The role of local therapy in the treatment of solitary melanoma progression on immune checkpoint inhibition: A multicentre retrospective analysis

Abstract

Introduction: In patients with metastatic melanoma, progression of a single tumour lesion (solitary progression) after response to immune checkpoint inhibition (ICI) is increasingly treated with local therapy. We evaluated the role of local therapy for solitary progression in melanoma. Patients and methods: Patients with metastatic melanoma treated with ICI between 2010 and 2019 with solitary progression as first progressive event were included from 17 centres in 9 countries. Follow-up and survival are reported from ICI initiation. Results: We identified 294 patients with solitary progression after stable disease in 15%, partial response in 55% and complete response in 30%. The median follow-up was 43 months; the median time to solitary progression was 13 months, and the median time to subsequent progression after treatment of solitary progression (TTSP) was 33 months. The estimated 3-year overall survival (OS) was 79%; median OS was not reached. Treatment consisted of systemic therapy (18%), local therapy (36%), both combined (42%) or active surveillance (4%). In 44% of patients treated for solitary progression, no subsequent progression occurred. For solitary progression during ICI (n Z 143), the median TTSP was 29 months. Both TTSP and OS were similar for local therapy, ICI continuation and both combined. For solitary progression post ICI (n Z 151), the median TTSP was 35 months. TTSP was higher for ICI recommencement plus local therapy than local therapy or ICI recommencement alone (p Z 0.006), without OS differences. Conclusion: Almost half of patients with melanoma treated for solitary progression after initial response to ICI had no subsequent progression. This study suggests that local therapy can benefit patients and is associated with favourable long-term outcomes.

The Role of Stereotactic Radiotherapy in the Management of Melanoma, A Retrospective Single Institute Preliminary Study of 30 Patients

“…Due to this specific attribute, oligoprogressive disease can be treated efficiently with various local therapies, and thereby acquired resistance can be controlled, and we are allowed to continue the previously started, effective systemic therapy. Brain metastases are common in melanoma compared to other malignancies, which may explain why 22 (74%) of our patients were treated for cerebral metastases, but the tumor can often metastasize other peripheral regions ( 6 , 15 , 16 ). The result of several retrospective analyses concluded that some patients treated with checkpoint inhibitors who developed progression had benefited from continuing the treatment.…”

Efficacy of stereotactic ablative radiotherapy (SABR) during anti-PD-1 in oligoprogressive non-small cell lung cancer and melanoma—a prospective multicenter observational study pointing out new unmet needs

“…First, this seems to be the only prospective study to evaluate the efficacy of SABR after progression to anti-PD-1 in patients with metastatic NSCLC and melanoma. So far, only retrospective series evaluated this (7,9,12). The only prospective trials treated patients with SABR at the start of ICI, to potentially increase response rates by boosting the anti-tumor immunity by radiotherapy (6,13,14).…”

“…To overcome these resistance mechanisms and increase response rates, combination therapies with ICI are investigated. A growing number of reports show that the combination of stereotactic ablative radiotherapy (SABR) and ICI is safe and could increase progression-free survival (PFS) and overall survival (OS) (5)(6)(7)(8)(9). There are even reports of spontaneous regression of non-target lesions, also known as the abscopal effect, possibly due to a synergistic effect between SABR and ICI leading to immunogenic cell death (5,10).…”

Radiomic analysis of patient and inter-organ heterogeneity in response to immunotherapies and BRAF targeted therapy in metastatic melanoma

“…Particularly myeloid cells are known to have a complex phenotypic distribution across organs 12 and impact on antitumor immunity 13 14 . Local therapies for oligometastatic progression to extend BRAF or immunotherapy benefit is a clinical strategy in melanoma oncology 15 16 . An unmet need remains for non-invasive biomarkers of lesion and organ-specific response to inform treatment selection and the study of tumor resistance.…”