Patterns of response/progression and management following progressive disease (PD) with anti-PD-(L)1 (PD(L)1) in patients (pts) with advanced Merkel cell carcinoma (MCC)

Abstract

BACKGROUND: PD(L)1 has become 1st line therapy for advanced MCC, however resistance occurs in approximately half of pts. We aim to: (1) evaluate patterns and predictors of response/PD to PD(L)1; (2) study the management following PD to PDL1. METHODS: Advanced MCC pts treated with PD(L)1 at 13 international centres were included. Demographics, baseline characteristics, outcomes and subsequent treatments were examined. Multivariable analyses (MVA) identified factors associated with response. RESULTS: 171 MCC pts were included; 111 (65%) were male, median (med) age 75 years (range 38-92). 52 pts (30%) had a history of a malignancy other than complex skin cancer and 23 (13%) were immunosuppressed. 86 (50%) pts had visceral disease; 37 (22%) with bone, 30 (18%) with liver and 17 (10%) with lung metastases (mets). With a med follow-up of 31 months (mo; 95% CI, 21 - 40), the response rate (RR) was 60% (37% complete response [CR]) and 30% (n=52) had PD. In a MVA including demographics, sites of mets and full blood count, only higher haemoglobin and eosinophils were associated with response. Site-specific CR/partial response (PR) was most common in bone (68%) and liver mets (63%); while site-specific PD was most common in lymph nodes (LN; 27%) and subcutaneous (subcut; 24%) mets. 24-mo PFS and OS were 39% (95% CI, 32 - 49) and 61% (95% CI, 53 - 70), respectively. From 98 (57%) progressing pts; 56 (57%) had upfront PD or <6 mo of stable disease (SD) prior to PD (innate resistance = IR) and 42 (43%) had PD following CR/PR or SD>6 mo (acquired resistance = AR). 70 (71%) had subsequent treatment with 59 (61%) having systemic +/- local therapy (Table). [Formula presented] CONCLUSIONS: Patterns of response/PD to PD(L)1 in MCC differ from other skin cancers with greater response in liver/bone versus LN/subcut, suggesting unique MCC biology. Most IR pts received chemotherapy as subsequent therapy while AR pts were re-challenged with PD(L)1, and both demonstrated promising RR.