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
4543 - Long-term real-world (RW) outcomes in patients with advanced melanoma (MEL) treated with ipilimumab (IPI) and non-IPI therapies: IMAGE study
Presenter: Stéphane Dalle
Session: Poster Display session 3
Resources:
Abstract
4523 - Prognostic Factors for efficacy of Ipilimumab used after AntiPD1 and/or BRAF+MEK inhibitors in Melanoma Patients: an Italian Melanoma Intergroup study
Presenter: Riccardo Marconcini
Session: Poster Display session 3
Resources:
Abstract
3632 - Rechallenge with combination ipilimumab and anti-PD-1 (IPI+PD1) in metastatic melanoma after acquired resistance to IPI+PD1 immunotherapy
Presenter: Adriana Hepner
Session: Poster Display session 3
Resources:
Abstract
3732 - Clinicopathologic characteristics of immune colitis in melanoma patients treated with combination ipilimumab and anti-PD1 (IPI+PD1) and PD1 monotherapy.
Presenter: Kazi Nahar
Session: Poster Display session 3
Resources:
Abstract
5005 - Real-world outcomes of ipilimumab plus nivolumab for advanced melanoma in the Netherlands
Presenter: Michiel van Zeijl
Session: Poster Display session 3
Resources:
Abstract
5524 - Utilization of Real-World Data to Assess the Effectiveness of Immune Checkpoint Inhibitors (ICIs) in Elderly Patients with Metastatic Melanoma
Presenter: D Scott Ernst
Session: Poster Display session 3
Resources:
Abstract
5884 - Tumor mutational burden and response to PD-1 inhibitors: an analysis of 89 cases of metastatic melanoma.
Presenter: Léa Dousset
Session: Poster Display session 3
Resources:
Abstract
3120 - Increase in S100B and LDH as early outcome predictors for non-responsiveness to anti-PD-1 monotherapy in advanced melanoma.
Presenter: Elisa Rozeman
Session: Poster Display session 3
Resources:
Abstract
2157 - Immune status defined by molecular information layers predicts response to pembrolizumab treatment in advanced melanoma
Presenter: Guillermo Prado-Vázquez
Session: Poster Display session 3
Resources:
Abstract
2553 - Interim analysis of a phase Ib study of cobimetinib plus atezolizumab in patients with advanced BRAFV600 wild type melanoma progressing on prior anti-PD-L1 therapy
Presenter: Shahneen Sandhu
Session: Poster Display session 3
Resources:
Abstract