Abstract 2767
Background
CELESTIAL (NCT01908426), a phase 3 study in patients with aHCC who progressed on sorafenib (≤2 previous systemic treatments allowed), demonstrated improved survival and progression-free survival with cabozantinib over placebo. CELESTIAL was stopped early for benefit at the second interim analysis (hazard ratio for death in overall population, 0.76 [95% confidence interval 0.63–0.92; p = 0.005] resulting in short follow-up for some patients). This retrospective analysis compared patient experience of three discrete health states in patients receiving second-line cabozantinib vs placebo in CELESTIAL: time with grade 3/4 toxicity before progression (TOX); time without grade 3/4 toxicity before progression (TWiST); and survival time after progression or relapse (REL).
Methods
Overall, 495 patients in CELESTIAL had sorafenib as the only prior therapy (cabozantinib, 331; placebo, 164). For each patient, times spent in TOX, TWiST and REL were calculated. Toxicities were based on reported adverse events. Patients censored prior to progression or death (32%) accrued time in each health state up to that date.
Results
Second-line cabozantinib was associated with significantly longer mean TOX (49.8 vs 9.8 days, p < 0.0001), and also TWiST (110.9 vs 78.1 days, p = 0.001) than placebo; survival times after progression (REL) were similar; (Table). Analyses based on all patients in CELESTIAL (N = 707) or limited to those with ≥100 days of follow-up (regardless of whether they had a progression event prior to that time) resulted in numerically different estimates for each health state, but no qualitative differences in findings.Table:
754P
Health state | Cabozantinib (N = 331) Mean days (95% CI) | Placebo (N = 164) Mean days (95% CI) | Difference cabozantinib - placebo Mean days (95% CI; t test) |
---|---|---|---|
TOX | 49.8 (39.2–60.3) | 9.8 (2.6–17.0) | 40.0 (27.3–52.7; p < 0.0001) |
TWiST | 110.9 (96.7–125.2) | 78.1 (64.7–91.5) | 32.8 (13.3–52.3; p = 0.001) |
REL | 174.5 (152.5–196.5) | 178.6 (144.1–213.0) | -4.1 (-43.5–35.4; p = 0.85) |
CI, confidence interval; REL, survival time after progression/relapse; TOX, time with a grade 3/4 toxicity before progression; TWiST, time without disease symptoms and grade 3/4 toxicity
Conclusions
Patients with aHCC receiving second-line cabozantinib after sorafenib spent significantly more time without disease symptoms and toxicity than those receiving placebo, despite an increase in days with grade 3/4 toxicity before progression.
Clinical trial identification
NCT01908426.
Editorial acknowledgement
Oxford PharmaGenesis, Oxford, UK for providing editorial support, which was sponsored by Ipsen, Abingdon, UK in accordance with Good Publication Practice guidelines.
Legal entity responsible for the study
Ipsen.
Funding
Ipsen.
Disclosure
N. Freemantle: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Takeda; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Biogen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Yesaro; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Allergan; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: PTC; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca. G.K. Abou-Alfa: Advisory / Consultancy: 3DMedcare; Advisory / Consultancy, Research grant / Funding (institution): Agions; Advisory / Consultancy: Alignmed; Advisory / Consultancy: Antengene; Advisory / Consultancy: Aptus; Advisory / Consultancy: Aslan; Advisory / Consultancy: Astellas; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Beigene; Advisory / Consultancy: Bioline; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: Boston Scientific; Advisory / Consultancy: Bridgebio; Advisory / Consultancy: Carsgen; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy, Research grant / Funding (institution): Casi; Advisory / Consultancy: Cipla; Advisory / Consultancy: Cytom X; Advisory / Consultancy: Daiichi. A. Cheng: Honoraria (self): Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eisai; Honoraria (self): Merck Sharp Dohme; Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ono Pharmaceutical; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: IQVIA; Advisory / Consultancy: Bayer Schering Pharma; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Nucleix Ltd.; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer Yakuhin, Ltd; Speaker Bureau / Expert testimony: Amgen Taiwan. R.K. Kelley: Advisory / Consultancy: Genentech/ Roche; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Agios; Advisory / Consultancy, Research grant / Funding (institution): BMS; Research grant / Funding (institution): Adaptimmune; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): QED; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Medimmune; Research grant / Funding (institution): Taiho. V. Valcheva: Full / Part-time employment: Ipsen. F. Benzaghou: Full / Part-time employment: Ipsen. P. Mollon: Full / Part-time employment: Ipsen.
Resources from the same session
1058 - Assessment of CPS+EG, Neo-Bioscore and modified Neo-Bioscore in breast cancer patients treated with preoperative systemic therapy: a multicenter cohort study
Presenter: LING XU
Session: Poster Display session 2
Resources:
Abstract
1156 - The concordance of treatment decision guided by Oncotype and the PREDICT tool in early stage breast cancer
Presenter: Hadar Goldvaser
Session: Poster Display session 2
Resources:
Abstract
3447 - Influence of first treatment delay on survival among breast cancer subtypes
Presenter: Irene Zarcos Pedrinaci
Session: Poster Display session 2
Resources:
Abstract
3505 - Clinical features of early-stage (I-III) triple-negative breast cancer (TNBC) patients with tumors exhibiting low-overall change in molecular profile after neoadjuvant therapy.
Presenter: Nour Abuhadra
Session: Poster Display session 2
Resources:
Abstract
5442 - Meta-analysis in HER2+ early breast cancer therapies and cost-effectiveness in a Brazilian perspective
Presenter: Marcos Magalhaes
Session: Poster Display session 2
Resources:
Abstract
1570 - Anti-mullerian hormone (AMH) levels and antral follicle counts (AFC) may predict ovarian reserves before systemic chemotherapy (SC) in women with breast cancer(BC); a prospective clinical study
Presenter: Cetin Ordu
Session: Poster Display session 2
Resources:
Abstract
2698 - Prognosis of selected triple negative apocrine breast cancer patients who did not receive adjuvant chemotherapy.
Presenter: Giuseppe Cancello
Session: Poster Display session 2
Resources:
Abstract
3104 - Novel Blood Based Circulating Tumor Cell Biomarker For Breast Cancer Detection
Presenter: Chun-Yu Liu
Session: Poster Display session 2
Resources:
Abstract
4631 - Multi-Gene Prognostic Signatures and Prediction of Pathological Complete Response of ER-Positive HER2-Negative Breast Cancer Patients to Neo-Adjuvant Chemotherapy
Presenter: Claudia Mazo
Session: Poster Display session 2
Resources:
Abstract
4632 - Impact of menopause status on breast cancer outcomes and amenorrhea incidence during adjuvant tailored dose dense chemotherapy
Presenter: Andri Papakonstantinou
Session: Poster Display session 2
Resources:
Abstract