Abstract 106P
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.
Resources from the same session
88P - Utilisation of the ESMO-MCBS in prioritising immune-checkpoint inhibitors for a WHO model list of essential medicines application
Presenter: Mario Csenar
Session: Poster Display session
Resources:
Abstract
89P - Safety and efficacy of rechallenge with immune checkpoint inhibitors in advanced solid tumor: A systematic review and meta-analysis
Presenter: Huijun Xu
Session: Poster Display session
Resources:
Abstract
90P - Meta-analysis of hypophysitis incidence in melanoma patients treated with immune checkpoint inhibitors
Presenter: Vincas Urbonas
Session: Poster Display session
Resources:
Abstract
91P - Territorial disparities in the use of hospitalization at home for immune checkpoint inhibitors infusion in France between 2021 and 2022
Presenter: Anne Claire Toffart
Session: Poster Display session
Resources:
Abstract
92P - An investigation on the differences between the pre-treatment nutritional and immunological status of nasopharyngeal carcinoma patients and the healthy population
Presenter: Qiao He
Session: Poster Display session
Resources:
Abstract
93P - Pseudoprogression in immunotherapy: Illusion or reality? P-PIT study
Presenter: Amelie Toulet
Session: Poster Display session
Resources:
Abstract
94P - Real-world characteristics, treatments and healthcare recourse utilization (HCRU) of patients (pts) with advanced/metastatic non-small cell lung cancer (mNSCLC) managed with first line (1L) immuno-oncology (IO) strategies in Greece: The IO-HORIZON study
Presenter: Dimitrios Ziogas
Session: Poster Display session
Resources:
Abstract
95P - Quality of life (QoL) and care pathway in patients with durable response to immune checkpoint inhibitors (ICI-DR) for advanced or metastatic non-small cell lung cancer (NSCLC) or melanoma: QUALICI study
Presenter: Nicolas Girard
Session: Poster Display session
Resources:
Abstract
96P - Comparative cardiovascular risks of PD-1 vs. PD-L1 inhibitors: A meta-analysis of incidence and severity of cardiotoxicity
Presenter: Mohammedbaqer Al-Ghuraibawi
Session: Poster Display session
Resources:
Abstract
97P - Cardiac risk stratification and serial monitoring during immune checkpoint inhibitor therapy: Prospective real-world experience
Presenter: James Knott
Session: Poster Display session
Resources:
Abstract