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Primary Ipilimumab / Nivolumab immunotherapy followed by adjuvant Nivolumab in locally advanced or oligometastatic melanoma: preliminary results

The aim of neo-adjuvant therapy in locally advanced or oligometastatic melanoma is to facilitate radical resection, improve outcomes and undertake research to identify biomarkers of response and resistance.
Recently, pathological response has been indicated as a surrogate of survival.

Researchers have investigated the efficacy of Ipilimumab ( Yervoy ) / Nivolumab ( Opdivo ) combination as primary treatment of locally advanced or oligometastatic melanoma patients, within an open label, single arm, two centres study.

Treatment schedule consisted of 4 neoadjuvant cycles of Ipilimumab 1 mg/kg and Nivolumab 3 mg/kg every 3 weeks, followed by surgery and adjuvant Nivolumab 480 mg every 4 weeks for 6 cycles.

Primary objective is pathological complete remission ( pCR ) rate. Secondary objectives were: safety, feasibility and efficacy; health related quality of life; identification of molecular and immunological biomarkers of response and resistance ( somatic genetic drivers, tumor mutational burden [ TMB ], mutational signatures, predicted neoantigens, germline HLA typing, somatic HLA mutations and liquid biopsy ); degree of immune activation; evaluation of microbioma.

From March 2019, 26 out of 35 patients were enrolled. In the ITT population ( 22 patients ), 21 patients were stage III and 1 stage IV-M1b cutaneous melanoma; 17 patients concluded neoadjuvant therapy and received surgery; 4 patients concluded the adjuvant treatment.

Pathologic complete response ( pCR ) was reached in 9/17 ( 52% ), pathological partial remission in 4/17 ( 24% ) and pathological no response ( pNR ) in 4/17 ( 24% ) patients.

With a median follow-up of 5 months, all patients are alive; one, with pNR at surgery, relapsed during adjuvant phase.

In the neoadjuvant phase 4 patients ( 18% ) developed G3-4 adverse events: 2 transaminitis, 1 myocarditis and 1 asyntomatic CPK increase after 4, 3 and 2 cycles; 3 of them underwent to surgery after toxicity resolution.
No G3-4 adverse events were observed during adjuvant phase.

In conclusion, primary Ipilimumab / Nivolumab is effective and feasible, showing high pCR rate. Toxicity was superimposable to that already observed with this schedule.
Longer follow-up is needed to assess a correlation between pathological response and survival. ( Xagena )

Source: European Society for Medical Oncology ( ESMO ) Virtual Meeting, 2020