bims-cyhorp 2022-05-22 papers

Issue of 2022–05–22
five papers selected by
Piotr Okupski,

J Oncol Pharm Pract. 2022 May 16. 10781552221101799

Vortex keratopathy associated with ribociclib.

Alper Türkel, Sibel Özdoğan, Emre Yekedüz, Erdoğan Şeyran, Cengiz Karaçin, Öztürk Ateş.

INTRODUCTION: Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors are the new generation drugs that have been started to be used in our clinical practice recently. These drugs have been shown to have better progression-free survival compared to standard therapy in patients with hormone receptor-positive (HR) and human epidermal growth factor receptor 2 (HER-2)-negative breast cancer. The most common side effects of CDK 4-6 inhibitors are neutropenia, nausea, leukopenia, fatigue, and diarrhea. This case demonstrated vortex keratopathy in both eyes, a rare condition in patients with breast cancer treated with ribociclib.
CASE REPORT: A 68-year-old female patient was diagnosed with locally advanced HR (+)/HER2 (-) breast cancer in March 2015. In June 2021, bone metastases were detected. The patient was started on ribociclib and fulvestrant. After three cycles of ribociclib and fulvestrant treatment, she was admitted with the complaint of blurred vision in her left eye. Slit-lamp biomicroscopy examination revealed subepithelial haze with central subepithelial whorls in both corneas, more in the left eye, and also a mild punctate epithelial staining was observed with the application of fluorescein dye.
MANAGEMENT AND OUTCOME: Ribociclib treatment was immediately discontinued and no changes were observed in the cornea and vision levels during the one-month follow-up.
DISCUSSION: Routine and regular follow-up eye examinations in breast cancer patients treated with ribociclib may benefit patients in our daily clinical practice and may help us to detect side effects at an early stage and to manage them more effectively.

Keywords: Ribociclib; breast cancer; combination treatment; cyclin-dependent kinases 4 and 6; vortex keratopathy

DOI: https://doi.org/10.1177/10781552221101799

Clin Cancer Res. 2022 May 18. pii: clincanres.3811.2021. [Epub ahead of print]

VERONICA: Randomized Phase 2 Study of Fulvestrant and Venetoclax in ER-Positive Metastatic Breast Cancer Post-CDK4/6 Inhibitors - Efficacy, Safety, Biomarker Results.

Geoffrey J Lindeman, Tharu M Fernando, Rebecca Bowen, Katarzyna J Jerzak, Xinni Song, Thomas Decker, Frances Boyle, Steven McCune, Anne Armstrong, Catherine Shannon, Gianfilippo Bertelli, Ching-Wei Chang, Rupal Desai, Kushagra Gupta, Timothy R Wilson, Aulde Flechais, Aditya Bardia.

PURPOSE: Despite promising activity in hematopoietic malignancies, efficacy of the B-cell lymphoma 2 (BCL) inhibitor venetoclax in solid tumors is unknown. We report the prespecified VERONICA primary results, a randomized phase 2 clinical trial evaluating venetoclax and fulvestrant in estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer, post-cyclin-dependent kinase (CDK) 4/6 inhibitor progression.
PATIENTS AND METHODS: Pre-/postmenopausal females {greater than or equal to}18 years were randomized 1:1 to venetoclax (800 mg oral daily) plus fulvestrant (500 mg intramuscular; Cycle 1: Days 1 and 15; subsequent 28-day cycles: Day 1) or fulvestrant alone. The primary endpoint was clinical benefit rate (CBR); secondary endpoints: progression-free survival (PFS), overall survival, and safety. Exploratory biomarker analyses included BCL2 and BCL extra-large (BCLXL) tumor expression, and PIK3CA ctDNA mutational status.
RESULTS: At primary analysis (cutoff: August 5, 2020; n = 103), venetoclax did not significantly improve CBR (venetoclax plus fulvestrant: 11.8% [n = 6/51; 95% confidence interval (CI): 4.44-23.87]; fulvestrant: 13.7% [7/51; 5.70-26.26]; risk difference -1.96% [95% CI: -16.86-12.94]). Median PFS was 2.69 months (95% CI: 1.94-3.71) with venetoclax plus fulvestrant versus 1.94 months (1.84-3.55) with fulvestrant (stratified hazard ratio 0.94 [95% CI: 0.61-1.45]; P = 0.7853). Overall survival data were not mature. A non-significant improvement of CBR and PFS was observed in patients whose tumors had strong BCL2 expression (immunohistochemistry 3+), a BCL2/BCLXL Histoscore ratio {greater than or equal to}1, or PIK3CA-wildtype status.
CONCLUSIONS: Our findings do not indicate clinical utility for venetoclax plus fulvestrant in endocrine therapy-resistant, CDK4/6 inhibitor-refractory metastatic breast tumors, but suggest possible increased dependence on BCLXL in this setting.

DOI: https://doi.org/10.1158/1078-0432.CCR-21-3811

Radiol Oncol. 2022 May 17. 56(2): 238-247

Ribociclib plus letrozole in patients with hormone receptor-positive, HER2-negative advanced breast cancer with no prior endocrine therapy: subgroup safety analysis from the phase 3b CompLEEment-1 trial.

Simona Borstnar, Marketa Palacova, Aleksandra Łacko, Constanta Timcheva, Einav Nili Gal-Yam, Konstantinos Papazisis, Juraj Beniak, Pavol Kudela, Gábor Rubovszky.

BACKGROUND: The CDK4/6 inhibitor, ribociclib in combination with endocrine therapy significantly improved progression-free survival in the first line setting in post-menopausal patients with HR+/HER2- advanced breast cancer (ABC) in a pivotal phase 3, placebo-controlled trial (MONALEESA-2) and demonstrated superior overall survival in premenopausal patients with HR+/HER2- ABC (MONALEESA-7). The multinational, phase 3b, CompLEEment-1 trial, which assessed the safety and efficacy of ribociclib plus letrozole in a broader population of patients who have not received prior endocrine therapy for advanced disease, is the largest phase 3 clinical trial to date to evaluate the safety and efficacy of a CDK4/6 inhibitor. We report a subanalysis of data from patients (N = 339) enrolled in the central and south European countries of the SERCE (Southern Europe, RUC, Central Europe) cluster of CompLEEment-1.
PATIENTS AND METHODS: Men and women of any menopausal status with HR+/HER2- ABC received once-daily oral ribociclib 600 mg (3-weeks on/1-week-off), plus letrozole 2.5 mg continuously. Men/premenopausal women also received a GnRH-agonist. The primary outcome was the number of patients with adverse events (AEs) over a timeframe of approximately 36 months. Time-to-progression, overall response rate, and clinical benefit rate were also measured.
RESULTS: Safety results in the SERCE subgroup were consistent with those in the pivotal clinical trials of ribociclib in combination with endocrine therapy. Treatment-related AEs leading to dose adjustments/interruption occurred in 63.1% of patients but led to treatment discontinuation in only 10.6%. The most common treatment-related AEs of grade ≥ 3 were neutropenia and transaminase elevations. There were no fatal treatment-related events.
CONCLUSIONS: These findings from the SERCE subgroup support the safety and manageable tolerability of ribociclib in a broad range of patients with HR+/HER2- ABC more representative of patients in real-world clinical practice.

Keywords: CDK4/6 inhibitor; CompLEEment-1 trial; HER2−; HR+; advanced breast cancer; ribociclib

DOI: https://doi.org/10.2478/raon-2022-0020

Cancer Treat Res Commun. 2022 May 06. pii: S2468-2942(22)00063-6. [Epub ahead of print]32 100573

Real-world treatment patterns and clinical outcomes in patients receiving palbociclib combinations for HR+/HER2- advanced/metastatic breast cancer in Japan: Results from the IRIS study.

Katie Mycock, Lin Zhan, Kieran Hart, Gavin Taylor-Stokes, Gary Milligan, Christian Atkinson, Debanjali Mitra.

BACKGROUND: The incidence of breast cancer is rising in Japan, particularly in postmenopausal women. The CDK 4/6 inhibitor palbociclib has demonstrated efficacy in clinical studies in patients with hormone receptor-positive (HR+), human epidermal growth factor 2 (HER2)-negative advanced/metastatic breast cancer (ABC/MBC). The Ibrance Real World Insights (IRIS) study (NCT03159195) collected real-world data for palbociclib-treated patients in several countries including Japan, where such data are currently scarce.
METHODS: IRIS was a retrospective chart review study of patients with confirmed HR+/HER2- ABC/MBC receiving palbociclib according to approved indications in real-world clinical practice. In Japan, physicians each abstracted data from patient medical records for up to eight sequential patients treated with palbociclib plus an aromatase inhibitor (P+AI) or fulvestrant (P+F). Outcomes included progression-free rates (PFRs) and survival rates (SRs).
RESULTS: Fifty-eight physicians abstracted data for 170 patients receiving palbociclib in the first (64.1%) or second or later line (35.9%), in combination with AI (51.2%) or fulvestrant (48.8%). Median follow-up was 10.4 months. Most patients were initiated on palbociclib 125 mg/d (P+AI, 63.2%; P+F, 78.3%). PFRs at 12 and 24 months were 76.2% and 52.6%, respectively, for P+AI and 71.6% and 65.6%, respectively for P+F. PFRs at 12 and 24 months were 85.4% and 66.5%, respectively, for first-line palbociclib combinations and 56.4% and 50.7%, respectively, for second- or later-line palbociclib combinations.
CONCLUSIONS: In this analysis of the Japanese IRIS cohort, outcomes in terms of PFRs and SRs appear to be better with first- versus second or later-line palbociclib, regardless of the endocrine partner.

Keywords: Japan; Metastatic breast cancer; Palbociclib; Real-world; Retrospective study

DOI: https://doi.org/10.1016/j.ctarc.2022.100573

Gan To Kagaku Ryoho. 2022 May;49(5): 581-583

[A Case of Postoperative Pulmonary Metastasis of Breast Cancer with Complete Response by Abemaciclib plus Fulvestrant Therapy].

Takayuki Higashi, Koichiro Ozawa, Saki Takei, Shinya Takagi, Moriyoshi Yokoyama, Kenji Mase, Toshiyuki Moriya, Akiko Takeshita, Masaomi Mizutani.

A 66-year-old woman underwent total mastectomy with level Ⅰ and Ⅱ axillary lymph node dissection for right breast cancer in July 2007. The pathology results indicated the presence of T2N0M0 invasive ductal carcinoma(tubule forming type), that was estrogen receptor-positive and human epidermal growth factor 2-negative. She received postoperative adjuvant therapy with oral anastrozole(ANA)for 5 years. Eleven years after surgery, at the age of 77 years, a chest X-ray examination during a routine health checkup identified a mass shadow in the right lung. Further investigation revealed bilateral multiple lung metastases due to breast cancer recurrence. Histological examination of a tissue obtained by computed tomography(CT)-guided lung biopsy confirmed that the histological type and subtype were identical to those found in the initial surgery. Hence, endocrine therapy with ANA plus CDK4/6 inhibitor was started in November 2018. However, the first CDK4/6 inhibitor, palbociclib, caused severe myelosuppression even when the dose was reduced by 2 levels. Therefore in January 2019, the patient was switched to abemaciclib, with the dose reduced by 1 level initially and then reduced by 2 levels from August 2019. In June 2019, new multiple lung metastases appeared, and the patient was switched from ANA to fulvestrant, after which complete response was achieved in 6 months. CT in June 2021 showed no recurrence, and the patient(now 80-year-old)continues to take abemaciclib plus fulvestrant therapy.