Efficacy of Large Use of Combined Hypofractionated Radiotherapy in a Cohort of Anti-PD-1 Monotherapy-Treated Melanoma Patients

Abstract

To assess the role of radiotherapy in anti-PD-1-treated melanoma patients, we studied retrospectively a cohort of 206 consecutive anti-PD-1 monotherapy-treated advanced melanoma patients (59% M1c/d, 50% ≥ 3 metastasis sites, 33% ECOG PS ≥ 1, 33% > 1st line, 32% elevated serum LDH) having widely (49%) received concurrent radiotherapy, with RECIST 1.1 evaluation of radiated and non-radiated lesions. Overall (OS) and progression-free (PFS) survivals were calculated using Kaplan–Meier. Radiotherapy was performed early (39 patients) or after 3 months (61 patients with confirmed anti-PD-1 failure). The first radiotherapy was hypofractionated extracranial radiotherapy to 1–2 targets (26 Gy-4 weekly sessions, 68 patients), intracranial radiosurgery (25 patients), or palliative. Globally, 67 (32.5% [95% CI: 26.1–38.9]) patients achieved complete response (CR), with 25 CR patients having been radiated. In patients failing anti-PD-1, PFS and OS from anti-PD-1 initiation were 16.8 [13.4–26.6] and 37.0 months [24.6–NA], respectively, in radiated patients, and 2.2 [1.5–2.6] and 4.3 months [2.6–7.1], respectively, in non-radiated patients (p < 0.001). Abscopal response was observed in 31.5% of evaluable patients who radiated late. No factors associated with response in radiated patients were found. No unusual adverse event was seen. High-dose radiotherapy may enhance CR rate above the 6–25% reported in anti-PD-1 monotherapy or ipilimumab + nivolumab combo studies in melanoma patients.

Increased abscopal responses after radiation therapy for oligoprogressive patients receiving immune checkpoint inhibitors?

“…Many non-randomized report-initiated ICI and SABR concurrently with uncertainties regarding additional abscopal responses. Formenti et al, Saiag et al, and Sumodhee et al observed a 18%, 31.5% and 9.5% abscopal response rates, respectively, and a 10%, 0% and 9.5% stable disease rates, respectively (4,10,11).…”

“…According to Vanpouille-Box et al the amount of cytosolic DNA which reflects the immunogenicity of tumor cells, depends on the dose per fraction ( 17 ). Interestingly, most studies that reported abscopal response used dose per fraction less than 10 Gy: 9.5 Gy for Postow et al ( 3 ), 6–9.5 Gy for Formenti et al ( 4 ), 7–8 Gy for Chicas-Sett et al ( 6 ), 6 Gy for Saiag et al ( 10 ) and Sumodhee et al ( 11 ). Of note, in these studies abscopal response was not only observed after SABR but also after conventional 3-dimensional conformal radiotherapy.…”

Global research landscape and trends of cancer radiotherapy plus immunotherapy: A bibliometric analysis

“…Preclinical studies have provided evidence that the combination of radiation with ICIs can effectively stimulate systemic antitumor immunity, highlighting the rationale for the combination of immunotherapy and RT in the clinical setting [ 1 ]. Clinical trials have further demonstrated the synergistic effectiveness of combining RT with ICIs in producing significant and long-lasting clinical responses in solid tumors, particularly in patients with lung cancer and melanoma [ [16] , [17] , [18] , [19] ].…”