IntroductionStudies have shown that, at low doses and with careful titration, combination therapy with intrathecal ziconotide and morphine results in rapid control of opioid-refractory cancer pain. However, there is a lack of published data regarding the efficacy and safety of intrathecal ziconotide specifically for the treatment of neuropathic cancer pain.Case seriesCase reports of ziconotide intrathecal infusion in eight patients (age 45–71 years; 75% male) with chronic, uncontrolled cancer pain during therapy with intrathecal morphine plus bupivacaine were reviewed. Neuropathic pain was confirmed in five patients. Treatment was initiated with adjunctive ziconotide when pain ≥5 on a visual analog scale persisted in spite of 3 successive 20% dose increases of intrathecal morphine. Ziconotide was initiated at 0.5–1.0 µg/day, with mean increases of 0.5 µg every 4–7 days if required (maximum dose 10 µg/day; mean dose 4.9 µg/day). Pain intensity was reduced in all patients after 3–5 days. Of the eight patients, three died for reasons unrelated to ziconotide, three discontinued treatment due to adverse effects (predominantly psychoneurological disorders), and one patient is still receiving treatment. One patient discontinued ziconotide due to confusion and delirium. Due to continued lack of pain control with intrathecal morphine, intrathecal fentanyl was initiated; however, effective pain relief was not achieved with 1500 µg/day. Ziconotide was restarted and the patient then achieved pain control.ConclusionOn the basis of our clinical experience, we recommend adding ziconotide to intrathecal opioid-based therapy in cancer patients with neuropathic pain inadequately controlled by intrathecal morphine alone.FundingEisai, Spain.Electronic supplementary materialThe online version of this article (doi:10.1007/s40120-015-0035-z) contains supplementary material, which is available to authorized users.
Introduction and objectives: Cyclin dependent kinase (CDK) 4/6 inhibitors along with endocrine therapy (ET) is the standard first-line for endocrine receptor (ER)-positive HER2-negative metastatic breast cancer. Three CDK 4/6 inhibitors have the FDA and EMA approval: abemaciclib, palbociclib and ribociclib. They appear to have notable differences in their pharmacokinetic characteristics and ability to inhibit every cyclin. Nevertheless, the natural history of disease associated with each CDK 4/6 inhibitor remains unclear. The aim of this study is to establish a risk prediction model for disease progression under the different therapeutic regimes and assess whether there are differences in terms of efficacy between them. Methods: This is a retrospective observational study in which patients treated with ET plus abemaciclib, palbociclib or ribociclib as front line for metastatic breast cancer in Virgen del Rocio Hospital between April 2014 and April 2021 were selected. Patients in this population were followed for a period of 36 months. They were studied according to their clinical characteristics and disease outcome using descriptive analysis. The risk of progression was studied by a transversal method using a univariate logistic regression model. Moreover, Kaplan Meier curves were used to estimate progression-free survival (PFS) and the Breslow test to estimate the p value. All statistical analyses were performed with SPSS 28.0 (Statistical Package for the Social Sciences). Results: A total of 189 patients were selected. 55(29.1%) of them received abemaciclib, 83(44%) palbociclib and 51(27%) ribociclib. 50(27%) patients had de novo metastatic disease, while 139(73%) were recurrences of previous disease. Almost half of the patients (45%) received fulvestrant and 104 (55%) patients received aromatase inhibitors. Table 1 represents the proportion of patients with visceral involvement and endocrine resistance in each arm. The univariate logistic regression model showed that patients treated with palbociclib had 2.36(CI95% 1.165-4.765) times the risk of progression compared to abemaciclib, while patients treated with ribociclib had 2.50(CI95% 1.139-5. 475) times the risk of progression compared to abemaciclib. Overall PFS was 30.03 months. A tendency towards best PFS with abemaciclib in comparison with the other CDK 4/6 inhibitors was appreciated, but it did not reach statistical significance (abemaciclib-palbociclib p=0.289; abemaciclib-ribociclib; p= 0.293; palbociclib-ribociclib p=0.979). Conclusions: In our sample of patients with ER-positive HER2-negative metastatic breast cancer treated with the different CDK 4/6 inhibitors as front line therapy, patients with abemaciclib achieved a lower risk of progression and a trend toward longer PFS. Further follow-up will be necessary to determine whether abemaciclib provides greater benefit in PFS. Table 1. Proportion of patients with visceral involvement and endocrine resistance in each arm. Visceral metastases: Liver, Lung, central nervous System; Non-Visceral: Bone, skin, Lymph node. Citation Format: Mónica Cejuela, M. ángeles Castilla, Marta Benavent, Sonia Molina-Pinelo, Maria A Dominguez-Cejudo, Ana Gil, Alejandro Falcon, Francisco Javier Salvador Bofill. Palbociclib, ribociclib and abemaciclib in real-world data: risk of disease progression on first-line treatment of metastatic breast cancer. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-01-13.
e13015 Background: Novel HER2 antibody-drug conjugates have demonstrated clinical benefit in breast cancer with HER2 IHC scores 1+ or 2+/ISH negative. As a result, a new concept of HER2 low breast cancer has been proposed. The prognostic implications of this expression remain unclear. To determine whether HER2 low expression affects disease evolution in patients with endocrine receptor positive, HER2 negative breast cancer, we performed a retrospective analysis of patients treated with first line CDK4/6 inhibitors in our center. Methods: We conducted a search for patients who received first line CDK4/6 inhibitors plus endocrine therapy at Virgen del Rocio Hospital between June 2016 and September 2021. 175 subjects were selected and followed for 42 months. Patients were grouped according to HER2 expression: HER2 0+ and HER2 low (IHC 1+ or 2+/ISH negative). Clinical characteristics and PFS were then compared. Clinical characteristics were evaluated by descriptive analysis. Kaplan Meier curves were used to estimate PFS, and Breslow test to estimate p-value. Statistical analyses were performed with SPSS 28.0. Results: All patients were female and median age at treatment initiation was 61 years. 49 patients received abemaciclib, 83 palbociclib and 43 ribociclib. 49 patients were HER2 0+, 57 HER2 1+ and 69 HER2 2+. Key clinical and treatment characteristics are shown. Overall PFS was 35.61 months (95% CI 25.46 - 45.76). PFS was 21.52 months (95% CI: 14.30 - 28.73), 31.15 months (95% CI: 15.59 - 46.70) and 39.49 months (95% CI: not estimable) in the HER2 0+, 1+ and 2+ population, respectively. There was no difference between the three arms: HER2 0+ vs HER2 1+ p=0.881; HER2 0+ vs HER2 2+ p=0.155; HER2 1+ vs HER2 2+ p=0.238. No significant differences were observed when comparing the HER2 0+ cohort to the overall HER2 low population: p=0.347. Conclusions: In our cohort of patients with luminal phenotype breast cancer treated with CDK4/6 inhibitors, HER2 low expression was associated with a trend toward longer PFS, although no statistically significant differences were found. [Table: see text]
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