Introducing Radiotherapy in Metastatic Merkel Cell Carcinoma Patients with Limited Progression on Avelumab: An Effective Step against Primary and Secondary Immune Resistance?

July 24, 2023


Journal of Personalized Medicine

Publication Date

July 24, 2023


Ferini, G., Zagardo, V., Critelli, P., Santacaterina, A., Sava, S., Harikar, M. M., Venkataram, T., Umana, G. E., Viola, A., Valenti, V., & Forte, S. Summary

In a recent study, researchers studied how combining radiation therapy with immunotherapy drugs like avelumab or pembrolizumab could help patients with advanced Merkel cell carcinoma (MCC) whose disease got worse despite just immunotherapy. They included eight patients with tumors suitable for radiation therapy and found that this combination treatment was effective and safe, with 60% of patients showing no recurrence at 6 months and 1 year after the radiation treatment. The overall survival rates also looked promising for up to 2 years. But it’s important to remember that this study was small and looked back at past events, rather than comparing treatment with or without radiation treatment in controlled patients’ group. More research is needed to be sure this treatment works well for all MCC patients.


Purpose: To investigate the ability of radiotherapy (RT) to prolong progression-free survival (PFS) and to report treatment-related toxicities among oligoprogressive metastatic Merkel cell carcinoma (mMCC) patients on avelumab.

Methods: We retrospectively collected clinical data on mMCC patients who underwent radiotherapy for limited progression on avelumab. Patients were categorized as primary or secondary immune refractory depending on the time of onset of resistance to immunotherapy (at the first or subsequent follow-up visits after avelumab initiation). Pre- and post-RT PFS were calculated. Overall survival (OS) from the first progression treated with RT was also reported. Radiological responses and toxicities were evaluated according to the irRECIST criteria and RTOG scoring system, respectively.

Results: Eight patients, including five females, with a median age of 75 years, met our inclusion criteria. The median gross tumor and clinical target volumes at first progression on avelumab were 29.85 cc and 236.7 cc, respectively. The treatment sites included lymph node, skin, brain, and spine metastases. Four patients received more than one course of RT. Most patients were treated with palliative radiation doses (mainly 30 Gy in 3 Gy/day fractions). Two patients were treated with stereotactic RT. Five/eight patients were primary immune refractory. The objective response rate at the first post-RT assessment was 75%, whereas no local failure was reported. The median pre-RT PFS was 3 months. The pre-RT PFS was 37.5% at 6 months and 12.5% at 1 year. The median post-RT PFS was not reached. The post-RT PFS was 60% at 6 months and 1 year. The post-RT OS was 85.7% at 1 year and 64.3% at 2 years. No relevant treatment-related toxicity was observed. After a median follow-up of 18.5 months, 6/8 patients are still alive and continuing on avelumab therapy.

Conclusions: Adding radiotherapy to mMCC patients with limited progression on avelumab seems to be safe and effective in prolonging the successful use of immunotherapy, regardless of the type of immune refractoriness.

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