Palbociclib/ribociclib

Palbociclib/ribociclib Reactions 1704, p293 - 2 Jun 2018 Acquired resistance during treatment of metastatic breast cancer: 3 case reports In a study, 3 women were described [ages not clearly stated], of whom, two women developed acquired resistance to palbociclib, while the remaining one woman developed acquired resistance ribociclib during treatment of metastatic breast cancer [not all dosages and routes stated]. Patient 1: The woman, who was born in 1948, was diagnosed with invasive ductal carcinoma in 2004. In August 2009, at the age of 59 years, she was diagnosed with multifocal recurrent hepatic metastases and recurrence of breast cancer. She received treatment with various drugs. In late November 2016, she started receiving treatment with oral palbociclib 125 mg/day for 3 weeks, followed by 1 week off and concomitant fulvestrant. She continued to receive palbociclib until mid-April 2017, when significant hepatic progression was confirmed. On the same day, the peripheral blood sample was collected and circulating tumour DNA (ctDNA) next-generation sequencing (NGS) was performed, which revealed a substitution in donor splicing site of exon 8 of the RB1 gene, suggestive of acquired resistance to palbociclib. A tissue based NGS analysis of a hepatic metastasis biopsy collected three months prior to the initiation of palbociclib did not show and RB1 mutation. Patient 2: The woman, who was born in 1958, was diagnosed with invasive ductal carcinoma in 2008. She received treatment with various drugs. In May 2016, at the age of 58 years, she was diagnosed with metastasis in the right hepatic lobe and metastatic breast cancer. In June 2016, she started receiving treatment with oral palbociclib 125 mg/day for 3 weeks, followed by 1 week off and concomitant fulvestrant. In June 2016, there were no RB1 mutations noted on the ctDNA assay before starting the palbociclib therapy. Also, genomic testing conducted on the tissue-based hepatic metastasis in May 2016 prior to start of palbociclib did not detect RB1 mutation. After disease progression in February 2017, a repeat ctDNA testing showed many molecular alterations, including a substitution in donor splicing site of exon 22 of RB1 gene, suggestive of acquired resistance to palbociclib. Patient 3: The woman, who was born in 1949, was diagnosed with invasive ductal carcinoma in 2000. She received treatment with various drugs. In January 2015, at the age of 66 years, she was with metastatic breast cancer. In the same month, she stated receiving treatment with ribociclib and concomitant letrozole as part of a clinical trial. She responded to ribociclib until April 2016, when her disease progressed to worsening parenchymal pulmonary and hepatic metastases. The liver biopsy obtained in November 2015, while her disease was still responsive to ribociclib, did not reveal any evidence of an RB1 mutation. In March 2016, her disease progressed, while she was on ribociclib. Hence, she was treated with capecitabine, followed by nab paclitaxel chemotherapy. In March 2017, ctDNA analysis showed a p.His483Tyr RB1 variant in exon 16, suggestive of acquired resistance to ribociclib. Author comment: "In conclusion, we have demonstrated the presence of multiple somatic RB1 mutations in ctDNA samples collected following initial response followed by disease progression on palbociclib or ribociclib in three patients with ERHER2 mBC." Condorelli R, et al. Polyclonal RB1 mutations and acquired resistance to CDK 4/6 inhibitors in patients with metastatic breast cancer. Annals of Oncology 29: 640-645, No. 3, Mar 2018. Available from: URL: http://doi.org/10.1093/annonc/ mdx784 - France 803323864 0114-9954/18/1704-0001/$14.95 Adis © 2018 Springer International Publishing AG. All rights reserved Reactions 2 Jun 2018 No. 1704 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Reactions Weekly Springer Journals

Palbociclib/ribociclib

Reactions Weekly , Volume 1704 (1) – Jun 2, 2018
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Publisher
Springer International Publishing
Copyright
Copyright © 2018 by Springer International Publishing AG, part of Springer Nature
Subject
Medicine & Public Health; Drug Safety and Pharmacovigilance; Pharmacology/Toxicology
ISSN
0114-9954
eISSN
1179-2051
D.O.I.
10.1007/s40278-018-46936-3
Publisher site
See Article on Publisher Site

Abstract

Reactions 1704, p293 - 2 Jun 2018 Acquired resistance during treatment of metastatic breast cancer: 3 case reports In a study, 3 women were described [ages not clearly stated], of whom, two women developed acquired resistance to palbociclib, while the remaining one woman developed acquired resistance ribociclib during treatment of metastatic breast cancer [not all dosages and routes stated]. Patient 1: The woman, who was born in 1948, was diagnosed with invasive ductal carcinoma in 2004. In August 2009, at the age of 59 years, she was diagnosed with multifocal recurrent hepatic metastases and recurrence of breast cancer. She received treatment with various drugs. In late November 2016, she started receiving treatment with oral palbociclib 125 mg/day for 3 weeks, followed by 1 week off and concomitant fulvestrant. She continued to receive palbociclib until mid-April 2017, when significant hepatic progression was confirmed. On the same day, the peripheral blood sample was collected and circulating tumour DNA (ctDNA) next-generation sequencing (NGS) was performed, which revealed a substitution in donor splicing site of exon 8 of the RB1 gene, suggestive of acquired resistance to palbociclib. A tissue based NGS analysis of a hepatic metastasis biopsy collected three months prior to the initiation of palbociclib did not show and RB1 mutation. Patient 2: The woman, who was born in 1958, was diagnosed with invasive ductal carcinoma in 2008. She received treatment with various drugs. In May 2016, at the age of 58 years, she was diagnosed with metastasis in the right hepatic lobe and metastatic breast cancer. In June 2016, she started receiving treatment with oral palbociclib 125 mg/day for 3 weeks, followed by 1 week off and concomitant fulvestrant. In June 2016, there were no RB1 mutations noted on the ctDNA assay before starting the palbociclib therapy. Also, genomic testing conducted on the tissue-based hepatic metastasis in May 2016 prior to start of palbociclib did not detect RB1 mutation. After disease progression in February 2017, a repeat ctDNA testing showed many molecular alterations, including a substitution in donor splicing site of exon 22 of RB1 gene, suggestive of acquired resistance to palbociclib. Patient 3: The woman, who was born in 1949, was diagnosed with invasive ductal carcinoma in 2000. She received treatment with various drugs. In January 2015, at the age of 66 years, she was with metastatic breast cancer. In the same month, she stated receiving treatment with ribociclib and concomitant letrozole as part of a clinical trial. She responded to ribociclib until April 2016, when her disease progressed to worsening parenchymal pulmonary and hepatic metastases. The liver biopsy obtained in November 2015, while her disease was still responsive to ribociclib, did not reveal any evidence of an RB1 mutation. In March 2016, her disease progressed, while she was on ribociclib. Hence, she was treated with capecitabine, followed by nab paclitaxel chemotherapy. In March 2017, ctDNA analysis showed a p.His483Tyr RB1 variant in exon 16, suggestive of acquired resistance to ribociclib. Author comment: "In conclusion, we have demonstrated the presence of multiple somatic RB1 mutations in ctDNA samples collected following initial response followed by disease progression on palbociclib or ribociclib in three patients with ERHER2 mBC." Condorelli R, et al. Polyclonal RB1 mutations and acquired resistance to CDK 4/6 inhibitors in patients with metastatic breast cancer. Annals of Oncology 29: 640-645, No. 3, Mar 2018. Available from: URL: http://doi.org/10.1093/annonc/ mdx784 - France 803323864 0114-9954/18/1704-0001/$14.95 Adis © 2018 Springer International Publishing AG. All rights reserved Reactions 2 Jun 2018 No. 1704

Journal

Reactions WeeklySpringer Journals

Published: Jun 2, 2018

References

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