Abstract 1077P
Background
Immunotherapy (IO) and targeted therapy (TT) have revolutionized the treatment of pts with MBM, but clinical data on their efficacy are scarce. This analysis summarizes available RWE on the systemic treatment outcomes for pts with MBM.
Methods
An SLR of RWE for any systemic treatment in pts with MBM was conducted by searching Embase® and MEDLINE® databases from inception to February 23, 2020, and ASCO, AACR, ESMO, SMR, and EANO proceedings for 2018–2020. Records were screened by 2 investigators according to PICOS criteria. Records that reported OS outcomes on individual IO or TT therapies (with/without stereotactic radiosurgery [SRS]) were included in the MA. Kaplan–Meier (KM) curves for overall survival (OS) were digitized and converted to pseudo-individual pt data using the Guyot algorithm. MAs were performed by pooling KM curves and naive pooling of weighted median OS (mOS). For single-intervention studies, only reported values were used.
Results
A total of 57 publications (pertaining to 56 studies) were included for evidence synthesis. A total of 21 KM curves on 6 interventions and 1371 pts were digitized. mOS from pooled KM curves was numerically longer for nivolumab plus ipilimumab (NIVO + IPI; 20.6 mo; 95% CI, 17.0–22.9) versus other interventions (mOS ranging from 7.1–13.9 mo; table). Similar results were noted with the naive pooling method. Reporting on prior therapies, pt characteristics, and neurological symptoms was inconsistent.
Conclusions
RWE for MBM is scarce and heterogeneous; further research is warranted on optimal treatment for these pts. This SLR and MA suggest a clinical advantage with NIVO + IPI versus other systemic agents in pts with MBM. However, data interpretation is limited by evidence heterogeneity, inconsistent reporting, and small sample sizes. More consistent reporting of pt characteristics and outcomes is needed. Table: 1077P
MA results
| Treatment | Pooled KM curves | Weighted estimatesa | ||||
| No. of KM curves | Pooled sample size, n | Median OS, mo (95% CI) | No. of cohorts | Pooled sample size, n | Median OS, mo | |
| DAB | – | – | – | 1 | 17 | 5.6b |
| DAB/DAB + TMB | 1 | 132 | 9.5a (6.7–12.4) | 1 | 132 | 9.5b |
| VMB | 5 | 395 | 13.0 (10.9–13.9) | 8 | 439 | 7.0 |
| VMB + SRS | – | – | – | 1 | 24 | 11.9b |
| IPI | 5 | 105 | 7.1 (5.7–9.3) | 5 | 134 | 6.4 |
| IPI + SRS | 7 | 143 | 13.9 (10.7–16.5) | 3 | 72 | 15.2 |
| IPI + SRS (after IPI) | – | – | – | 1 | 14 | 6.4b |
| IPI + SRS (before/during IPI) | – | – | – | 1 | 32 | 13.8b |
| NIVO + IPI | 2 | 543 | 20.6 (17.0–22.9) | 1 | 380 | 19.0b |
| NIVO | 1 | 53 | 12.4a (6.2–NR) | 1 | 53 | 12.4b |
aWeighted by sample size. bAs reported in original publication. CI, confidence interval; DAB, dabrafenib; IPI, ipilimumab; NIVO, nivolumab; NR not reached; TMB, trametinib; VMB, vemurafenib.
Clinical trial identification
Editorial acknowledgement
Editorial assistance was provided by Mark Palangio and Michele Salernitano of Ashfield MedComms, an Ashfield Health company, funded by Bristol Myers Squibb.
Legal entity responsible for the study
Bristol Myers Squibb.
Funding
Bristol Myers Squibb.
Disclosure
G.V. Long: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Merck MSD; Financial Interests, Personal, Advisory Role: Specialized Therapeutics; Financial Interests, Personal, Advisory Role: Pierre-Fabre; Financial Interests, Personal, Advisory Role: QBiotics; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim. H.A. Tawbi: Financial Interests, Personal and Institutional, Other, Consulting fees; research funding to institution: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Other, Consulting fees; research funding to institution: Merck; Financial Interests, Personal and Institutional, Other, Consulting fees; research funding to institution: Novartis; Financial Interests, Personal and Institutional, Other, Consulting fees; research funding to institution: Genentech; Financial Interests, Personal, Other, Consulting fees: Eisai; Financial Interests, Personal, Other, Consulting fees: Iovance; Financial Interests, Institutional, Funding: GlaxoSmithKline; Financial Interests, Institutional, Funding: Celgene. N. Meyer: Financial Interests, Personal and Institutional, Other: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Other: MSD; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other: Pierre Fabre; Financial Interests, Personal, Other: Sanofi; Financial Interests, Personal, Other: Sun Pharma. B. Breznen: Financial Interests, Personal, Other, Contract fees: Evidinno Inc.. C. Vyas: Financial Interests, Personal, Other, Employee; stock ownership: Bristol Myers Squibb. L. Leung: Financial Interests, Personal, Other: Bristol Myers Squibb. A. Moshyk: Financial Interests, Personal, Other, Employee; shareholder: Bristol Myers Squibb. D. Pushkarna: Financial Interests, Personal, Other: Bristol Myers Squibb. P. Thakkar: Financial Interests, Personal, Other, Employee; stock and share ownership: Bristol Myers Squibb. M.S. Fazeli: Financial Interests, Personal, Other: Bristol Myers Squibb. S. Kotapati: Financial Interests, Personal, Full or part-time Employment, Employee stock ownership and benefits: Bristol Myers Squibb. D. Schadendorf: Financial Interests, Personal, Other, Patient fees to institution; Consulting or advisory role; honoraria; travel, accommodations, expenses: Roche/Genentech; Financial Interests, Personal and Institutional, Other, Patient fees and research grant to institution; Consulting or advisory role; honoraria; speakers bureau; travel, accommodations, expenses; research funding: Novartis; Financial Interests, Personal and Institutional, Other, Patient fees and research grant to institution; Consulting or advisory role; honoraria; speakers bureau; travel, accommodations, expenses; research funding: Bristol Myers Squibb; Financial Interests, Personal, Other, Patient fees to institution; Consulting or advisory role; honoraria; travel, accommodations, expenses: Merck Serono; Financial Interests, Personal, Other, Patient fees to institution; Consulting or advisory role; honoraria; speakers bureau; travel, accommodations, expenses: Amgen; Financial Interests, Personal, Other, Consulting or advisory role; honoraria: Immunocore; Financial Interests, Personal, Other, Consulting or advisory role; speakers bureau; honoraria: Incyte; Financial Interests, Personal, Other, Patient fees to institution; Consulting or advisory role; honoraria: 4SC; Financial Interests, Personal, Other, Patient fees to institution; Consulting or advisory role; speakers bureau; honoraria: Pierre Fabre; Financial Interests, Personal, Other, Consulting or advisory role: Mologen; Financial Interests, Personal, Other, Patient fees to institution; Consulting or advisory role: Sanofi/Regeneron; Financial Interests, Personal, Other, Honoraria: Array BioPharma; Financial Interests, Personal, Other, Honoraria: InFlaRx; Financial Interests, Personal, Other, Patient fees to institution; Honoraria: Philogen; Financial Interests, Personal, Other, Patient fees to institution; Honoraria: Regeneron; Financial Interests, Personal, Other, Patient fees to institution; Consulting or advisory role; honoraria; travel, accommodations, expenses: Merck/MSD; Financial Interests, Personal, Other, Honoraria: Sandoz/Hexal; Financial Interests, Personal, Other, Honoraria: Neracare.