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Clinical outcomes and management following progressive disease with anti-PD-(L)1 therapy in patients with advanced
Jeremy Mo1, Anne Zaremba2, Andrisha-Jade Inderjeeth3
1Westmead Hospital, Westmead, Australia.
Aim:
Merkel Cell Carcinoma (MCC) is a rare skin cancer with a rising incidence worldwide. Anti-programmed death-1/ligand-1 (anti-PD-(L)1) therapies are effective for the treatment of advanced MCC. This study examines patterns of response / progression of advanced MCC to anti-PD-(L)1 therapies and describes subsequent management.
Method:
This is a multi-centre international retrospective cohort study with data collected up to May 2023 from 17 centres across 6 countries. Outcomes included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) for anti-PD-(L)1 and subsequent therapy.
Results:
One-hundred and eighty-five advanced MCC patients received anti-PD-(L)1 therapy. At median follow-up of 28.7 months (95 % CI: 21.4-38.3), ORR was 57.3 %, median DOR was 42.8 months (95 % CI, 25.8 - not reached (NR)), median PFS was 14 months (95 % CI, 8.1- 19.8), and median OS was 42.8 months (95 % CI, 30.3 - NR). One-hundred and eight patients (59 %) experienced progressive disease; 50 % (n = 54/108) with primary resistance and 26 % (n = 28/108) with secondary resistance. Fifty patients (27 %; n = 50/185) received subsequent systemic therapies (+/- local therapy) with response data; 18 (36 %; n = 18/50) received doublet platinum chemotherapy (ORR 67 %, DOR 5.0 months [95 % CI; 3.7 - NR]) and 16 (32 %; n = 16/50) were rechallenged with anti-PD-(L)1 (ORR 56 %, DOR 20.2 months [95 % CI; 8.3 - NR]).
Conclusion:
The most common subsequent treatment for patients with primary resistance was chemotherapy, while those with secondary resistance most frequently underwent further anti-PD-(L)1 therapy in combination with other therapies. Despite both therapies demonstrating promising ORR, doublet platinum chemotherapy had a poorer DOR compared to anti-PD-(L)1 rechallenge.
Insights
Advanced Merkel Cell Carcinoma (MCC) patients show significant response to anti-programmed death-1/ligand-1 (anti-PD-(L)1) therapies. Subsequent treatments vary based on resistance type, with chemotherapy for primary resistance and anti-PD-(L)1 rechallenge for secondary resistance.
Area of Science:
- Oncology
- Immunotherapy
- Dermatology
Background:
- Merkel Cell Carcinoma (MCC) is a rare skin cancer with increasing incidence.
- Anti-programmed death-1/ligand-1 (anti-PD-(L)1) therapies are established treatments for advanced MCC.
Purpose of the Study:
- To analyze response and progression patterns in advanced MCC patients treated with anti-PD-(L)1.
- To describe subsequent management strategies for patients with advanced MCC.
Main Methods:
- Multi-center international retrospective cohort study.
- Data collected from 17 centers across 6 countries up to May 2023.
- Evaluated objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).
Main Results:
- 185 advanced MCC patients received anti-PD-(L)1 therapy with a 57.3% ORR and 14-month median PFS.
- 59% of patients experienced disease progression; 50% had primary resistance and 26% had secondary resistance.
- Subsequent therapies included chemotherapy (ORR 67%) and anti-PD-(L)1 rechallenge (ORR 56%).
Conclusions:
- Chemotherapy was the primary subsequent treatment for primary resistance.
- Anti-PD-(L)1 rechallenge was common for secondary resistance.
- Doublet platinum chemotherapy showed a shorter DOR than anti-PD-(L)1 rechallenge.
