1080MO - The value of local therapy in treatment of solitary melanoma progression upon immune checkpoint inhibition

Background

Patients (pts) with stage IV melanoma can achieve long-term disease control through treatment with immune checkpoint inhibition (ICI). Disease progression in a single tumor lesion (solitary progression, SP) after initial response to ICI is often treated with local therapy. This study aimed to evaluate the benefits of local therapy for the treatment of SP during (on) or after cessation of (off) ICI.

Methods

Pts with stage IV melanoma with at least stable disease (SD) as best overall response (BOR) upon ICI and SP as first progressive event were retrospectively included from 17 centers in 9 countries.

Results

We included 294 pts with SP on anti-PD-1 (67%), anti-CTLA-4 (13%), anti-PD-1 + anti-CTLA-4 (15%) and other ICI combinations (5%). BOR prior to SP was SD (15%), partial response (55%) and complete response (30%). Local therapy was mainly surgery (56%), radiotherapy (35%) or both (5%). Median follow-up from start ICI was 43 months (m), median time to SP 13m and median time to second progression after treatment of SP (TTSP) 33m. Median overall survival (OS) was not reached, estimated 3-year OS was 79%. SP occurred in 143 pts on ICI (median 11m) and in 151 pts off ICI (median 17m from start ICI, 9m from stop ICI). SP was treated with local + systemic therapy (42%), local therapy (36%) or systemic therapy only (18%). Second progression was mostly progression at multiple sites (64% and 65% for SP on and off ICI). In pts with SP on ICI, median TTSP was 29m. Local therapy + ICI continuation (N=94) resulted in similar 3-year TTSP as local therapy (N=15) or ICI continuation only (N=14, P=0.971). OS at 3 years was superior for local therapy + ICI continuation (P=0.020). In pts with SP off ICI, median TTSP was 35m. ICI restart + local therapy (N=22, 85%) resulted in superior TTSP compared to local therapy (N=90, 41%) or ICI restart (N=18, 56%, P=0.002), without OS differences so far.

Conclusions

In pts with SP off ICI, the combination of local therapy + ICI restart was most successful in delaying further progression, but did not improve OS so far compared to single modality treatment. Local therapy + ICI continuation in pts with SP on ICI did not improve TTSP, but did improve OS. This indicates that local therapy can benefit pts.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

K.P.M. Suijkerbuijk: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pierre Fabre; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche. L. Zimmer: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pierre Fabre; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Sanofi; Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: Sunpharma. E. Kapiteijn: Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Merck; Advisory/Consultancy: Novartis; Travel/Accommodation/Expenses: Roche. C. Allayous: Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: Bristol-Myers Squibb; Travel/Accommodation/Expenses: Roche. D.B. Johnson: Advisory/Consultancy: Array Biopharma; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Incyte; Advisory/Consultancy: Merck; Advisory/Consultancy: Novartis; Travel/Accommodation/Expenses: Genentech. A. Hepner: Honoraria (institution): Novartis; Advisory/Consultancy: L.E.K. Consulting; Travel/Accommodation/Expenses: Roche. J. Mangana: Honoraria (institution), Advisory/Consultancy: Amgen; Honoraria (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Honoraria (institution), Advisory/Consultancy: Merck-Pfizer; Honoraria (institution): Novartis; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Pierre Fabre; Travel/Accommodation/Expenses: L'Oreal; Travel/Accommodation/Expenses: Ultrasun. Y. Jansen: Travel/Accommodation/Expenses: Bristol-Myers Squibb; Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Pfizer. V. Atkinson: Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Serono; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Pierre Fabre; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Travel/Accommodation/Expenses: OncoSec. E.G.E. de Vries: Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: NSABP; Advisory/Consultancy: Sanofi; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Chugai Pharma; Research grant/Funding (institution): CytomX Therapeutics; Research grant/Funding (institution): G1 Therapeutics; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Nordic Nanavector; Research grant/Funding (institution): Radius Health; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Servier; Research grant/Funding (institution): Synthon; Non-remunerated activity/ies, Chair ESMO Cancer Medicines Working Group: ESMO; Non-remunerated activity/ies, Chair RECIST committee: RECIST; Non-remunerated activity/ies, Member ESMO-MCBS working group: ESMO-MCBS. C.U. Blank: Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): NanoString; Honoraria (institution), Advisory/Consultancy: MSD; Honoraria (institution), Advisory/Consultancy: Roche; Honoraria (institution), Advisory/Consultancy: GSK; Honoraria (institution), Advisory/Consultancy: AZ; Honoraria (institution), Advisory/Consultancy: Pfizer; Honoraria (institution), Advisory/Consultancy: Lilly; Honoraria (institution), Advisory/Consultancy: GenMab; Honoraria (institution), Advisory/Consultancy: Pierre Fabre; Honoraria (self), Advisory/Consultancy: Third Rock Ventures; Shareholder/Stockholder/Stock options: Uniti Cars; Shareholder/Stockholder/Stock options: Immagene BV. M. Jalving: Honoraria (institution): Merck; Honoraria (institution): Bristol-Myers Squibb; Honoraria (institution): Novartis; Honoraria (institution): Pierre Fabre; Honoraria (institution): Tesaro; Honoraria (institution): AstraZeneca. All other authors have declared no conflicts of interest.