Abstract 1830P
Background
An early crossing of the overall survival curves in randomized clinical trials (RCTs) comparing single-agent ICI to standard treatments has been observed across different cancer types. We conducted a metanalysis to explore the association of ICI treatment with ED.
Methods
PubMed, Embase and Web of Science were searched (until 03/2021) for RCTs comparing 1st-line PD-1/PD-L1 inhibitors +/- other ICI (ICI-only group) or the same drugs in combination with other non-ICI therapies (ICI+OT group) (experimental arms) vs non-ICI treatments (control arm) in patients (pts) with advanced solid cancers. ED was defined as death within the first 3 months of treatment and studies providing the number of pts in the intention to treat-population who were alive before and after 1-3 months were included. The primary outcome was the 1-3 months ED rate both in the ICI-only and in the ICI+OT groups vs control arm. The ED rates were estimated by risk-ratio (RR) with 95% CI and pooled by random effect model. Heterogeneity was assessed by I2 statistics, risk of bias (ROB) by Cochrane tool.
Results
38 RCTs (n=27917 pts) were eligible. The majority of pts received anti-PD-1/PD-L1 monotherapy (n=3742) or ICI + chemotherapy (n=6705) in the ICI-only and ICI+OT groups, respectively. High risk of performance bias was reported in 53% of RCTs, being the most common ROB. Compared to control arm, pooled RR for the1-3 months ED rate was higher for the ICI-only group (RR: 1.22, 95% CI 0.99-1.50, p=0.06) but significantly lower for the ICI+OT group (RR: 0.81; 95% CI 0.69-0.94, p=0.005). Overall, ED risk in the first 3 months significantly increased with ICI-only treatment compared to ICI+OT (RR 1.51; 95% CI 1.16-1.95, p=0.001). Table: 1830P
| Cancer(s) | ICI-only group | ICI+OT group | ||||
| RCTs (n) | ED rate (RR, 95% CI) | I2 | RCTs (n) | ED rate (RR, 95% CI) | I2 | |
| Breast | 0 | NA | NA | 2 | 1.14 [0.51, 2.50] | 64% |
| Gastrointestinal | 3 | 1.46 [0.75, 2.83] | 80% | 5 | 0.61 [0.38, 0.96] | 74% |
| Genitourinary | 5 | 1.36 [0.69, 2.67] | 85% | 5 | 0.77 [0.60, 0.98] | 6% |
| Melanoma | 1 | 0.80 [0.49, 1.30] | NA | 2 | 0.88 [0.49, 1.55] | NA |
| Thoracic | 8 | 1.16 [0.94, 1.44] | 60% | 10 | 0.89 [0.76, 1.04] | 4% |
| All | 17 | 1.22 [0.99, 1.50] | 72% | 24 | 0.81 [0.69, 0.94] | 46% |
Conclusions
Across cancer types, ED risk is treatment specific and it is increased upon 1st-line single-agent ICI while it can be prevented by combining ICI with other non-ICI treatments.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M. Lambertini: Non-Financial Interests, Personal, Advisory Role: Roche; Non-Financial Interests, Personal, Advisory Role: AstraZeneca; Non-Financial Interests, Personal, Advisory Role: Lilly; Non-Financial Interests, Personal, Advisory Role: Novartis; Non-Financial Interests, Personal, Invited Speaker: Sandoz; Non-Financial Interests, Personal, Invited Speaker: Roche; Non-Financial Interests, Personal, Invited Speaker: Novartis; Non-Financial Interests, Personal, Invited Speaker: Takeda; Non-Financial Interests, Personal, Invited Speaker: Pfizer; Non-Financial Interests, Personal, Invited Speaker: Lilly. M. Imbimbo: Non-Financial Interests, Personal, Principal Investigator: BMS; Non-Financial Interests, Personal, Principal Investigator: Medimmune. G. Lo Russo: Financial Interests, Personal, Other, personal fees: BMS; Financial Interests, Personal, Other, personal fees: MSD; Financial Interests, Personal, Other, personal fees: AstraZeneca. C. Proto: Financial Interests, Personal, Other, personal fees: MSD; Financial Interests, Personal, Other, personal fees: BMS. A. Prelaj: Financial Interests, Personal, Other, personal fees: Roche; Financial Interests, Personal, Other, personal fees: AstraZeneca; Financial Interests, Personal, Other, personal fees: BMS. F. Morgillo: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Institutional, Research Grant: AstraZeneca. M.C.C. Garassino: Financial Interests, Personal and Institutional, Research Grant: Eli Lilly; Financial Interests, Personal and Institutional, Research Grant: Otsuka Pharma; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: Novartis; Financial Interests, Personal and Institutional, Research Grant: BMS; Financial Interests, Personal and Institutional, Research Grant: Roche; Financial Interests, Personal and Institutional, Research Grant: Pfizer; Financial Interests, Personal and Institutional, Research Grant: Celgene; Financial Interests, Personal and Institutional, Research Grant: Incyte; Financial Interests, Personal and Institutional, Research Grant: MSD; Financial Interests, Personal and Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Personal and Institutional, Research Grant: Bayer; Financial Interests, Personal and Institutional, Research Grant: Sanofi-Aventis; Financial Interests, Personal and Institutional, Research Grant: Spectrum Pharmaceuticals; Financial Interests, Personal and Institutional, Research Grant: Blueprint medicine; Financial Interests, Institutional, Research Grant: Tiziana sciences; Financial Interests, Institutional, Research Grant: Clovis; Financial Interests, Institutional, Research Grant: Merck Serono; Financial Interests, Institutional, Research Grant: Merck KGaA; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Ipsen; Financial Interests, Institutional, Research Grant: Medimmune; Financial Interests, Institutional, Research Grant: Exelixis; Financial Interests, Personal, Other, personal fees: Boehringer Ingelheim; Financial Interests, Personal, Other, personal fees: Boehringer Ingelheim; Financial Interests, Personal, Other, personal fees: Daiichi-Sankyo; Financial Interests, Personal, Other, personal fees: Takeda; Financial Interests, Personal, Other, personal fees: Seattle Genetics; Financial Interests, Personal, Other, personal fees: Mirati Therapeutics; Financial Interests, Personal, Other, personal fees: Janssen; Non-Financial Interests, Personal, Other, non-financial support: MSD; Non-Financial Interests, Personal, Other, non-financial support: Lilly. R. Ferrara: Financial Interests, Personal, Advisory Board: MSD. All other authors have declared no conflicts of interest.