Abstract 2777
Background
Abemaciclib, a selective CDK4 & 6 inhibitor, demonstrated single-agent activity in NSCLC and melanoma (Patnaik et al., 2016). Clinical data demonstrate abemaciclib penetrates the blood brain barrier resulting in comparable concentrations in tissues and plasma (Sahebjam et al., 2016).
Methods
Study JPBO is a Simon 2-stage trial evaluating abemaciclib in 6 pt cohorts with BM secondary to HR+ breast cancer, NSCLC, or melanoma. Here, we report NSCLC and melanoma cohorts. Pts with ≥1 new or not previously irradiated BM ≥ 10mm or a progressive BM previously irradiated were eligible. Abemaciclib was orally administered BID on a continuous dosing schedule. Primary endpoint was objective intracranial response rate (OIRR; [confirmed CR+PR]) based on Response Assessment in Neuro-Oncology BM response assessment criteria (RANO-BM). Secondary endpoints included intracranial clinical benefit rate, PFS, OS, and safety.
Results
28 (NSCLC) and 23 (MEL) pts were enrolled and 23 (NSCLC) and 22 (MEL) were evaluable. Pts had a median of 2 prior systemic therapies in the metastatic setting. 35% (NSCLC) and 46% (MEL) of pts had prior whole brain radiotherapy. 35% (NSCLC) and 27% (MEL) pts had stereotactic radiotherapy. Median time from radiation to study enrollment was 4.8 (NSCLC) to 5.6 (MEL) months. No confirmed intracranial response was observed (OIRR 0% for both cohorts). 21.7% (NSCLC) and 13.6% (MEL) of pts showed a decrease in the sum of their intracranial target lesions. ICBR (CR+PR+SD persisting for > 6 months) was 26.1% (NSCLC) and 9.1% (MEL). Median PFS was 1.5 months (95% CI, 1.4-2.8) for NSCLC and 1.2 months (95% CI, 1.0-1.6) for MEL. Median OS was 7.1 months (95% CI, 3.7-9.4) for NSCLC and 2.9 months (95% CI, 1.2-4.3) for MEL. Based on efficacy results, enrollment closed at end of stage 1. Safety and tolerability were similar as previously reported for abemaciclib.
Conclusions
There was limited intracranial clinical activity for abemaciclib monotherapy in NSCLC and MEL pts in this study; OIRR and short median PFS suggest that no further studies for abemaciclib monotherapy are warranted in this pt population.
Clinical trial identification
NCT02308020.
Editorial acknowledgement
Medical writing assistance was provided by Kristi Gruver, employee of Eli Lilly and Company.
Legal entity responsible for the study
Eli Lilly and Company.
Funding
Eli Lilly and Company.
Disclosure
E. Le Rhun: Advisory / Consultancy, Research grant / Funding (institution), Oscar Lambert Center, Lille, FR: Mundipharma; Research grant / Funding (institution), University Hospital, Lille, FR: Amgen; Advisory / Consultancy, personal fees: Novartis; Advisory / Consultancy, personal fees: Daiichi Sankyo; Advisory / Consultancy, personal fees: Abbvie. G. Jerusalem: Advisory / Consultancy, Non-remunerated activity/ies, per patient investigator fee: Eli Lilly and Company; Research grant / Funding (self), Non-remunerated activity/ies, personal fees: Novartis; Research grant / Funding (self), Non-remunerated activity/ies, personal fees: Roche; Advisory / Consultancy, Non-remunerated activity/ies, personal fees: Pfizer; Advisory / Consultancy, personal fees: Celgene; Advisory / Consultancy, Non-remunerated activity/ies, personal fees: Amgen; Advisory / Consultancy, Non-remunerated activity/ies, personal fees: BMS; Advisory / Consultancy, personal fees: Puma Technology; Advisory / Consultancy, Non-remunerated activity/ies, personal fees: AstraZeneca; Advisory / Consultancy, personal fees: Daiichi Sankyo; Advisory / Consultancy, personal fees: Abbvie. D. Subramaniam: Advisory / Consultancy, personal fees: AstraZeneca; Advisory / Consultancy, personal fees: Takeda Oncology; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Genentech. Y. Chen: Shareholder / Stockholder / Stock options, Full / Part-time employment, employee and stock options: Eli Lilly and Company. P.F. Conte: Research grant / Funding (self): Novartis; Travel / Accommodation / Expenses, travel grant: Eli Lilly and Company; Research grant / Funding (self): Roche; Research grant / Funding (self): AstraZeneca; Travel / Accommodation / Expenses, travel grant: Celgene; Travel / Accommodation / Expenses, travel grant: Tesaro. All other authors have declared no conflicts of interest.
Resources from the same session
1309 - Quantifying the Effects of the Korean National Cancer Screening Program on Cervical Cancer Mortality
Presenter: Nhung Bui
Session: Poster Display session 2
Resources:
Abstract
1346 - Spread of tumor and adverse events after modified radical hysterectomy for FIGO Stage IB1 cervical cancer patients with tumor diameter preoperatively estimated 2 cm or less: Japan Clinical Oncology Group trial (JCOG1101); exploratory analysis before primary analysis.
Presenter: Takahide Arimoto
Session: Poster Display session 2
Resources:
Abstract
5352 - Impact of Combined Interstitial and Intracavitary Brachytherapy in locally advanced Cervical cancer: A Survival and toxicity profile assessment
Presenter: Vibhay Pareek
Session: Poster Display session 2
Resources:
Abstract
2049 - Chemoradiotherapy response prediction model by proteomic expressional profiling in patients with locally advanced cervical cancer
Presenter: Chel Hun Choi
Session: Poster Display session 2
Resources:
Abstract
1923 - Disparities starting adjuvant chemotherapy for locally advanced cervix cancer in the international, academic, randomised, phase 3 OUTBACK trial (ANZGOG 0902, RTOG 1174, NRG 0274)
Presenter: Linda Mileshkin
Session: Poster Display session 2
Resources:
Abstract
3284 - Primary results from CECILIA, a global single-arm phase 2 study evaluating bevacizumab (BEV), carboplatin (C) and paclitaxel (P) for advanced cervical cancer (aCC)
Presenter: Andres Redondo
Session: Poster Display session 2
Resources:
Abstract
843 - Prognostic and clinicopathological significance of PD-L1 in patients with cervical cancer: a meta-analysis
Presenter: Xiaobin Gu
Session: Poster Display session 2
Resources:
Abstract
1020 - Clinical impact of molecular profiling of cervical cancer (CC) patients (pts) in a dedicated Phase I (P1) unit
Presenter: Mariana Scaranti
Session: Poster Display session 2
Resources:
Abstract
872 - Comparative proteomic profiles of cervical cancer and paried paracancerous tissue and the potential effects of DUSP7 over-expression through inhibiting RAS pathway on the biological characteristics of human cervical cancer cell line SIHA
Presenter: Xuan Jiang
Session: Poster Display session 2
Resources:
Abstract
1988 - Molecular profiling reveals novel targetable biomarkers in neuroendocrine carcinoma of the uterine cervix
Presenter: Semir Vranic
Session: Poster Display session 2
Resources:
Abstract