall survival in patients with early-stage breast cancer; however, further follow-up evaluation is required. PeCT significantly prolongs disease-free survival, especially in node-negative women, which emphasizes once more the need for clinical trials in this subgroup.

Ten-Year Follow-Up of 3 Years of Oral Adjuvant Clodronate Therapy Shows Significant Prevention of Osteoporosis in Early-Stage Breast Cancer

2008 ◽  
Vol 26 (26) ◽  
pp. 4289-4295 ◽  
Author(s):  
Tiina Saarto ◽  
Leena Vehmanen ◽  
Carl Blomqvist ◽  
Inkeri Elomaa
Keyword(s):  
Breast Cancer ◽  
Lumbar Spine ◽  
Cancer Patients ◽  
Predictive Value ◽  
Early Stage ◽  
Control Group ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Spinal Osteoporosis

PurposeWe have previously reported that 3-year adjuvant clodronate treatment prevents bone loss in breast cancer patients. Here we report the 10-year follow-up data of clodronate in the prevention of treatment-related osteoporosis in women with early-stage breast cancer.Patients and MethodsTwo hundred sixty-eight pre- and postmenopausal, node-positive breast cancer patients were randomly assigned to clodronate, 1.6 g orally administered daily, or to control groups for 3 years. Premenopausal women were treated with adjuvant CMF chemotherapy; and postmenopausal women were treated with antiestrogens, either 20 mg tamoxifen or 60 mg toremifene, for 3 years. The bone mineral density (BMD) of the lumbar spine and hip was measured before treatment and at 1, 2, 3, 5, and 10 years after therapy.ResultsEighty-nine disease-free patients were included in the analyses of osteoporosis-free survival. During the 10-year period, 24 of 89 patients were diagnosed with osteoporosis. Fourteen patients developed spinal osteoporosis (three of 41 in the clodronate group, and 11 of 48 in the control group), and 14 of 89 patients were diagnosed with hip osteoporosis (seven of 41 in the clodronate group, and seven of 48 in the control group). The 10-year spinal, osteoporosis-free survival rate was 92.7% in the clodronate group, and 77.0% in the control group (P = .035). No difference was seen in the frequency of hip osteoporosis (85.4% v 82.9%; P = .92). Baseline BMD measurement had a predictive value of 18 of 24 patients (75%) who developed osteoporosis had osteopenia of the lumbar spine at baseline.ConclusionThree years of clodronate therapy significantly reduces the incidence of lumbar spine osteoporosis. Patients at risk of developing osteoporosis are among those who have pretreatment osteopenia, that is, baseline BMD measurement has predictive value.

scholarly journals Effect of Baduanjin exercise intervention on cognitive function and quality of life in women with breast cancer receiving chemotherapy: study protocol of a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xiao-Lin Wei ◽  
Ru-Zhen Yuan ◽  
Yong-Mei Jin ◽  
Shu Li ◽  
Ming-Yue Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Clinical Trial ◽  
Cognitive Function ◽  
Exercise Intervention ◽  
Early Stage ◽  
Early Stage Breast Cancer ◽  
Pharmacological Intervention ◽  
Control Group

Abstract Background More than 50% cognitive impairment was reported by cancer patients before and after medical treatment. However, there are no effective interventions to manage the cognitive problem in women with breast cancer. This pilot study was designed to evaluate the protective effect of Baduanjin exercise on cognitive function and cancer-related symptoms in women with early-stage breast cancer undergoing chemotherapy. Method A single-blinded, randomized control trial was designed. The trial will recruit 70 patients with early-stage breast cancer scheduled to receive chemotherapy from Shanghai in China. All participants will be randomly assigned to (1:1) the supervised Baduanjin group (5 times/week, 30 min each time) or the wait-list control group for 3 months. The effect of Baduanjin exercise intervention will be evaluated by outcome measures including subjective and objective cognitive function, symptoms (fatigue, depression, and anxiety), and health-related quality of life at pre-intervention (T0), 8 weeks (T1), and 12 weeks (T2). The PCI score in the FACT-Cog as the primary cognitive outcome will be reported descriptively, while effect sizes and 95% confidence intervals (CIs) will be calculated. The collected data will be analyzed by using an intention-to-treat principle and linear mixed-effects modeling. Discussion This is the first randomized clinical trial to investigate whether Baduanjin exercise will have a positive role in improving cognitive function in women with breast cancer receiving chemotherapy. If possible, Baduanjin exercise will be a potential non-pharmacological intervention to manage cognitive dysfunction and promote survivorship care among breast cancer survivors. Trial registration Chinese Clinical Trial Registry (ChiCTR) ChiCTR2000033152. Registered on 22 May 2020

scholarly journals The role of functional polymorphisms in oxidative stress-related genes on early-stage breast cancer survival

2021 ◽  
pp. 172460082110111
Author(s):  
Erika Korobeinikova ◽  
Rasa Ugenskiene ◽  
Ruta Insodaite ◽  
Viktoras Rudzianskas ◽  
Jurgita Gudaitiene ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Single Nucleotide Polymorphisms ◽  
Early Stage ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Free Survival ◽  
Disease Free

Background: Genetic variations in oxidative stress-related genes may alter the coded protein level and impact the pathogenesis of breast cancer. Methods: The current study investigated the associations of functional single nucleotide polymorphisms in the NFE2L2, HMOX1, P21, TXNRD2, and ATF3 genes with the early-stage breast cancer clinicopathological characteristics and disease-free survival, metastasis-free survival, and overall survival. A total of 202 Eastern European (Lithuanian) women with primary I–II stage breast cancer were involved. Genotyping of the single nucleotide polymorphisms was performed using TaqMan single nucleotide polymorphisms genotyping assays. Results: The CA+AA genotypes of P21 rs1801270 were significantly less frequent in patients with lymph node metastasis and larger tumor size ( P=0.041 and P=0.022, respectively). The TT genotype in ATF3 rs3125289 had significantly lower risk of estrogen receptor (ER), progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) positive status ( P=0.023, P=0.046, and P=0.040, respectively). In both, univariate and multivariate Cox analysis, TXNRD2 rs1139793 GG genotype vs. GA+AA was a negative prognostic factor for disease-free survival (multivariate hazard ratio (HR) 2.248; P=0.025) and overall survival (multivariate HR 2.248; P=0.029). The ATF3 rs11119982 CC genotype in the genotype model was a negative prognostic factor for disease-free survival (multivariate HR 5.878; P=0.006), metastasis-free survival (multivariate HR 4.759; P=0.018), and overall survival (multivariate HR 3.280; P=0.048). Conclusion: Our findings suggest that P21 rs1801270 is associated with lymph node metastasis and larger tumor size, and ATF3 rs3125289 is associated with ER, PR, and HER2 status. Two potential, novel, early-stage breast cancer survival biomarkers, TXNRD2 rs1139793 and ATF3 rs11119982, were detected. Further investigations are needed to confirm the results of the current study.

Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma (ccRCC): Results from 42-month follow-up of KEYNOTE-426.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4500-4500
Author(s):  
Brian I. Rini ◽  
Elizabeth R. Plimack ◽  
Viktor Stus ◽  
Tom Waddell ◽  
Rustem Gafanov ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Final Analysis ◽  
Similar Proportion ◽  
First Line ◽  
Cell Renal Cell Carcinoma ◽  
Superior Efficacy ◽  
Treatment Naïve ◽  
To Receive ◽  
Safety Signals

4500 Background: In the first interim analysis of the randomized, multicenter, open-label, phase 3 KEYNOTE-426 study (NCT02853331), treatment with pembro + axi significantly improved OS, PFS, and ORR vs sunitinib monotherapy in treatment-naive advanced ccRCC. Extended follow-up (median, 30.6 mo) continued to demonstrate the superior efficacy of pembro + axi vs sunitinib monotherapy in this patient population. Here, we present the results of the prespecified final analysis with 42.8-mo median follow-up. Methods: Treatment-naive patients (pts) with advanced ccRCC, KPS ≥70%, and measurable disease (RECIST v1.1) were randomly assigned 1:1 to receive pembro 200 mg IV Q3W for up to 35 doses + axi 5 mg orally BID or sunitinib 50 mg orally QD on a 4-wk on/2-wk off schedule until progression, intolerable toxicity, or withdrawal. Randomization was stratified by IMDC risk (favorable vs intermediate vs poor) and geographic region (North America vs Western Europe vs Rest of World). Dual primary endpoints were OS and PFS. Secondary endpoints were ORR, DOR, and safety. The protocol-specified final analysis was based on a target of 404 OS events. No formal hypothesis testing was performed because all efficacy endpoints were met previously at the first interim analysis; nominal P values are reported. Results: Overall, 861 pts were randomly assigned to receive pembro + axi (n=432) or sunitinib (n=429). Median duration of follow-up, defined as time from randomization to the database cutoff date, was 42.8 mo (range, 35.6-50.6). At data cutoff, 418 pts had died: 193 (44.7%) of 432 pts in the pembro + axi arm vs 225 (52.4%) of 429 pts in the sunitinib arm. Compared with sunitinib, pembro + axi improved OS (median: 45.7 vs 40.1 mo; HR, 0.73 [95% CI, 0.60-0.88]; P<0.001) and PFS (median: 15.7 vs 11.1 mo; HR, 0.68 [95% CI, 0.58-0.80]; P<0.0001). The 42-mo OS rate was 57.5% with pembro + axi vs 48.5% with sunitinib; the 42-mo PFS rate was 25.1% with pembro + axi vs 10.6% with sunitinib. For pembro + axi vs sunitinib, ORR was 60.4% vs 39.6% ( P<0.0001); CR rate was 10.0% vs 3.5%; median DOR was 23.6 mo (range 1.4+ to 43.4+) vs 15.3 mo (range, 2.3-42.8+). Subsequent anticancer therapy was administered to 47.2% of pts in pembro + axi arm vs 65.5% of pts in sunitinib arm. Although a similar proportion of pts in each arm received VEGF/VEGFR inhibitors, only 10.2% of pts in the pembro + axi arm received subsequent treatment with a PD-1/L1 inhibitor compared to 48.7% of pts in the sunitinib arm. No new safety signals were observed. Conclusions: With a median follow-up of 42.8 mo, this is the longest follow-up of an anti-PD–1/L1 immunotherapy combined with a VEGF/VEGFR inhibitor for first-line RCC. These results show that pembro + axi continues to demonstrate superior efficacy over sunitinib with respect to OS, PFS, and ORR, with no new safety signals. Clinical trial information: NCT02853331.

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