Abstract 1746P
Background
LEN is approved for RR-DTC at a starting dose of LEN 24 mg/d (LEN24). In the phase 2 Study 211, a starting dose of LEN 18 mg/d (LEN18) did not show noninferiority vs LEN24 for objective response rate at week (wk) 24; safety as of wk 24 was similar in both arms. We report the impact of LEN treatment on HRQoL, a secondary objective of Study 211.
Methods
Pts with RR-DTC were randomly assigned to a starting dose of LEN18 (n = 77) or LEN24 (n = 75). HRQoL was assessed at baseline, every 8 wks until wk 24, then every 16 wks, and at the off-treatment visit, using EQ5D and FACT-G instruments. Mean change from baseline scores and times to first and definitive deterioration were evaluated. Minimally important difference (MID) thresholds herein were 0.08 points for the health utilities index (HUI), and 7 points for the visual analog scale (VAS) and FACT-G. Analyses for any individual HRQoL outcome included all pts with valid data for that outcome. All statistics are nominal and descriptive.
Results
Baseline EQ5D, FACT-G scores, and overall changes from baseline (mean follow-up: 33 wks) were comparable across treatment arms (Table). No significant differences in median time to first deterioration (wks) were seen with LEN18 vs LEN24 across instruments (EQ5D-VAS, 21.9 vs 16.3, HR 0.92 [95% CI 0.61–1.39]; EQ5D-HUI, 28.1 vs 16.0, HR 0.66 [95% CI 0.43–1.02]; FACT-G 7 points MID, 24.0 vs 16.1, HR 0.80 [95% CI 0.53–1.22]). Similar results were seen for median time to definitive deterioration (wks) (EQ5D-VAS, 72.1 vs 88.7, HR 1.58 [95% CI 0.92–2.70]; EQ5D-HUI, 73.9 vs 71.4, HR 0.89 [95% CI 0.53–1.49]; FACT-G 7 points MID, 72.4 vs 88.1, HR 0.78 [95% CI 0.46–1.30]). Table: 1746P
| Overall HRQoL | |||
| Scale | Least Squares Mean ChangeFrom Baseline (standard error) | Least Squares Mean Difference (95% CI); P-value | |
| LEN18 | LEN24 | LEN18 vs LEN24 | |
| EQ5D | |||
| EQ-VAS | −5.68 (1.619) | −5.25 (1.601) | −0.42 (−4.88 to 4.03); 0.8507 |
| HUI | −0.08 (0.018) | −0.06 (0.017) | −0.02 (−0.07 to 0.03); 0.4586 |
| FACT-G | |||
| Total score | −4.14 (1.438) | −4.61 (1.397) | 0.47 (−3.45 to 4.39); 0.8132 |
| Physical well-being | −3.13 (0.518) | −3.61 (0.510) | 0.48 (−0.95 to 1.92); 0.5058 |
| Social/family well-being | −0.07 (0.525) | 0.03 (0.518) | −0.10 (−1.54 to 1.34); 0.8886 |
| Emotional well-being | 0.91 (0.323) | 0.34 (0.319) | 0.57 (−0.32 to 1.46); 0.2076 |
| Functional well-being | −1.56 (0.531) | −1.28 (0.529) | −0.28 (−1.74 to 1.19); 0.7076 |
Conclusions
In RR-DTC, HRQoL for pts in the LEN18 arm was not statistically different from pts in the LEN24 arm. These data combined with prior efficacy data support use of the LEN24 starting dose in pts with RR-DTC..
Clinical trial identification
NCT02702388.
Editorial acknowledgement
Medical writing support was provided by Heather A. Mitchell, PhD, of Oxford PharmaGenesis Inc., Newtown, PA, USA, and was funded by Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
M.H. Taylor: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Eisai Inc.; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Sanofi/Genzyme; Financial Interests, Personal, Advisory Board: Array Biopharma; Financial Interests, Personal, Advisory Board: LOXO Oncology; Financial Interests, Personal, Advisory Board: Blueprint Medicines; Financial Interests, Personal, Advisory Board: Arqule; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: Eisai Inc.; Financial Interests, Institutional, Funding: BMS; Financial Interests, Institutional, Funding: Merck Sharp & Dohme Corp; Financial Interests, Institutional, Funding: Pharmacyclics; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Eisai Inc.; Financial Interests, Institutional, Funding: Incyte; Financial Interests, Institutional, Funding: EMD Serono; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Seattle Genetics; Financial Interests, Institutional, Funding: AbbVie; Financial Interests, Institutional, Funding: Genentech; Financial Interests, Institutional, Funding: Eli Lilly; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Acerta Pharma; Financial Interests, Institutional, Funding: Genzyme Corp.; Financial Interests, Institutional, Funding: Pfizer. S. Leboulleux: Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Sanofi Genzyme. B. Konda: Financial Interests, Institutional, Funding: Eisai Inc.; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: BMS; Financial Interests, Institutional, Funding: Xencor; Financial Interests, Institutional, Funding: Eli Lilly & Co. C. de la Fouchardiere: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Pierre Fabre Oncologie; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Servier; Non-Financial Interests, Institutional, Other, Coordinating PI: Pierre Fabre Oncologie; Non-Financial Interests, Institutional, Other, Coordinating PI: Servier. B.G.M. Hughes: Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Takeda. A.G. Gianoukakis: Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Blueprint Medicine. I. Romanov: Financial Interests, Personal, Other, Honoraria: Eisai; Financial Interests, Personal, Other, Honoraria: Merck Serono; Financial Interests, Personal, Other, Honoraria: BMS. M.K. Krzyzanowska: Financial Interests, Institutional, Funding: Eisai; Financial Interests, Institutional, Funding: Exelixis; Financial Interests, Institutional, Funding: Ipsen. D. Garbinsky: Other, Personal and Institutional, Full or part-time Employment: RTI Health Solutions. B. Sherif: Other, Personal and Institutional, Full or part-time Employment: RTI Health Solutions. J.J. Pan: Other, Personal and Institutional, Full or part-time Employment: Eisai Inc. T.A. Binder: Financial Interests, Personal, Stocks/Shares: Amgen; Other, Personal and Institutional, Full or part-time Employment: Eisai Inc. N. Sauter: Other, Personal and Institutional, Full or part-time Employment: Eisai Inc. R. Xie: Other, Personal and Institutional, Full or part-time Employment: Eisai Inc. M.S. Brose: Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Personal, Other, Honoraria & Consulting Fees: Eisai; Financial Interests, Personal, Other, Honoraria & Consulting Fees: Bayer; Financial Interests, Personal, Other, Honoraria & Consulting Fees: Lilly; Financial Interests, Personal, Other, Honoraria & Consulting Fees: Loxo ; Financial Interests, Personal, Other, Honoraria & Consulting Fees: Blueprint Medicines. All other authors have declared no conflicts of interest.