Abstract 1110P
Background
Anti-programmed cell death protein 1 monotherapy (PD1) leads to a favorable response in approximately 40% of advanced melanoma cases among Caucasian populations; however, two-thirds of patients (pts) show innate or acquired resistance to PD1, subsequently requiring salvage therapy. Moreover, the clinical efficacy of PD1 is lower in Asian populations. Although the potential benefits of salvage therapies after PD1 failure, including BRAF inhibitor plus MEK inhibitor (BRAFi/MEKi) and nivolumab plus ipilimumab (nivo/ipi), are being elucidated in Caucasian populations, little is known about these benefits in Asian populations. We investigated the efficacy of salvage systemic therapies in Japanese pts with melanoma after PD1 failure.
Methods
Japanese pts with advanced melanoma after PD1 failure who then proceeded to salvage systemic therapies were included from 21 Japanese institutions. The inclusion criteria were as follows: 1) ipilimumab-naive pts, 2) any line of BRAFi/MEKi, and 3) consecutive systemic therapy initiated within 2 months after PD1 failure. The primary outcome was the objective response rate (ORR), while the secondary outcomes were progression-free survival (PFS) and overall survival (OS).
Results
In total, 245 pts were included; 53.5% of the pts received ipilimumab, 15.1% received nivo/ipi, 12.2% received BRAFi/MEKi, and the remaining received cytotoxic chemotherapies as salvage therapy. BRAFi/MEKi demonstrated an ORR of 40%, significantly higher than those of ipilimumab (9.9%, P<0.001), nivo/ipi (13.5%, P=0.02), and cytotoxic chemotherapy (14.9%, P=0.02). No significant difference was observed between the ORRs of ipilimumab and nivo/ipi (P=0.55). BRAFi/MEKi also showed prolonged PFS than those of other systemic therapies (P=0.001); however, there was no significant difference between the OS of the salvage therapies (P=0.54). No significant differences were also observed between the survival of ipilimumab and nivo/ipi (PFS, P=0.29; OS, P>0.99).
Conclusions
Unlike in Caucasian populations, salvage nivo/ipi shows limited efficacy in Japanese pts, which is similar to that of ipilimumab after PD1resistance, although longer follow-up is needed in nivo/ipi arm. BRAFi/MEKi appears to be favorable compared with other regimens for BRAF-mutated melanoma.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
National Cancer Center Research and Development Fund (2020-J-3).
Disclosure
Y. Teramoto: Honoraria (self), Travel/Accommodation/Expenses: Ono pharmaceutical; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Novartis Pharma; Honoraria (self): MSD; Honoraria (self): Maruho. K. Namikawa: Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Ono Pharmaceutical; Honoraria (self): Eisai; Honoraria (self): Pharma International; Honoraria (self): Takara Bio; Honoraria (self): Tray Industries. Y. Kiniwa: Honoraria (self): Novartis,. K. Yoshino: Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Ono Pharmaceutical. S. Yoshikawa: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self): Bristol-Myers Squib; Honoraria (self): MSD; Honoraria (self): Ono Pharmaceutical. Y. Nakamura: Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Taiho Pharma; Honoraria (self): Taisho Toyama Pharma; Honoraria (self): Maruho; Honoraria (self): Kyowa Kirin. T. Funakoshi: Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical; Research grant/Funding (institution): Zenyaku Kogyo; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Minophagen Pharmaceuticals; Honoraria (self): Novartis. T. Takenouchi: Honoraria (self): Bristol-Myers; Honoraria (self): Squibb; Honoraria (self): MSD; Honoraria (self): Novartis; Honoraria (self): Ono Pharmaceutical. T. Isei: Honoraria (self): Ono Pharmaceutical; Honoraria (self): MSD; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Novartis; Honoraria (self): Takara Bio. T. Maekawa: Honoraria (self): Ono Pharmaceutical; Honoraria (self): Bristol- Myers Squibb; Honoraria (self): Novartis Pharma; Honoraria (self): MSD. Y. Fujisawa: Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self): Chugai Pharma; Honoraria (self): Eisai; Honoraria (self): Maruho; Honoraria (self): MSD; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Ono. K. Yokota: Honoraria (self): Ono Pharmaceutical; Honoraria (self): MSD; Honoraria (self): Novartis; Honoraria (self): Bristol-Myers Squibb. H. Uhara: Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb Japan; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Ono Pharmaceutical; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Kaken Pharmaceutical; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Kyowa Hakko Kirin; Honoraria (self), Research grant/Funding (institution): Maruho; Honoraria (self), Research grant/Funding (institution): Mitsubishi Tanabe Pharma; Research grant/Funding (institution): Mochida Pharmaceutical Co. Ltd.; Research grant/Funding (institution): Nihonkayaku; Honoraria (self), Research grant/Funding (institution): Pola Pharma; Research grant/Funding (institution): Taiho Pharmaceutical; Research grant/Funding (institution): Torii Pharmaceutical; Research grant/Funding (institution): Tsumura & Co.; Honoraria (self), Advisory/Consultancy: Chugai Pharma; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Janssen china R&D. S. Matsushita: Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self): MSD; Honoraria (self): Ono Pharmaceutical. S. Fukushima: Research grant/Funding (self): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (self): MSD; Honoraria (self), Research grant/Funding (self): Ono Pharmaceutical. N. Yamazaki: Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical; Research grant/Funding (institution): Takara Bio. All other authors have declared no conflicts of interest.