106P - Immunotherapy after progression to double immunotherapy: Pembrolizumab and Lenvatinib versus conventional chemotherapy for patients with metastatic melanoma after failure of PD-1/CTLA-4 inhibition

Background

PD-1 inhibition as monotherapy following by CTLA-4 inhibition at progression or as upfront double co-inhibition have drastically improved the outcomes of metastatic melanoma. Still many patients develop resistance to both ICIs and relapse soon, having conventional chemotherapy(CC) as the only therapeutic option. The phase II LEAP-004 trial supported that pembrolizumab/lenvatinib could potentially overcome anti-PD-1/anti-CTLA-4 immunotherapy refractoriness.

Methods

In the absence of any prospective study and to evaluate in a real-world context the clinical benefit of LEAP-004-proposed combination, we conducted here a retrospective comparison of pembrolizumab(200mg Q3W)with lenvatinib(at a reduced dose 10mg OD due to its known toxicity)with CC(carboplatin 4AUC and dacarbazine 850mg/m² Q3W)in this frail population of unmet need who relapsed to both ICIs, either in combinatorial or in sequential setting. Baseline demographics, disease characteristics as well as treatment outcomes(ORR, PFS and OS)and safety profile were recorded.

Results

A total of 84 patients were included in the effectiveness and safety analysis (pembro/lenva, n=39 and CC, n=45). Median age was 67 vs .64 years and males were 33.3% vs .46.7%, respectively. The distribution of metastases was comparable, including 12.8% vs .20% with brain involvement. Most patients had PS<2 (69.9% vs .56.5%),increased LDH (71.8% vs .84.4%), BRAF-wild status (82.1% vs .84.8%) and received>=2 previous therapies (61.5% vs .53.3%). The median follow-up was 18 months. The ORR was 23.1% vs .11.1% (P<0.0001), the median PFS was 4.8 vs. 3.8 months (HR [95%CI]: 0.57 [0.36-0.92]; P=0.017) and the median OS was 14.2 vs .7.8 months (HR [95%CI]: 0.39 [0.22-0.69], P=0.0009), in pembro/lenva and CC arms, respectively. Grade 3-5 treatment-related AEs were documented in 48.7% vs. 75.6% of patients (P=0.034), led to treatment discontinuation in 10.3% vs. 17.8% of cases, respectively.

Conclusions

This is the first comparative study in patients with metastatic melanoma refractory to PD-1/CTLA-4 inhibition and showed significantly better outcomes in cases treated with pembro/lenva versus CC.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

D. Ziogas: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, BMS, Ipsen, Pierre Fabre, Gilead, Amgen; Financial Interests, Personal, Advisory Board: Roche. M. Liontos: Financial Interests, Personal, Advisory Board: Astra Zeneca, GSK, Janssen, MSD, Pfizer, Bayer, Novartis; Financial Interests, Personal, Invited Speaker: Astellas. H. Gogas: Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre, Sanofi; Financial Interests, Personal, Invited Speaker: MSD, BMS, Novartis, Pierre Fabre, Sanofi; Financial Interests, Personal, Steering Committee Member: Amgen, Replimune; Financial Interests, Institutional, Local PI: Amgen, MSD, BMS, Replimune, Iovance, Bayer; Financial Interests, Institutional, Research Grant: MSD, Pfizer, Lilly, Pierre Fabre, Astra Zeneca. All other authors have declared no conflicts of interest.