Abstract 1124
Background
We previously showed that therapy with anti-CTLA-4 or anti-PD-1 agents was more effective for men as compared with women. Here we investigated whether women derive larger benefit than men from different immunotherapeutic strategies.
Methods
We performed a systematic review and a meta-analysis, including all RCTs testing anti-PD-1 or anti-PD-L1 given either alone or combined with chemotherapy in patients with advanced/metastatic solid tumors, to assess different efficacy of these two immunotherapeutic strategies according to patients’ sex. The primary endpoint of the study was to assess the difference of treatments efficacy between males and females, measured in terms of difference of the overall survival log(HR) reported in males and in females for each treatment strategy For this purpose, the pooled OS HR and 95% confidence interval (CI) was calculated in males and females using random-effects model and the heterogeneity between the two estimates was evaluated using an interaction test.
Results
16 phase III RCTs testing anti-PD1 or anti-PD-L1 in monotherapy versus standard chemotherapy in 9291 patients with advanced solid tumors were included in the analysis. Two RCTs were performed in patients with melanoma, 8 in NSCLC, 2 in HNSCC, 2 in gastric cancer, and 1 each in kidney and urothelial cancer. In 15 out of 16 of such RCTs, men derived larger OS benefit than women. The pooled-OS HR was 0.73 (95% CI, 0.69-0.78) in men versus 0.86 (95% CI, 0.78-0.94) in women (heterogeneity-p=0.0079). 5 phase III RCTs testing the combination of chemotherapy plus anti-PD-1 or anti-PD-L1 versus chemotherapy in 2979 patients were included in the analysis. Four RCTs were performed in NSCLC and 1 in SCLC. All these 5 RCTs showed impressively larger OS benefit in women. The pooled-OS HR was 0.50 (95% CI, 0.41-0.60) in women versus 0.76 (95% CI, 0.66-0.87) in men (heterogeneity p = 0.0003).
Conclusions
We confirmed a large and significant interaction between patients’ sex and the efficacy of anti-PD-1/anti-PD-L1 drugs given in monotherapy or combined with chemotherapy. The direction of such interaction was the opposite for the two immunotherapeutic strategies: women derived impressively larger benefit from the addition of chemotherapy to anti-PD1/PD-L1 as compared with men.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Fabio Conforti.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5544 - Evaluation of a radiomic signature of CD8 cells in patients treated with immunotherapy-radiotherapy in three clinical trials.
Presenter: Roger Sun
Session: Poster Display session 3
Resources:
Abstract
1117 - Biomarkers predictive of overall survival in advanced cancer patients treated with a peptide-based cancer vaccine.
Presenter: Shigetaka Suekane
Session: Poster Display session 3
Resources:
Abstract
1922 - Expression of PD-L1 in plasma exosomes of NSCLC patients and its associations with PD-L1 expression of corresponding tumor tissues
Presenter: Shaorong Yu
Session: Poster Display session 3
Resources:
Abstract
5495 - Patient’s perspective on digital biomarkers in advanced urologic malignancies
Presenter: Severin Rodler
Session: Poster Display session 3
Resources:
Abstract
3166 - A comprehensive Pan-cancer study of FGFR Aberrations in Chinese cancer patients
Presenter: Yang Gao
Session: Poster Display session 3
Resources:
Abstract
3277 - A Systemic Inflammation Response Index (SIRI) correlates with survival and could be a Predictive Factor for mFOLFIRINOX in Metastatic Pancreatic Cancer (PC)
Presenter: Vilma Pacheco-Barcia
Session: Poster Display session 3
Resources:
Abstract
2680 - Circulating biomarkers and risk of immune-related adverse events (irAEs) in patients (pts) with advanced Non-small cell lung cancer (aNSCLC) and metastatic melanoma (mMel)
Presenter: Alberto Pavan
Session: Poster Display session 3
Resources:
Abstract
4066 - Breast cancer in young women of Kazakh population depending on germline mutations: results of next-generation sequencing
Presenter: Dilyara Kaidarova
Session: Poster Display session 3
Resources:
Abstract
5514 - Discovery of an ImmunoTranscriptomics signature in blood for early colorectal cancer detection
Presenter: Paolo Angelino
Session: Poster Display session 3
Resources:
Abstract
1595 - Serum Netrin-1 as a Biomarker for Colorectal Cancer Detection
Presenter: Jinzhou Zhu
Session: Poster Display session 3
Resources:
Abstract