Abstract 3612
Background
Combination of ICIs and chemotherapy (ICI-C) has become a more favourable design in recent trials. We have previously reported 6-month PFS rate (PFS6) is a good surrogate for 12-month overall survival rate (OS12) within treatment (ICI) arms, but had limited data to examine surrogate endpoints for treatment comparisons. We extend our work to validate prior findings by updating with data from more recent randomized controlled trials (RCTs), especially studies testing combination ICI-C.
Methods
We performed a literature search to identify eligible Phase (Ph) 2 and 3 RCTs of ICI. We excluded studies with sample size of < 100 or control arms without active treatment. Efficacy data including objective response rate (ORR), PFS, OS, PFS6 and OS12 were extracted. We examined the associations of relative treatment comparisons between ORR risk ratio (RR) with hazard ratios (HRs) for PFS and OS. We also studied the correlations between ORR, PFS6 and OS12 within ICI arm. A correlation coefficient (r) of 0 indicates lack of association whereas 1 implies perfect surrogacy.
Results
Forty-six RCTs (5 Ph2; 41 Ph3) with 51 treatment comparisons were identified. Associations between ORR RR with PFS HR, ORR RR with OS HR, and PFS HR with OS HR were r = 0.67, r = 0.42 and r = 0.52 respectively. For the 16 RCTs of ICI-C, these associations were r = 0.79, r = 0.58 and r = 0.64 respectively. For the 35 RCTs of ICI monotherapy, these associations were r = 0.71, r = 0.40 and r = 0.54. Within the ICI arms, associations between ORR and PFS6, ORR and OS12, and PFS6 and OS12 were r = 0.67, r = 0.54 and r = 0.79. Within ICI-C trials, these associations were r = 0.60, r = 0.56 and r = 0.60 respectively. Within ICI monotherapy trials, these associations were r = 0.51, r = 0.46 and r = 0.80 respectively.
Conclusions
In treatment comparison, the correlation between PFS and OS was modest, but stronger in ICI-C trials. Within ICI arms, PFS6 had stronger correlation with OS12 than ORR. PFS is recommended as a surrogate endpoint for ICI trials over ORR.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M. Friedlander: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Lecturer fees: AstraZeneca; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Takeda. All other authors have declared no conflicts of interest.
Resources from the same session
3252 - Genes involved in DNA replication, chromatin remodeling and cell cycle as potential biomarkers for therapy outcome to immune therapy in patients with metastatic cutaneous malignant melanoma
Presenter: Fernanda Costa Svedman
Session: Poster Display session 3
Resources:
Abstract
5545 - Phase Ib/II Study (SENSITIZE) assessing safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical outcome of domatinostat in combination with pembrolizumab in patients with advanced melanoma refractory/non-responding to prior checkpoint inhibitor therapy
Presenter: Jessica Hassel
Session: Poster Display session 3
Resources:
Abstract
5213 - Genomic landscape of primary malignant melanoma of esophagus
Presenter: Jie Dai
Session: Poster Display session 3
Resources:
Abstract
2716 - A phase III, randomised, double-blind study of adjuvant cemiplimab versus placebo post-surgery and radiation in patients with high-risk cutaneous squamous cell carcinoma (CSCC)
Presenter: Danny Rischin
Session: Poster Display session 3
Resources:
Abstract
3550 - ILLUMINATE 301: A randomized phase 3 study of tilsotolimod in combination with ipilimumab compared with ipilimumab alone in patients with advanced melanoma following progression on or after anti-PD-1 therapy
Presenter: Marcus Butler
Session: Poster Display session 3
Resources:
Abstract
1645 - PRIME002 - Early phase II study of Azacitidine and Carboplatin priming for Avelumab in patients with advanced melanoma who are resistant to immunotherapy
Presenter: Andre Van Der Westhuizen
Session: Poster Display session 3
Resources:
Abstract
4440 - Pembrolizumab (pembro) Plus Lenvatinib (len) for First-Line Treatment of patients (pts) With Advanced Melanoma: Phase 3 LEAP-003 Study
Presenter: Alexander Eggermont
Session: Poster Display session 3
Resources:
Abstract
3454 - Proof of concept study with the histone deacetylase inhibitor vorinostat in patients with resistant BRAFV600 mutated advanced melanoma
Presenter: Sanne Huijberts
Session: Poster Display session 3
Resources:
Abstract
1832 - A phase Ia/Ib clinical study to evaluate the safety, pharmacokinetics (PK) and preliminary anti-tumor activity of FCN-159 in patients with advanced melanoma harboring NRAS-aberrant (Ia) and NRAS-mutation (Ib).
Presenter: Lu Si
Session: Poster Display session 3
Resources:
Abstract
3996 - A Phase I Clinical Trial Investigating the Therapeutic Cancer Vaccine UV1 in Combination with Pembrolizumab as First-Line Treatment of Patients with Malignant Melanoma
Presenter: Sanjiv Agarwala
Session: Poster Display session 3
Resources:
Abstract