Abstract 83P
Background
Early results evaluating immunotherapy (IO)-based neoadj strategies for NSCLC have been promising, with an emphasis on pathologic endpoints. Given the increasing number and variety of regimens, studies defining collective pCR rates are needed for future clinical trial design and eventual practice. Comparing these novel neoadj approaches to FDA approved chemotherapy (chemo) regimens can also provide insight into efficacy and utility.
Methods
MEDLINE and SCOPUS databases were searched to identify articles and abstracts, published before 2021/11, of prospective clinical trials reporting pCR and major pathologic response (MPR) of neoadj IO, chemo and chemo+IO regimens in resectable NSCLC. Chemo trials published after 2000, using platinum-based regimens are included. Use of neoadj radiation was excluded given potential impact on pathologic assessment. Random effect meta-analysis was conducted to estimate pooled pCR and MPR rates of each regimen, and meta-regression was used to evaluate differences in pCR between regimens, by adjusting for stage (I/II vs. III). Sensitivity analyses were conducted to assess impact of cross-study variations.
Results
Forty-one studies with a total of 2964 patients were included. There were 22 chemo, 8 IO and 11 chemo+IO trials. pCR differed between regimens with pooled rates of 6% (95% CI: 4-8%), 10% (95% CI: 4-16%) and 34% (95% CI: 24-43%), respectively. Rates of MPR were 28% (95% CI: 15-41%) and 61% (95% CI: 50-73%) for IO and chemo+IO, respectively. Meta-regression suggests no significant difference between chemo versus IO (p=0.34), while chemo+IO had the highest pCR (p < 0.0001). Using 39 trials reporting pCR by stage, stage III disease trended toward improved pCR regardless of regimen (p=0.11). Chemo+IO significantly improved pCR regardless of disease stage (p<0.0001). Similar trends were not appreciated for either IO or chemo.
Conclusions
Neoadj chemo+IO achieved highest rates of pCR, regardless of patient stage. There was a numerical difference in pCR between chemo and IO. These pooled rates provide helpful benchmarks to inform future neoadj trial design, prioritization and patient management.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
P.M. Forde: Financial Interests, Personal and Institutional, Funding, Consultant: AstraZeneca; Financial Interests, Personal and Institutional, Funding, Consultant: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Funding, Consultant: Novartis; Financial Interests, Institutional, Funding: Corvus; Financial Interests, Institutional, Funding: Kyowa; Financial Interests, Personal, Other, Consultant: Amgen; Non-Financial Interests, Personal, Advisory Board, Data and safety monitoring board member: Polaris; Non-Financial Interests, Personal, Advisory Board, Data and safety monitoring board member: Flame Therapeutics; Financial Interests, Personal, Other, Consultant: Daiichi Sankyo; Financial Interests, Personal, Other, Consultant: Iteos; Financial Interests, Personal, Other, Consultant: Janssen; Financial Interests, Personal, Other, Consultant: Mirati; Financial Interests, Personal, Other, Consultant: Sanofi. C. Hu: Financial Interests, Personal, Other, Consultant: D1Med Ltd.; Financial Interests, Institutional, Research Grant: RTOG Foundation; Financial Interests, Institutional, Research Grant: NIH/NCI. All other authors have declared no conflicts of interest.