Stereotactic body radiotherapy (SBRT) did not improve the efficacy of nivolumab plus ipilimumab (nivo-ipi) in patients with advanced Merkel cell carcinoma in a phase 2 study. 

Patients who had not received prior treatment with an immune checkpoint inhibitor (ICI) had an overall response rate (ORR) of 100% with nivo-ipi alone or nivo-ipi in combination with SBRT. 

Among patients who had received prior ICI treatment, the ORRs with nivo-ipi, alone or in combination with SBRT, were much lower. 

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These results were presented at ESMO Congress 2022 by Sungjune Kim, MD, PhD, of Moffitt Cancer Center in Tampa, Florida, and published in The Lancet.1,2

The phase 2 study (ClinicalTrials.gov Identifier: NCT03071406) included 50 patients with recurrent or metastatic Merkel cell carcinoma. Patients had to have at least 2 distinct lesions and could not have active brain metastasis.

The patients were randomly assigned to receive nivolumab at 240 mg every 2 weeks plus ipilimumab at 1 mg/kg every 6 weeks (n=25) or the same dosing schedule of nivolumab-ipilimumab plus SBRT (24 Gy in 3 fractions at week 2). Patients were treated until disease progression, unacceptable toxicity, or consent withdrawal.

Baseline characteristics were similar between the treatment arms. In the overall cohort, the median age was 73 (interquartile range, 67-81) years, 78% of patients were men, and all were White. About half of patients (48%) were ICI-naïve, and 90% were chemotherapy-naive.

The median follow-up was 14.6 months. SBRT did not improve ORR, duration of response (DOR), progression-free survival (PFS), or overall survival (OS). However, all of these outcomes were superior in patients who were ICI-naïve at baseline, compared with patients who had prior ICI exposure. Details can be seen in the table below.

Outcomes

Nivo-Ipi Alone (n=25)

Nivo-Ipi + SBRT (n=25)

 

ICI naïve (n=13)

Prior ICI (n=12)

ICI naïve (n=11)

Prior ICI (n=14)

ORR

100%

42%

100%

21%

Median DOR

Not reached

15 months

Not reached

5 months

Median PFS

Not reached

4.2 months

Not reached

2.7 months

Median OS

Not reached

14.9 months

Not reached

9.7 months

 

“Longer-term follow-up will be necessary for an accurate representation of the survival outcomes,” Dr Kim noted. 

The rate of grade 1-2 adverse events (AEs) was 44% in the nivo-ipi alone arm and 64% in the SBRT arm. The rate of grade 3 AEs was 28% and 24%, respectively. The rate of grade 4 AEs was 12% and 8%, respectively.

Disclosures: This research was supported by Bristol Myers Squibb. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of disclosures.

References

  1. Kim S, Wuthrick E, Blakaj DM, et al. Combined nivolumab and ipilimumab with or without stereotactic body radiation therapy for advanced Merkel cell carcinoma. Presented at ESMO 2022; September 9-13, 2022. Abstract LBA42.
  2. Kim S, Wuthrick E, Blakaj DM, et al. Combined nivolumab and ipilimumab with or without stereotactic body radiation therapy for advanced Merkel cell carcinoma: A randomised, open label, phase 2 trial. Lancet. Published online September 11, 2022. doi:10.1016/S0140-6736(22)01659-2

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ESMO 2022 Merkel Cell Carcinoma Skin Cancer