Abstract 800P
Background
NNT and NNH are simple, easy-to-read devices that allow to estimate magnitude of benefit and harm of a therapeutic intervention. This study aims to apply these numbers to describe efficacy and safety of pembrolizumab (Pembro) and dabrafenib plus trametinib (D-T) as Adj therapies in St II-III resected melanoma.
Methods
Three phase III trials evaluating Adj therapies in melanoma versus placebo (KEYNOTE-716 [KN-716], KEYNOTE-054 [KN-054] and COMBI-AD [C-AD]) were considered for data extraction. NNT for relapse-free survival (RFS) was calculated as the inverse of the absolute risk reduction, rounded up to the nearest whole number. NNH for grade ≥ 3 (AEG≥3) and grade 5 adverse events (AEG5) was also calculated as the inverse of the absolute risk increase, rounded down to the nearest whole number. Calculations were performed in the overall population and in principal subgroups (SG), if feasible.
Results
NNTs and NNHs are listed in the table. In KN-716, lower NNT values were obtained in the T3b and T4a SG, as compared to overall population and T4b; oppositely, NNT tended to a slight decrease as the St worsened in both KN-054 and C-AD. NNTs were also a bit lower in the SG with macroscopic lymph node invasion (LNi) in KN-054 only and with both ulceration (ulc) and macroscopic LNi in KN-054 and C-AD. NNHs for AEG≥3 were 3 for C-AD, 7 for KN-054 and 11 KN-716, while NNHs for AEG5 were very high across all trials. Table: 800P
NNT and NNH for melanoma Adj therapies
| C-AD | KN-054 | KN-716 | |
| Experimental treatment | D-T | Pembro | Pembro |
| Population | St III BRAF-mutated | St III | St II |
| Overall | - | 7 | 12 |
| BRAF wild type | - | 7 | - |
| BRAF mutated | 6 | 6 | - |
| St IIIA | 7 | 91 | - |
| St IIIB | 5 | 7 | - |
| St IIIC | 5 | 6 | - |
| St II - T3b | - | - | 8 |
| St II - T4a | - | - | 101 |
| St II - T4b | - | - | 271 |
| Microscopic LNi | 5 | 9 | - |
| Macroscopic LNi | 5 | 6 | - |
| No ulc/Microscopic LNi | 7 | 91 | - |
| Ulc/Macroscopic LNi | 4 | 5 | - |
| AEG≥3 | 3 | 7 | 11 |
| AEG5 | 435 | 5092 | -162 |
1 no RFS benefit demonstrated at SG analysis 2 treatment-related AEG5.
Conclusions
Analyzing NNT and NNH offered us a simple, quick and useful overview on efficacy and safety of Pembro and D-T in this setting. If validated, these data may support their use in clinical decision-making process. Despite study limitations, we suggest that some clinical SG could have a little more favorable risk-to-benefit ratio.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M. Garutti: Financial Interests, Personal, Advisory Board: Novartis, Eli Lilly, Pierre-Fabre. M. Bartoletti: Financial Interests, Personal, Advisory Board: DSK. F. Puglisi: Financial Interests, Personal, Research Grant: AstraZeneca, Eisai; Financial Interests, Personal and Institutional, Research Grant: Roche; Financial Interests, Personal, Other, personal fees and other: Roche, Eli Lilly; Financial Interests, Personal, Other, personal fees: Amgen, Ipsen, MSD, Takeda; Financial Interests, Personal, Other: Eisai, Novartis, Pfizer. All other authors have declared no conflicts of interest.