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
4900 - Molecular profiling and prognostic significance of TP53 mutations in Diffuse Large B Cell Lymphoma: identifying a high-risk subgroup
Presenter: Yuan-Kai Shi
Session: Poster Display session 3
Resources:
Abstract
3809 - Differential expression of various miRNAs in Pediatric Cytogenetically Normal Acute Myeloid Leukemia (CN-AML)
Presenter: Vikas Gaur
Session: Poster Display session 3
Resources:
Abstract
4750 - Circulating tumour cells in head and neck and non-small cell lung cancer
Presenter: Kenneth O'Byrne
Session: Poster Display session 3
Resources:
Abstract
3704 - OX40/OX40L protein expression in Non-small cell lung cancer and its role in clinical outcome and relationships with other immune biomarkers
Presenter: Xiaoshen Zhang
Session: Poster Display session 3
Resources:
Abstract
2235 - Effect of Serum Survivin on Survival among Non-Small Cell Lung Cancer Patients; NCI Experience
Presenter: Reham Rashed
Session: Poster Display session 3
Resources:
Abstract
2788 - Enhanced performance of prognostic estimation from TCGA RNAseq data using transfer learning.
Presenter: Helene Vanacker
Session: Poster Display session 3
Resources:
Abstract
4689 - Analysis of Circulating Tumor DNA for Early Relapse Detection in Stage III Colorectal Cancer After Adjuvant Chemotherapy
Presenter: Samuel Jacobs
Session: Poster Display session 3
Resources:
Abstract
1454 - Ascites-derived circulating microRNAs as potential diagnostic biomarkers of gastric cancer-associated malignant ascites
Presenter: Hye Sook Han
Session: Poster Display session 3
Resources:
Abstract
5574 - Results from TRIO030, a Pre-Surgical Tissue-Acquisition Study to Evaluate Molecular Alterations in Human Breast Cancer Tissue Following Short-Term Exposure to the Androgen Receptor Antagonist Darolutamide
Presenter: Hsiao-Wang Chen
Session: Poster Display session 3
Resources:
Abstract
1787 - JMJD2A is a novel epigenetic factor of chemotherapeutic susceptibility in gastric cancer
Presenter: Yasushi Sato
Session: Poster Display session 3
Resources:
Abstract