Avelumab in patients with previously treated metastatic Merkel cell carcinoma (JAVELIN Merkel 200): updated overall survival data after >5 years of follow-up

Abstract

Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer that has a poor prognosis in patients with advanced disease. Avelumab [anti-programmed death-ligand 1 (PD-L1)] became the first approved treatment for patients with metastatic MCC (mMCC), based on efficacy and safety data observed in the JAVELIN Merkel 200 trial. We report long-term overall survival (OS) data after >5 years of follow-up from the cohort of patients with mMCC whose disease had progressed after one or more prior lines of chemotherapy. Patients and methods: In Part A of the single-arm, open-label, phase II JAVELIN Merkel 200 trial, patients with mMCC that had progressed following one or more prior lines of chemotherapy received avelumab 10 mg/kg by intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxicity, or withdrawal. In this analysis, long-term OS was analyzed. Results: In total, 88 patients were treated with avelumab. At data cut-off (25 September 2020), median follow-up was 65.1 months (range 60.8-74.1 months). One patient (1.1%) remained on treatment, and an additional patient (1.1%) had reinitiated avelumab after previously discontinuing treatment. Median OS was 12.6 months [95% confidence interval (CI) 7.5-17.1 months], with a 5-year OS rate of 26% (95% CI 17% to 36%). In patients with PD-L1þ versus PD-L1À tumors, median OS was 12.9 months (95% CI 8.7-29.6 months) versus 7.3 months (95% CI 3.4-14.0 months), and the 5-year OS rate was 28% (95% CI 17% to 40%) versus 19% (95% CI 5% to 40%), respectively (HR 0.67; 95% CI 0.36-1.25). Conclusion: Avelumab monotherapy resulted in meaningful long-term OS in patients with mMCC whose disease had progressed following chemotherapy. These results further support the role of avelumab as a standard of care for patients with mMCC.

Identifying Candidates for Immunotherapy among Patients with Non-Melanoma Skin Cancer: A Review of the Potential Predictors of Response

“…It is noteworthy that a slight tendency of improved PFS and OS was shown in patients carrying PD-L1 in a pre-treatment setting and receiving pembrolizumab [ 18 ]. A similar result was found in patients with chemotherapy-refractory MCCs receiving avelumab (cohort A of JAVELIN Merkel 200 study) [ 20 , 103 ]. In addition, in a real-world study, preliminary data analysis on 6 tumoral and plasma samples suggested that serum soluble PD-1 > 3.8 ng/mL, and the presence of PD-L1 and brisk TILs on tumor samples, were associated with a longer time to treatment failure [ 106 ].…”

“…Long-term data from the JAVELIN Merkel 200 trial (part A cohort) showed a median OS of 12.6 months (95% CI 7.5–17.1 months) and a 5-year OS rate of 26% (95% CI 17% to 36%). However, considerable differences in patients with PD-L1+ versus PD-L1- tumors were documented, with a median OS of 12.9 months (95% CI 8.7–29.6 months) and a 5-year OS rate of 28% (95% CI 17% to 40%) in the former versus a median OS of 7.3 months (95% CI 3.4–14.0 months) with a 5-year OS rate of 19% (95% CI 5% to 40%) in the latter [ 103 , 104 ].…”

Stromal Factors as a Target for Immunotherapy in Melanoma and Non-Melanoma Skin Cancers

“…Since PD-L1 is expressed in tumor cells, as well as TAMs and antigen-presenting cells (APCs), to maintain the immunosuppressive microenvironment in cSCC [ 61 ], the anti-PD1 Ab cemiplimab is used for the treatment of locally advanced and metastatic cSCC [ 70 , 71 ]. The objective response rate (ORR) of cemiplimab is 44% [95% confidence interval (CI), 32–55] for locally advanced melanoma [ 4 ], whereas it is 45.2% (95% CI, 35.9% to 54.8%) for metastatic cSCC [ 70 ].…”

“…The objective response rate (ORR) of cemiplimab is 44% [95% confidence interval (CI), 32–55] for locally advanced melanoma [ 4 ], whereas it is 45.2% (95% CI, 35.9% to 54.8%) for metastatic cSCC [ 70 ]. In Merkel cell carcinoma, the anti-PD-L1 Ab avelumab significantly prolonged overall survival (OS) in a PD-L1-highly-expressing cohort [12.9 months (95% CI, 8.7–29)] compared to a low-expressing cohort [7.3 months (3.4–14.0)] [ 71 ]. Moreover, tumor site PD-L1 expression in combination with PD-1-positive cells in TILS is a prognostic factor in CAS [ 66 ].…”

Editorial: The Evolving Role of Immunotherapy in Non-Melanoma Skin Cancers

“…Moreover, in the face of a powerful immune reaction, many patients progress or do not respond to modern immunotherapy due to resistance or immunoescape mechanisms. To date, Cemiplimab for cSCCs ( 3 ) and Avelumab ( 15 ) for MCCs have been approved by European Medicines Agency (EMA); recently Food and Drug Administration (FDA) approved Cemiplimab for locally advanced Basal cell carcinoma (LaBCC) ( 16 ) and other drugs are studied through several clinical trials.…”