Abstract 168P
Background
The phase 3 REFLECT trial showed that LEN was noninferior to sorafenib in OS among pts with uHCC. ORR with LEN was 41%. We characterize pts enrolled in REFLECT who were treated with 1L LEN and experienced complete response (CR), near-CR (nCR; partial response [PR] with target lesion reduction [TLR] ≥ 75%) or PR with other TLR.
Methods
Pts who received LEN (bodyweight (BW) ≥ 60 kg: 12 mg/d; BW < 60 kg: 8 mg/d) and were responders (CR/PR) were included in this analysis. Tumor responses were assessed per independent imaging review by mRECIST. Responders were grouped by tumor reduction including CR, nCR (TLR ≥ 75%), PR with TLR ≥ 50-< 75% or ≥ 30-< 50%. Baseline demographics/disease characteristics were summarized by group. Median (m)OS and duration of response (DOR) were calculated using the Kaplan-Meier method; 95% CIs were estimated with a generalized Brookmeyer and Crowley method.
Results
Of the 478 pts with uHCC randomized to LEN, 194 pts had an objective response and were included in this analysis; 10 pts had a CR and 184 pts had a PR (nCR, n=49; PR-TLR ≥ 50-< 75%, n=72; PR-TLR ≥ 30-< 50%, n=63). Baseline demographics/characteristics were generally well balanced. mDOR was 20.3 mos for pts with CR, 7.7 mos for pts with nCR, 7.3 mos for pts with PR-TLR ≥ 50-< 75%, and 3.7 mos for pts with PR-TLR ≥ 30-< 50% (Table). Proportions of pts with DOR ≥ 6, 12, and 18 mos were generally higher in pts with CR and nCR vs pts with PR-TLR ≥ 50-< 75% and PR-TLR ≥ 30-< 50%. mOS was similar for pts with CR (25.4 mos) and nCR (23.4 mos), and higher vs other PR groups. Table: 168P
| CR (n=10) | Near-CR (PR with TLR ≥ 75%) (n=49) | PR with TLR ≥ 50–< 75% (n=72) | PR with TLR ≥ 30–< 50% (n=63) | |
| Median DOR, mos (95% CI) | 20.3 (4.7–NE) | 7.7 (6.9–9.2) | 7.3 (5.5–7.4) | 3.7 (3.7–5.6) |
| Pts with DOR ≥ 6/≥ 12/≥ 18 mos, % | 70/40/30 | 57/12/10 | 43/17/8 | 17/3/2 |
| Median OS, mos (95% CI) | 25.4 (5.5–NE) | 23.4 (12.0–30.1) | 19.8 (14.1–23.1) | 14.4 (13.1–19.1) |
| OS rate 12 mos, % (95% CI) | 80 (41–95) | 63 (48–75) | 71 (59–80) | 67 (54–77) |
| OS rate 24 mos, % (95% CI) | 60 (25–83) | 48 (33–61) | 37 (26–49) | 30 (19–42) |
Conclusions
To our knowledge, this is the first study characterizing pts with uHCC who experienced a nCR and looking at outcomes by depth of responses. Responses were durable, irrespective of TLR. Despite the small sample size for pts with CR (n=10), it was notable that mOS was similar between pts with CR and nCR, indicating that a deeper tumor response may be associated with survival. These results further support LEN as a standard-of-care 1L treatment.
Clinical trial identification
NCT01761266.
Editorial acknowledgement
Medical writing support was provided by Oxford PharmaGenesis Inc., Newtown, PA, USA.
Legal entity responsible for the study
Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Funding
Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Disclosure
A. Mahipal: Financial Interests, Personal, Advisory Role: AstraZeneca/MedImmune, Taiho Oncology, Guardant Health, Elevar Therapeutics; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Taiho Oncology; Financial Interests, Personal, Research Grant: Taiho. A. Cheng: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Bayer Healthcare, AstraZeneca, Genentech/Roche, Merck Sharp Dohme, BeiGene, Ltd., Exelixis Ltd., Ipsen Innovation, F. Hoffmann-La Roche Ltd., Omega Therapeutics, Inc.; Financial Interests, Personal, Invited Speaker: Eisai, Ono Pharmaceutical, Bayer Yakuhin Ltd., Novartis, Amgen Taiwan, Chugai Pharmaceutical; Financial Interests, Personal, Other, Travel: IQVIA; Financial Interests, Personal, Expert Testimony: AbbVie Inc. M. Kudo: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Eli Lilly, Takeda, AstraZeneca; Financial Interests, Personal, Advisory Board: Roche, Chugai, Eisai, AstraZeneca; Financial Interests, Institutional, Research Grant: Otsuka, Taiho, Eisai, AbbVie, GE Healthcare, Chugai. A. Burgoyne: Financial Interests, Personal, Advisory Role: Exelixis, Deciphera, Genentech/Roche, Kuur Therapeutics, Clinical Care Options; Financial Interests, Personal, Speaker’s Bureau: Deciphera, AstraZeneca. A. Kalyan: Financial Interests, Personal, Advisory Board, Consulting and advisory board: AstraZeneca; Financial Interests, Personal, Advisory Board, Consulting and Advisory Board: Genentech; Financial Interests, Personal, Invited Speaker, Speaking for Nurses and Doctors: Genentech; Financial Interests, Personal, Advisory Board: Exelixis, Boston Scientific; Financial Interests, Personal, Other, Consulting: Boston Scientific; Financial Interests, Institutional, Invited Speaker: Boston Scientific, Exelixis; Non-Financial Interests, Principal Investigator, Investigator: Exelixis; Non-Financial Interests, Principal Investigator: Boston Scientific. R. Lencioni: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca. C. Lopez: Financial Interests, Personal, Invited Speaker: Ipsen, Roche, Eisai, Novartis, Pfizer, AAA, Bayer, Lilly, Amgen, Merck, AstraZeneca, Servier, Roche, Ipsen, Eisai; Financial Interests, Personal, Advisory Board: Ipsen, Roche, Eisai, Pfizer, Bayer, Lilly, Amgen, Merck, AstraZeneca, Servier; Financial Interests, Personal, Funding: Roche, Pfizer, Novartis, Bayer, Lilly, Eisai; Financial Interests, Personal and Institutional, Research Grant: Amgen, AstraZeneca, Servier. B. Daniele: Financial Interests, Personal, Advisory Role: Eisai, Roche, AstraZeneca, Xenthera Inc.; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, MSD, Ipsen; Financial Interests, Personal, Other, Honoraria: Eisai, Incyte, Roche, AstraZeneca. D. Palmer: Financial Interests, Institutional, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: MSD, AstraZeneca, Eisai, Sirtex Medical, Roche, Boston Scientific, Viatris; Financial Interests, Personal, Research Grant: Bristol Myers Squibb, Bayer, Sirtex Medical, AstraZeneca, Nucana. A. Baron: Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, Lilly. J. Park: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, AstraZeneca, Roche/Genentech, BeiGene; Financial Interests, Personal, Speaker’s Bureau: Bayer, Eisai, AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche/Genentech; Financial Interests, Institutional, Other: Genexine, onconic therapeutics, Eutilex; Financial Interests, Personal, Other, Honoraria: Bayer, Eisai, Ipsen, Roche/Genentech; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb Japan, Ono Pharmaceutical, AstraZeneca, Roche/Genentech, MSD, Exelixis, Eisai. K. Estenson, V. Christou, M. Ren: Financial Interests, Personal, Full or part-time Employment: Eisai. A. Vogel: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Böhringer Mannheim, Eisai, Incyte, Ipsen, Janssen, MSD, Pierre Fabre, Roche, Servier, Tyra, Tahio; Financial Interests, Personal, Invited Speaker: BMS, Eisai, Ipsen, Lilly, MSD, Roche, AstraZeneca, Roche, MSD, BeiGene, Jiangsu Hengrui Medicines. All other authors have declared no conflicts of interest.