Abstract 5352
Background
BM are common in pts with metastatic melanoma and are usually associated with a pejorative prognosis. Thus, understanding incidence, response, progression, and outcomes of pts with BM treated with immunotherapy is of substantial clinical relevance. This retrospective analysis was conducted to evaluate the efficacy and safety of pembro in pts with and without BM at baseline in KEYNOTE-001, -002, and -006.
Methods
Pts with advanced melanoma who had previously treated and stable BM for ≥4 weeks prior to enrollment in KEYNOTE-001, -002, and -006 received pembro: 2 mg/kg Q3W, 10 mg/kg Q2W, or 10 mg/kg Q3W. Groups were pooled given similar efficacy. End points included OS, PFS, ORR, DOR, and safety.
Results
Of the 1561 pts treated with pembro, 157 (10%) had BM at baseline. Median follow-up was 19.2 mo (range 0.2-43.0) in pts with BM vs 19.4 mo (range 0.2-47.7) in pts without BM. Baseline characteristics were similar between cohorts. 24-month OS and PFS, ORR, DCR, and DOR were equivalent (Table). PD occurred in 40% and 42%, respectively. PD occurred in the brain in 59% of pts with BM compared with 10% of pts without BM. AEs of any grade were reported in 97% of pts with BM and 98% of pts without BM; TRAEs were reported in 76% of pts with BM and 81% of pts without BM; grade 3-5 TRAEs were reported in 14% and 17%, respectively. 9% and 8% discontinued due to a TRAE. 2 pts without BM died due to a TRAE.Table: 1248PD
Efficacy of pembro in pts with or without BM at baseline
| Patients With BM N = 157 | Patients Without BM N = 1404 | |
|---|---|---|
| 24-mo OS (95% CI), % | 45 (34.9-54.1) | 49.0 (45.4-52.3) |
| 24-mo PFS (95% CI), % | 26 (18.7-33.2) | 26 (24.1-28.9) |
| ORRa, % | 33 | 32 |
| DCRa,b, % | 48 | 48 |
| CR, % | 8 | 10 |
| PR, % | 25 | 22 |
| SD, % | 13 | 14 |
| PD, % | 39 | 42 |
| DOR (range), mo | NR (1.3+ to 31.3+) | NR (1.1+ to 38.8+) |
Extracranial responses. bIncludes non-CR/non-PD pts.
Conclusions
In this pooled retrospective analysis of KEYNOTE-001, -002, and -006, overall efficacy and safety were similar in pts who received pembro regardless of baseline stable BM after local therapy. In pts who had PD, PD occurred in the brain more often in pts with BM at baseline versus those without. These data suggest that pembro is a safe, efficacious treatment for advanced melanoma in pts with and without previously-treated and stable BM at baseline.
Clinical trial identification
NCT01295827 (first posted Feb 15, 2011); NCT01704287 (first posted Oct 11, 2012); NCT01866319 (first posted May 31, 2013).
Legal entity responsible for the study
Merck & Co., Inc.
Funding
Merck & Co., Inc.
Editorial Acknowledgement
Medical writing and/or editorial assistance was provided by Trisha Stankiewicz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
O. Hamid: Advisory board member: Amgen, Novartis, Roche, BMS, Merck; Speaker's bureau: BMS, Genentech, Novartis, Amgen; Honoraria, Travel expenses: Amgen, Novartis, Roche, BMS, Merck; Other: Contracted research institution: AstraZeneca, BMS, Celldex, Genentech, Immunocore, Incyte, Merck, Merck Serono, MedImmune, Novartis, Pfizer, Rinat, Roche. A. Ribas: Stock ownership: Lutris, PACT, Tango; Advisory board member: Advaxis, Arcus, BioncoTech, Compugen, CytomX, Five Prime, FLX-Bio, ImaginAb, Isoplexis, Kite-Gilead, Rgenix; Honoraria for Amgen, BMS, Chugai, Genentech, Merck, Novartis, Roche. A. Daud: Stock ownership: Oncosec, Cingularity; Advisory board member: Merck, BMS, Gentech/Roche, Regeneron; Research funding: Merck, BMS, Gentech/Roche, Regeneron, Incyte, Curis. M.O. Butler: Advisory board member: Merck Canada, BMS, EMD Serono, Immunovaccine, Immunocore, Novartis. M.S. Carlino: Honoraria: MSD, BMS, Novartis; Consultant/advisory: MSD, BMS, Novartis, Amgen. W-J. Hwu: Consulting/Advisory for Merck, Array; Research funding: Merck, BMS, MedImmune, GSK. G.V. Long: Honoraria: BMS, MSD, Roche, Novartis, Incyte; Consultant/advisory: BMS, Roche, Amgen, MSD, Novartis, Array, Pierre Fabre, Incycte; Travel, accomodations and expenses: MSD, Roche (travel support to conference). F.S. Hodi: Advisory board member: Merck, Bristol-Myers Squibb, Novartis, EMD Serono, Sanofi; Research funding (institution): Bristol-Myers Squibb. N.I. Khushalani: Stock ownership: Mazor Robotics, Bellicum Pharmaceuticals; Advisory board member: Bristol Myers-Squibb, EMD Serono, HUYA Bioscience, Regeneron, Genentech; Research funding: Bristol Myers-Squibb, Merck, Novartis, GlaxoSmithKline, HUYA, Regeneron, Amgen (all to Institution); Other: Data safety monitoring board: AstraZeneca. C.U. Blank: Stock: Verastem; Consulting/advisory: MSD, BMS, Roche, Novartis, Pfizer, Lilly, GSK; Research funding: Novartis, BMS; Travel, accommodations: MSD, Pfizer, Roche. C. Loquai: Advisory board member: BMS, Novartis, Roche, MSD, Amgen, Pierre Fabre, Leo; Speakers’ bureau: BMS, Novartis, Roche, MSD, Amgen, Pierre Fabre, Leo; Honoraria: BMS, Novartis, Roche, MSD, Amgen, Pierre Fabre, Leo; Travel expenses, including accommodations: BMS, Novartis, Roche, MSD, Amgen, Pierre Fabre, Leo. J. Lin, S.J. Diede: Employee, Stockholder: Merck. C. Robert: Honoraria, Consultant/advisory: BMS, Merck, GSK, Roche, Amgen, Novartis. All other authors have declared no conflicts of interest.