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  • 1
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    Abstract PD8-05: Overall survival (OS) results from the phase III PHENIX trial of HER2+ metastatic breast cancer treated with pyrotinib plus capecitabine
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 4_Supplement ( 2022-02-15), p. PD8-05-PD8-05
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. PD8-05-PD8-05
    Abstract: Background: Pyrotinib (an irreversible tyrosine kinase inhibitor targeting EGFR, HER2, and HER4) plus capecitabine previously demonstrated a statistically significant improvement in progression-free survival (PFS) over placebo plus capecitabine for HER2-positive local relapsed or metastatic breast cancer after prior trastuzumab and taxanes in the interim analysis of the PHENIX trial (NCT02973737; Jiang Z et al. Oral presentation at ASCO 2019, Abstract 1001). It is shown that patients also benefit from subsequent pyrotinib monotherapy after progressed on capecitabine alone. Here we present an updated OS from a follow-up period with a median of 42.1 months. Methods: This PHENIX trial enrolled patients with HER2-positive local relapsed or metastatic breast cancer who had received prior trastuzumab and taxanes and up to two prior lines of chemotherapy for relapsed or metastatic disease. Eligible patients were randomized 2:1 to receive pyrotinib (400 mg orally once daily) in combination with capecitabine (1000 mg/m2 orally twice daily on days 1-14 for 21-day cycles; P+C group) or placebo plus capecitabine followed by pyrotinib monotherapy upon disease progression (C-P group). Randomization was stratified by the presence of visceral disease (yes vs. no) and the hormone receptor status (estrogen receptor [ER]- and/or progesterone receptor [PR] -positive vs. ER- and PR-negative). The primary endpoint was the independent review committee-assessed PFS. The data cutoff for the updated OS analysis was January 15, 2021. Results: A total of 279 eligible patients were randomized, with 185 to P+C group and 94 to C-P group. As of data cutoff, the median duration of follow-up was 41.7 months (95% CI 40.2-42.4) in P+C group and 43.1 months (95% CI 38.8-44.5) in C-P group. 71 out of 94 patients who progressed on placebo plus capecitabine received pyrotinib monotherapy as the first subsequent anti-cancer therapy according to protocol. Excluding the protocol prespecified pyrotinib monotherapy, 129 (69.7%) patients in the P+C group and 74 (78.7%) patients in the C-P group received anti-cancer therapy after discontinuing study treatment, and 107 (57.8%) patients and 61 (64.9%) patients received post-discontinuation anti-HER2 drugs, respectively. 98 (53.0%) of the 185 patients in P+C group and 59 (62.8%) of the 94 patients in C-P group died by the time of data cutoff. Kaplan-Meier estimated median OS was 34.9 months (95% CI 28.4-42.1) in P+C group and 23.6 months (95% CI 19.3-34.4) in C-P group (HR 0.74, 95% CI 0.54-1.02; p=0.068). The 2-year OS rate was 65.2% (95% CI 57.6%-71.8%) versus 48.9% (95% CI 38.1%-58.7%), respectively. Subgroup analyses of OS were generally consistent with the overall result (Table 1). Conclusion: The updated OS analysis highlighted the long-term efficacy of pyrotinib plus capecitabine in pretreated HER2-positive local relapsed or metastatic breast cancer. We did not observe a statistically significant difference in OS between pyrotinib plus capecitabine group and capecitabine group followed by subsequent pyrotinib monotherapy upon disease progression. Table 1.Subgroup analysis of OS.Pyrotinib plus capecitabine (n=185)Placebo plus capecitabine (n=94)HR (95% CI) *Brain metastasesPresentEvents14/21 (66.7)8/10 (80.0)Median OS22.9 (19.7-35.0)17.3 (1.6-34.4)0.77 (0.32-1.84)AbsentEvents84/164 (51.2)51/84 (60.7)Median OS36.7 (30.7-43.0)23.6 (21.5-40.4)0.72 (0.51-1.02)Previous chemotherapyNoneEvents29/60 (48.3)12/22 (54.5)Median OS37.5 (34.2-NA)32.6 (18.9-NA)0.75 (0.38-1.47)1 lineEvents34/70 (48.6)27/47 (57.4)Median OS35.6 (25.9-NA)31.6 (18.0-NA)0.73 (0.44-1.21)2 linesEvents30/44 (68.2)13/18 (72.2)Median OS21.1 (13.6-33.4)15.9 (5.4-44.0)0.77 (0.40-1.49)Data are n/N (%) or median (95% CI). NA, not available. *HRs are from unstratified analyses. Citation Format: Zefei Jiang, Min Yan, Li Bian, Tao Wang, Xichun Hu, Qingyuan Zhang, Quchang Ouyang, Jifeng Feng, Yongmei Yin, Tao Sun, Zhongsheng Tong, Xiaojia Wang, Herui Yao, Shuping Jiang, Xiaoyu Zhu, Jianjun Zou. Overall survival (OS) results from the phase III PHENIX trial of HER2+ metastatic breast cancer treated with pyrotinib plus capecitabine [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD8-05.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS21-PD8-05
    RVK:
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    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 2
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    Pyrotinib or Lapatinib Combined With Capecitabine in HER2–Positive Metastatic Breast Cancer With Prior Taxanes, Anthracyclines, and/or Trastuzumab: A Randomized, Phase II Study
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 29 ( 2019-10-10), p. 2610-2619
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 29 ( 2019-10-10), p. 2610-2619
    Abstract: Pyrotinib, an irreversible pan-ErbB inhibitor, showed promising antitumor activity and acceptable tolerability in a phase I trial. We assessed the efficacy and tolerability of pyrotinib versus lapatinib, both in combination with capecitabine, in women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in an open-label, multicenter, randomized phase II study. PATIENTS AND METHODS Chinese patients with HER2-positive relapsed or metastatic breast cancer previously treated with taxanes, anthracyclines, and/or trastuzumab were assigned (1:1) to receive 400 mg pyrotinib or lapatinib 1,250 mg orally once per day for 21-day cycles in combination with capecitabine (1,000 mg/m 2 orally twice per day on days 1 to 14). The primary end point was investigator-assessed overall response rate per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. RESULTS Between May 29, 2015, and March 15, 2016, 128 eligible patients were randomly assigned to the pyrotinib (n = 65) or lapatinib (n = 63) treatment groups. The overall response rate was 78.5% (95% CI, 68.5% to 88.5%) with pyrotinib and 57.1% (95% CI, 44.9% to 69.4%) with lapatinib (treatment difference, 21.3%; 95% CI, 4.0% to 38.7%; P = .01). The median progression-free survival was 18.1 months (95% CI, 13.9 months to not reached) with pyrotinib and 7.0 months (95% CI, 5.6 to 9.8 months) with lapatinib (adjusted hazard ratio, 0.36; 95% CI, 0.23 to 0.58; P 〈 .001). The most frequent grade 3 to 4 adverse events were hand-foot syndrome in 16 of 65 patients (24.6%) in the pyrotinib group versus 13 of 63 (20.6%) in the lapatinib group; diarrhea in 10 patients (15.4%) versus three patients (4.8%), respectively; and decreased neutrophil count in six patients (9.2%) versus two patients (3.2%), respectively. CONCLUSION In women with HER2-positive metastatic breast cancer previously treated with taxanes, anthracyclines, and/or trastuzumab, pyrotinib plus capecitabine yielded statistically significant better overall response rate and progression-free survival than lapatinib plus capecitabine in this randomized phase II trial.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.19.00108
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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  • 3
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    Pyrotinib combined with capecitabine in women with HER2+ metastatic breast cancer previously treated with trastuzumab and taxanes: A randomized phase III study.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 1001-1001
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 1001-1001
    Abstract: 1001 Background: Pyrotinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor, showed promising anti-tumour activity and acceptable tolerability in patients with HER2+ metastatic breast cancer (MBC) in phase 1/2 trials. Methods: This double-blinded, multicentre, randomised phase 3 trial was conducted in Chinese patients with HER2+ MBC previously treated with taxanes and trastuzumab. Patients were randomly assigned (2:1) to receive 400 mg pyrotinib or placebo orally once daily for 21-day cycles in combination with capecitabine (1000 mg/m 2 orally twice daily on days 1–14). The primary endpoint (IRC-assessed progression free survival [PFS]) was assessed in patients who received ≥1 dose of study treatment. Patients whose disease progressed on placebo plus capecitabine received subsequent single agent pyrotinib. Results: Between July, 2016 and November, 2017, 279 patients were randomised to pyrotinib plus capecitabine (n = 185) or placebo plus capecitabine (n = 94) arms. The median PFS was 11.1 months (95% CI 9.66, 16.53) in the pyrotinib plus capecitabine arm and 4.1 months (95% CI 2.79, 4.17) in the placebo plus capecitabine arm. seventy-one patients in placebo plus capecitabine arm received subsequent pyrotinib, showing single-agent response rate of 38.0% (95%CI 26.7%, 49.3%) and median PFS of 5.5 months (95% CI 4.07, 6.90). The most frequent (≥5%) treatment-related ≥ grade 3 adverse events were diarrhoea (30.8% vs 12.8% ) and hand-foot syndrome (15.7% vs 5.3%). Conclusions: In women with HER2+ MBC previously treated with taxanes and trastuzumab, pyrotinib plus capecitabine yield statistically significant better PFS. Pyrotinib monotherapy showed anti-tumour activity. Clinical trial information: NCT02973737. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.1001
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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  • 4
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    Abstract P1-13-07: A phase III study of fulvestrant 500 mg versus 250 mg in postmenopausal Chinese women with advanced breast cancer and disease progression following failure on prior antiestrogen or aromatase inhibitor therapy: Supporting superior clinical benefit for the
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 9_Supplement ( 2015-05-01), p. P1-13-07-P1-13-07
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 9_Supplement ( 2015-05-01), p. P1-13-07-P1-13-07
    Abstract: Background: In the international Phase III COmparisoN of Faslodex In Recurrent or Metastatic breast cancer (CONFIRM) study, fulvestrant 500 mg was associated with significantly longer progression-free survival (PFS) over the 250 mg dose (hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.68, 0.94; p=0.006) in postmenopausal women with advanced breast cancer (ABC) following failure on prior endocrine therapy. There were no clinically meaningful differences between the treatment groups in terms of the incidence or severity of adverse events. The present study was designed to compare the efficacy and safety of fulvestrant 500 mg versus 250 mg in a Chinese population for registration purposes. Methods: This was a Phase III randomized, double-blind study in a Chinese population (ClinicalTrials.gov: NCT01300351). Postmenopausal women with estrogen receptor positive (ER+) ABC following failure on prior endocrine (antiestrogen [AO] or aromatase inhibitor [AI] ) therapy were randomized 1:1 to fulvestrant 500 mg or 250 mg. Patients (pts) were stratified by post-AO/post-AI status and enrollment of post-AI pts was capped at 45%. Primary study endpoint was PFS. Consistency with the global CONFIRM study was to be concluded if the HR for the treatment comparison of PFS was & lt;1 (full analysis set; stratified log-rank test); the study was not powered to detect significant differences between treatment groups. Secondary endpoints included pharmacokinetics, ORR, CBR, DoR, DoCB, safety and tolerability. Results: 221 pts were randomized to fulvestrant 500 mg (n=111) or fulvestrant 250 mg (n=110). 121 pts were in the post-AO subgroup and 100 pts were in the post-AI subgroup. Demographic and baseline characteristics were balanced between fulvestrant 500 mg and fulvestrant 250 mg and comparable with those in the global CONFIRM study. 98% (119/121) in the post-AO subgroup and 92% (92/100) in the post-AI subgroup had adjuvant endocrine therapy, while only 12% (14/121) in the post-AO subgroup and 51% (51/100) in the post-AI subgroup used salvage endocrine therapy. At the time of the primary analysis, 152 progression events (69%) had occurred (post-AO 59% [71/121]; post-AI 81% [81/100] ). Median PFS was 8.0 months (m) in the fulvestrant 500 mg group vs 4.0 m in the 250 mg group (HR 0.75; 95% CI 0.54, 1.03; p=0.078); the predefined criterion for consistency with the global CONFIRM study was met. In a predefined subgroup analysis of PFS, the HR for fulvestrant 500 mg vs 250 mg was & lt;1 in both post-AO (median PFS 8.1 m vs 5.6 m; HR 0.86; 95% CI 0.54, 1.37) and post-AI (median PFS 5.8 m vs 2.9 m; HR 0.65; 95% CI 0.42, 1.03) subgroups. Secondary endpoints favored fulvestrant 500 mg over 250 mg, with the exception of median DoR. Safety and tolerability profiles were consistent with the known safety profile of fulvestrant. Conclusions: Data from the present study support the superior clinical benefit of fulvestrant 500 mg vs 250 mg demonstrated in the global CONFIRM study, in postmenopausal Chinese women with ER+ ABC. Hazard ratios favoring fulvestrant 500 mg were observed in both the post-AO and post-AI settings. Citation Format: Zefei Jiang, Qingyuan Zhang, Zhimin Shao, Kunwei Shen, Li Li, Jifeng Feng, Zhongseng Tong, Kangsheng Gu, Xiaojia Wang, Binghe Xu, Guofang Sun, Huifang Chen, Yuri Rukazenkov. A phase III study of fulvestrant 500 mg versus 250 mg in postmenopausal Chinese women with advanced breast cancer and disease progression following failure on prior antiestrogen or aromatase inhibitor therapy: Supporting superior clinical benefit for the [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-13-07.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS14-P1-13-07
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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  • 5
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    Abstract P3-10-02: Gemcitabine with cisplatin or paclitaxel in metastatic triple-negative breast cancer
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 9_Supplement ( 2015-05-01), p. P3-10-02-P3-10-02
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 9_Supplement ( 2015-05-01), p. P3-10-02-P3-10-02
    Abstract: Background: There is still no standard chemotherapy for patients with metastatic triple-negative breast cancer (mTNBC). Our previous phase II pilot trial with first-line gemcitabine and cisplatin combination (GP) in patients with mTNBC (clinicaltrials.gov Identifier: NCT00601159) showed a median progression-free survival (PFS) of 6.2 months. In this Chinese Breast Cancer Study Group (CBCSG) 006 trial (clinicaltrials.gov Identifier: NCT01287624) we explored in a randomized trial the role of the less costly GP regimen versus the standard GT [Gemcitibine + paclitaxel] chemotherapy for the metastatic breast cancer as a first line treatment for mTNBC. Trial objectives: progression free survival [PFS]; overall survival [OS] ; and toxicity. Methods: In the trial with a hybrid trial design incorporating a formal test of superiority as well as noninferiority, mTNBC patients with no previous chemotherapy for metastatic disease were randomly assigned to receive either GP regimen (G/P: 1250 mg/m2 d1,8/ 75 mg/m2 d1) or the GT regimen (same G; T: 175 mg/m2 d1). Results: Between Jan. 2011 and Nov., 2013, 236 patients were randomized [118 patients / arm], and all received at least one dose of assigned chemotherapy. As of Mar. 20, 2014, the intent-to-treat analysis showed 201 recurrences and 97 deaths. Objective response rates of GP vs GT were 67.9% vs. 50.4% (P= 0.008), with median PFS of 232 vs. 194 days (HR=0.692, 95% CI 0.523-0.915; P= 0.009). Overall survival of patients from the GP vs. the GT arms was median 672 vs. 556 days (HR=0.902, 95% CI 0.605-1.344; P= 0.611). Significant differences in grade 3/4 adverse events were seen for nausea, vomiting, anemia and thrombocytopenia [GP vs. GT, 6.8 vs. 0.8%; 11.0 vs. 0.8%; 33.1 vs. 51.0%; and 32.2 vs. 2.5%, respectively]. In addition, assessment of adverse events of any grade showed the GP regimen had more anorexia, constipation, hypomagnesemia and hypokalemia, while GT regimen had significantly more alopecia and peripheral neuropathy. The delivered relative dose intensity was & gt; 90% for all three drugs, with the total number of delivered cycles of chemotherapy in GP and GT arms being 654 and 648 [average 5.54 and 5.49 /patient], respectively. Conclusions: 1.The Gemcitabine + Platinum is superior to Gemcitabine + Paclitaxel in terms of objective response rates and duration of PFS. 2.While grade 3 / 4 nausea & vomiting, and anemia, were heavier for the GP combination, the delivery of chemotherapy and average number of cycles delivered were comparable between the two arms. 3.Overall survival data will be updated on the conference to indicate the long-term effect of the somehow more toxic GP regimen, which shows nevertheless superiority of response rates and of the PFS over the more costly GT regimen. Citation Format: Xichun Hu, Binghe Xu, Li Cai, Zhonghua Wang, Biyun Wang, Jian Zhang, Yuee Teng, Zhongsheng Tong, Yueyin Pan, Yongmei Yin, Changping Wu, Zefei Jiang, Xiaojia Wang, Guyin Lou, Donggeng Liu, Jifeng Feng, Jianfeng Luo, Jiong Wu, Zhimin Shao, Joseph Ragaz. Gemcitabine with cisplatin or paclitaxel in metastatic triple-negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-10-02.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS14-P3-10-02
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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  • 6
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    Abstract S6-01: Phase 3, randomized, double-blind, placebo-controlled multicenter trial of daily everolimus plus weekly trastuzumab and paclitaxel as first-line therapy in women with HER2+ advanced breast cancer: BOLERO-1
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 9_Supplement ( 2015-05-01), p. S6-01-S6-01
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 9_Supplement ( 2015-05-01), p. S6-01-S6-01
    Abstract: Background: Everolimus (EVE), an inhibitor of mammalian target of rapamycin (mTOR), is a protein kinase central to a number of signaling pathways regulating cell growth and proliferation. In early studies, EVE showed antitumor activity in breast cancer and synergy with both trastuzumab (TRAS) and paclitaxel. The international BOLERO-1 study is being conducted to evaluate the addition of EVE to TRAS plus paclitaxel as first-line therapy for HER2+ advanced breast cancer. Methods: In this phase 3 randomized trial, 719 adult women with HER2+ advanced breast cancer who had not received prior TRAS or chemotherapy in the advanced setting were randomized 2:1 to receive either EVE or placebo (10 mg) in combination with weekly paclitaxel and TRAS. The two primary objectives were to compare the progression-free survivals (PFS) of everolimus/trastuzumab/paclitaxel and trastuzumab/paclitaxel/placebo in both the full population and in the Hormone Receptor negative (HR-) subpopulation. Secondary endpoints included survival, response rate, and safety. The final analysis was performed after 420 PFS events were observed in the full population. Results: In the full population, the median age was 53 years, 70.4% had visceral metastases, 56.1% had ER and/or PgR +ve disease, and 43.3% had ≥ 3 metastatic sites. Previous adjuvant therapy included TRAS (11.4%) and taxane (24.7%). Conclusions: The data from the final analysis will be available in October 2014. PFS, safety, and secondary efficacy endpoints will be presented at SABCS 2014. (Funded by Novartis; BOLERO-1 ClinicalTrials.gov number, NCT00876395.) Citation Format: Sara A Hurvitz, Fabrice Andre, Zefei Jiang, Zhimin Shao, Silvia P Neciosup, Max S Mano, Ling-Min Tseng, Qingyuan Zhang, Kunwei Shen, Donggeng Liu, Lydia M Dreosti, Jifeng Feng, Howard A Burris, Masakazu Toi, Marc E Buyse, David Cabaribere, Mary-Ann Lindsay, Tiffany Kunz, Shantha Rao, Lida B Pacaud, Tetiana Taran, Dennis Slamon. Phase 3, randomized, double-blind, placebo-controlled multicenter trial of daily everolimus plus weekly trastuzumab and paclitaxel as first-line therapy in women with HER2+ advanced breast cancer: BOLERO-1 [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr S6-01.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS14-S6-01
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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  • 7
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    Abstract PS13-25: Management of abemaciclib associated diarrhea in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: Analysis of the MONARCH plus study
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 4_Supplement ( 2021-02-15), p. PS13-25-PS13-25
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 4_Supplement ( 2021-02-15), p. PS13-25-PS13-25
    Abstract: Background: In the phase III MONARCH plus study (NCT02763566) the cyclin-dependent kinase (CDK) 4 & 6 inhibitor abemaciclib in combination with non-steroidal aromatase inhibitors (NSAI) or with fulvestrant compared with placebo demonstrated its efficacy and acceptable safety profile at interim analysis in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) locoregionally recurrent or metastatic breast cancer. One of the most common treatment-emergent adverse event (TEAE) was diarrhea, typically low grade and of early onset. We will further characterize abemaciclib-associated diarrhea and describe its management in MONARCH plus trial. Methods: MONARCH plus study included two cohorts of patients. Cohort A enrolled patients with initial treatment of endocrine therapy, received abemaciclib or placebo plus NSAI (anastrozole or letrozole); Cohort B enrolled patients who progressed on prior endocrine therapy, receiving abemaciclib or placebo plus fulvestrant. The relative dose intensity was defined as the percentage of actual dose received relative to the planned dose. The severity of diarrhea was reported by investigators and graded according to Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0). Further analysis on diarrhea included time to onset, duration, supportive medication and dose modifications. Progression-free survival (PFS) was defined as time from randomization to death or progression (RECIST v1.1), and a stratified Cox proportional hazard model was used to estimate the hazard ratio (HR) between study intervention arm and placebo arm. Results: The median relative dose intensity of abemaciclib in abemaciclib plus NSAI arm and abemaciclib plus fulvestrant arm were 96.77% and 96.30% respectively. In abemaciclib plus NSAI arm and abemaciclib plus fulvestrant arm, the median time to onset of first reported diarrhea was 7 and 6 days and majority of diarrhea events occurred early (66.3% and 71.2% of patients reported diarrhea in Cycle 1 respectively). Diarrhea was typically of low grade (3.9% and 1.9% of patients reported Grade 3 in abemaciclib plus NSAI arm and abemaciclib plus fulvestrant arm, no Grade 4 diarrhea was reported in either arm). Median duration of grade ≥ 3 diarrhea was 2.5 and 3.5 days. Diarrhea was managed by dose adjustments and/or supportive medication (Table 1). Dose reductions were present in 2.0% and 2.9% of patients, and anti-diarrhea therapy was received in 30.2% and 32.7% of patients with abemaciclib plus NSAI and abemaciclib plus fulvestrant arm, respectively. As data cutoff, most diarrhea events were reported as resolved, and the incidence dropped below 10% (Grade 2) and 1% (Grade 3) by Cycle 2 in both arms and kept low incidence over time. Compared to the placebo arm, patients treated with abemaciclib combination who reported diarrhea within the first 7 days (abemaciclib + NSAI, HR [95% CI]: 0.289 [0.166, 0.502] ; abemaciclib + fulvestrant, HR [95% CI]: 0.371 [0.213, 0.647] ) had significant improvement in PFS. Conclusion: Majority of diarrhea events were of low grade in severity and well managed by anti-diarrheal medications, dose omissions or/and dose reductions in MONARCH plus patients. Table 1. Summary of dose adjustments and supportive medications in patients experiencing diarrheaCohort ACohort BAbemaciclib + NSAIAbemaciclib + FulvestrantN = 205N = 104Diarrhea (any grade), n (%)164 (80.0)82 (78.8)1105 (51.2)52 (50.0)251 (24.9)28 (26.9)38 (3.9)2 (1.9)Outcome, number of events, n796333Recovered/resolved, n (%)757 (95.1)318 (95.5)Not recovered/resolved, n (%)17 (2.1)7 (2.1)Treatment change, n (%)Dose reduction4 (2.0)3 (2.9)Dose omission3 (1.5)3 (2.9)Treatment discontinuation00Anti-diarrhea therapies, n (%)62 (30.2)34 (32.7)loperamide48 (23.4)21 (20.2)berberine6 (2.9)6 (5.8) Citation Format: Zefei Jiang, Xichun Hu, Qingyuan Zhang, Tao Sun, Yongmei Yin, Huiping Li, Min Yan, Zhongsheng Tong, Christina Pimentel Oppermann, Yunpeng Liu, Romulo Costa, Man Li, Xi Chen, Ying Cheng, Quchang Ouyang, Ning Liao, Xiaojia Wang, Xinhong Wu, Jifeng Feng, Roberto Hegg, Govindbabu Kanaka Setty, Amit Agarwal, Jyoti Bajpai, Jing Cheng, Gustavo Girotto, Chanchal Goswami, Wenjing Hu, Jian Huang, MA Coccia Portugal, Jin Yang, Rongsheng Zheng, Fabio Andre Franke, Qiang Liu, Yunjiang Liu, Yongkui Lu, Cristiano Souza, Shiying Yu, Nalini Kilara, Harsha Panchal, Ashish Singh, Shona Nag, Jian Liu, Bernardo Rapoport, Neonyana Keorapetse Rebecca Tabane, Hongxia Wang, Ning Wang, Rubing Han, Wanli Zhang. Management of abemaciclib associated diarrhea in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: Analysis of the MONARCH plus study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-25.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS20-PS13-25
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
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    Multicenter phase II study of apatinib, a novel VEGFR inhibitor in heavily pretreated patients with metastatic triple-negative breast cancer : Apatinib in metastatic TNBC
    Wiley ; 2014
    In:  International Journal of Cancer Vol. 135, No. 8 ( 2014-10-15), p. 1961-1969
    Details
    In: International Journal of Cancer, Wiley, Vol. 135, No. 8 ( 2014-10-15), p. 1961-1969
    Type of Medium: Online Resource
    ISSN: 0020-7136
    URL: Article
    DOI: 10.1002/ijc.28829
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2014
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    detail.hit.zdb_id: 1474822-8
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