Abstract 835P
Background
The use of targeted therapies (TT) and checkpoint inhibitors (IT) in patients with melanoma significantly prolonged survival, especially in the group of patients with BRAF-mutated melanoma. The aim of this study was to evaluate real-life outcomes of advanced melanoma second line therapy in TT-IT and IT-TT sequence with BRAFi/MEKi combination or anti-PD1 agent.
Methods
Consecutive patients with BRAF mutation-positive unresectable or metastatic melanoma treated sequentially with TT-IT (BRAF and MEK inhibitors then anti-PD-1 antibody) and IT-TT were included in the study, patients treated with IT or TT in the first line only without switch to another therapy were not included. All the basic factors and response to treatment were analyzed in 1st and 2nd lines. Data cut-off was 31/Jan/2022.
Results
In total 304 patients were enrolled. 207 (68%) patients were treated with TT-IT and 97 (32%) with IT-TT. The median age was 58 years. At the time of treatment initiation, there were no differences between the TT-IT and IT-TT groups in age, sex, primary lesion location, TMN stage, and presence of brain metastases. In the TT-IT group, there were significantly more patients in ECOG 2 and with elevated LDH. However, after 1st line TT no such differences were found at 2nd line treatment initiation. There were also no statistically significant difference in median PFS between 1st line TT (TT 1L) and 2nd line TT (TT 2L) - p = 0.1628; as well as for the 1st and 2nd line IT (IT 1L vs IT 2L) - p = 0.2484. More objective responses were achieved in the TT 1L and TT 2L groups than in the IT 1L and IT 2L groups, 56% and 57% vs. 15% and 20%, respectively. In the IT groups IT 1L and IT 2L PD was recorded in 59% and 61% at the time of analysis, respectively. There was no correlation between OR in 1st and 2nd line of treatment. 21 % of patient in TT-IT and 22% in IT-TT were enrolled in 3rd line.
Conclusions
There is no difference in PFS and treatment response for TT and IT depending on the 1st or 2nd line for BRAFi/MEKi and anti-PD1 therapies. BRAF-mutated patients treated with TT progressing on first line TT therapy are still candidates for IT, even in those patients with initially elevated LDH at 1st line therapy. New factors responsible for resistance to IT should be investigated.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
B. Cybulska-Stopa: Financial Interests, Personal, Invited Speaker: BMS, Novartis, Roche, Pierre Fabre, MSD; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Sponsor/Funding: Novartis, Roche, Pierre Fabre, MSD. A.M. Czarnecka: Financial Interests, Personal, Invited Speaker: BMS, MSD, Novartis, Pierre Fabre. M. Ziętek: Other, Personal, Invited Speaker: BMS, Novartis, Roche, Pierre Fabre, MSD. R. Dziura: Financial Interests, Personal, Invited Speaker: BMS, Novartis, Roche, Pierre Fabre, MSD. L. Galus: Financial Interests, Personal, Invited Speaker: BMS, Novartis, Roche, Pierre Fabre, MSD. J. Seredynska: Financial Interests, Personal, Invited Speaker: BMS, Novartis, Roche, Pierre Fabre, MSD. A. Kamycka: Financial Interests, Personal, Invited Speaker: BMS, Novartis, Roche, Pierre Fabre, MSD. W. Bal: Financial Interests, Personal, Invited Speaker: BMS, Novartis, Roche, Pierre Fabre, MSD. T. Kubiatowski: Financial Interests, Personal, Invited Speaker: BMS, Novartis, Roche, Pierre Fabre, MSD. T. Switaj: Financial Interests, Personal, Invited Speaker: BMS, Novartis, Roche, Pierre Fabre, MSD. N. Kempa-Kaminska: Financial Interests, Personal, Invited Speaker: BMS, Roche. P. Rogala: Financial Interests, Personal, Invited Speaker: BMS, Novartis, Roche, Pierre Fabre, MSD. G. Kamińska-Winciorek: Financial Interests, Personal, Invited Speaker: BMS, Novartis, Roche, Pierre Fabre, MSD; Financial Interests, Personal, Advisory Role: MSD. R. Suwinski: Financial Interests, Personal, Invited Speaker: BMS, Astellas, Novartis, Roche, Pierre Fabre, MSD. J. Mackiewicz: Financial Interests, Personal, Invited Speaker: BMS, Novartis, Roche, Pierre Fabre, MSD; Financial Interests, Personal, Funding: BMS, MSD; Financial Interests, Personal, Advisory Role: BMs, MSD. P. Rutkowski: Financial Interests, Personal, Invited Speaker, honoraria for lectures: MSD, BMS, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre, Merck, Sanofi, Blueprint Medicines, Philogen; Financial Interests, Personal, Invited Speaker: Merck, Sanofi, Novartis; Financial Interests, Institutional, Research Grant, research grant for ISS: Pfzer; Financial Interests, Institutional, Funding, research grant for institution: BMS; Non-Financial Interests, Invited Speaker: Polish Society of Surgical Oncology; Non-Financial Interests, Officer: ASCO; Non-Financial Interests, Invited Speaker, President Elect: Polish Oncological Society. All other authors have declared no conflicts of interest.