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
2860 - Prognostic value of metabolic response assessed by 18FDG-PET after induction chemotherapy and after chemoradiotherapy (CRT) in localized esophageal squamous cell carcinoma (ESCC) patients (pts) receiving definite CRT (dCRT)
Presenter: Yeonghak Bang
Session: Poster Display session 2
Resources:
Abstract
3881 - Comprehensive genomic profiling of early-stage esophageal squamous cell carcinoma
Presenter: Jing Zuo
Session: Poster Display session 2
Resources:
Abstract
3944 - A novel nomogram and risk classification system predicting radiation pneumonitis in patients with esophageal cancer receiving radiotherapy
Presenter: Lu Wang
Session: Poster Display session 2
Resources:
Abstract
1956 - Drinking alcohol, smoking, multiple dysplastic lesions and the risk of field cancerization of squamous cell carcinoma in the esophagus and head and neck region
Presenter: Chikatoshi Katada
Session: Poster Display session 2
Resources:
Abstract
2144 - Neoadjuvant chemotherapy can eliminate the negative impact of postoperative infectious complications on recurrence in patients with esophageal cancer
Presenter: Kazuki Kano
Session: Poster Display session 2
Resources:
Abstract
2403 - Comparison of chemoradiotherapy (CRT) followed by consolidation with cisplatin and 5-fluorouracil (CF) versus definitive CRT with carboplatin and paclitaxel (CP) in esophageal cancer
Presenter: Marcelle Cesca
Session: Poster Display session 2
Resources:
Abstract
3247 - Paclitaxel in Combination with Cisplatin and 5-fluorouracil(TPF) Induction Chemotherapy for Locally Advanced Borderline-resectable Esophageal Squamous cell Carcinoma: A Phase II Clinical Trial
Presenter: Yuhong Li
Session: Poster Display session 2
Resources:
Abstract
4293 - Prognosis of esophageal squamous cell carcinoma based on local immunity evaluation
Presenter: Elena Zlatnik
Session: Poster Display session 2
Resources:
Abstract
5419 - Impact of Sarcopenia and adiposity in survival of metastatic esophageal cancer (MEC)
Presenter: Aline Fares
Session: Poster Display session 2
Resources:
Abstract
2083 - PALAESTRA - A phase II trial with short-course radiotherapy followed by chemotherapy as palliative treatment in esophageal adenocarcinoma
Presenter: David Borg
Session: Poster Display session 2
Resources:
Abstract