Abstract 824P
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). Table: 824P
| Subsequent Systemic Therapy | N(%) | IR | AR | ||
| N(%) | RR | N(%) | RR | ||
| Carboplatin/Etoposide | 20 (34) | 13(65) | 31% | 7(35) | 71% |
| PD(L)1 | 17 (29) | 5 (29) | 40% | 12 (71) | 50% |
| Ipilimumab + PD(L)1 | 5 (8) | 4 (80) | 50% | 1 (20) | 0% |
| Others | 17 (29) |
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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Zaremba: Financial Interests, Personal, Other, Travel Support: Novartis, Sanofi Grenzyme, Pierre Fabre, Bristol Myers Squibb. C. Gaudy Marqueste: Financial Interests, Personal, Advisory Board, Travel expenses: BMS, MSD; Non-Financial Interests, Personal, Principal Investigator: Sanofi, Regeneron, Incyte, Pierre Fabre, Kartos, Replimune, InflaRx. A. Bohne: Financial Interests, Personal, Other, Travel Support: Sun Pharma, Pierre-Fabre, Bristol Myers Squibb. A. Guminski: Financial Interests, Personal, Advisory Board: Regeneron, MSD, Pfizer; Financial Interests, Personal, Invited Speaker, Educational meeting: BMS; Non-Financial Interests, Institutional, Research Grant: AstraZeneca. O.A. Michielin: Financial Interests, Institutional, Invited Speaker: BMS, Amgen, Pierre Fabre, Roche, BMS; Financial Interests, Institutional, Advisory Board: BMS, Amgen, Roche, Novartis, Pierre Fabre, MSD; Financial Interests, Personal, Other, Advisory Role: BMS, MSD, Roche, Novartis, Pierre Fabre, Amgen, GSL; Financial Interests, Institutional, Research Grant: BMS, MSD, Pierre Fabre, Amgen, Merck; Financial Interests, Institutional, Funding: BMS, MSD, Pierre Fabre, Amgen, MSD; Non-Financial Interests, Principal Investigator: BMS, MSD, Amgen, Roche, Pierre Fabre, Novartis. W. Xu: Financial Interests, Personal, Advisory Board, Speaker and Research funding: Merck Serono; Financial Interests, Personal, Advisory Board, Speaker: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: AZD. C. Lebbe: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, MSD, Novartis, Amgen, Roche, Merck Serono, Sanofi, Pierre Fabre; Financial Interests, Personal, Funding: Roche, Bristol Myers Squibb; Non-Financial Interests, Advisory Role: Bristol Myers Squibb, MSD, Novartis, Amgen, Roche, Merck Serono, Sanofi, Pierre Fabre; Other, Honoraria, Speaker's Bureau: Roche; Other, Honoraira, Speaker's bureau, Travel, Accommodations, Expenses: Bristol Myers Squibb; Other, Honoraria, Speaker's bureau, Travel, Accommodations, Expenses: Novartis, MSD; Other, Honoraria, Speaker's bureau: Amgen; Other, Honoraria, Travel, Accommodations, Expenses: Pierre Fabre; Other, Honoraria,: Pfizer; Other, Honoraria: Incyte; Other,Travel, accommodations, Expenses: Sanofi. S.K. Sandhu: Financial Interests, Institutional, Advisory Board, I have served on advisory boards for BMS. The contracts for my role are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: Bristol Myer Squib; Financial Interests, Institutional, Advisory Board, I have served on advisory boards for MSD. The e contracts for my role are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: Merck Sharp and Dohme; Financial Interests, Institutional, Advisory Board, I have served on advisory boards for AstraZeneca. The contracts for my role as an advisor are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: AstraZeneca; Financial Interests, Institutional, Advisory Board, I have served on advisory boards for Novartis. The contracts for my role as an advisor are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: Novartis; Financial Interests, Institutional, Advisory Board, I have served on an advisory board for Merck Serono. The contracts for my service are set up with the institution and funds go into a research fund at the Peter MacCallum Cancer Centre: Merck Serono; Financial Interests, Institutional, Research Grant, My institution receives grant funding to run an investigator initiated trial that I lead: Novartis, Genentech, Amgen, AstraZeneca, Merck Serono, Merck Sharp and Dohme; Non-Financial Interests, Principal Investigator, I am a principal investigator on several of Janssen sponsored studies and don't receive any renumeration for this: Janssen; Non-Financial Interests, Principal Investigator, I am a principal investigator on several Novartis sponsored studies and don’t receive any renumeration for this: Novartis; Non-Financial Interests, Principal Investigator, I am a principal investigator on several of Genentech sponsored studies and don't receive any renumeration for this: Genentech; Non-Financial Interests, Principal Investigator, I am a principal investigator on several of Bristol Myers Squibb sponsored studies and don't receive any renumeration for this: Bristol Myers Squibb; Non-Financial Interests, Other, I serve on the Independent Safety and Data Monitoring committee for 2 of Novartis sponsored studies and don’t receive any compensation for this: Novartis; Non-Financial Interests, Principal Investigator, I am the Principal Investigator for several AstraZeneca sponsored studies and am not remunerated for this: AstraZeneca; Non-Financial Interests, Other, I serve on the steering committee for several Janssen sponsored trials and I do not receive compensation for this: Janssen; Non-Financial Interests, Other, I serve on the steering committee for one AstraZeneca sponsored trial and I do not receive compensation for this: AstraZeneca; Non-Financial Interests, Other, I serve on the steering committee for one Genentech sponsored trials and I do not receive compensation for this: Genentech; Non-Financial Interests, Other, I serve on the steering committee for a Bristol Myers Squibb sponsored trial and I do not receive renumeration for this: Bristol Myers Squibb. L. Zimmer: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Novartis, MSD, Sunpharma, Pierre Fabre, Sanofi; Financial Interests, Personal, Other, Travel Support: Bristol Myers Squibb, MSD, Sunpharma, Pierre Fabre, Sanofi, Novartis, Amgen; Financial Interests, Personal, Invited Speaker: Novartis, MSD, Pierre Fabre, Roche; Financial Interests, Personal and Institutional, Research Grant: Novartis; Non-Financial Interests, Member: German Cancer Society, Dermatologic Cooperative Oncology Group. M.S. Carlino: Financial Interests, Personal, Advisory Role: Amgen, BMS, Eisai, Ideaya, MSD, Nektar, Novartis, Oncosec, Pierre Fabre, Qbiotics, Regeneron, Roche; Financial Interests, Personal, Funding, Honoraria: BMS, MSD, Novartis. I. Pires da Silva: Financial Interests, Personal, Invited Speaker: BMS, MSD, Roche, Novartis; Financial Interests, Personal, Funding, Travel support: BMS, MSD. All other authors have declared no conflicts of interest.