Neoadjuvant Chemoimmunotherapy for Lung Cancer – A Meta-Analysis

1. The overall survival had a significant hazard ratio (0.65) when comparing neoadjuvant chemoimmunotherapy to neoadjuvant chemotherapy.

2. Both groups had similar rates of treatment (and surgical) related adverse events.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Recent studies have shown evidence for neoadjuvant immunotherapy combined with chemotherapy in resectable NSCLC, though conflicting approvals between regions underscore the need for comprehensive meta-analyses to assess efficacy across different patient subgroups and treatment regimens. This systematic review and meta-analysis considered recent randomized control trials (RCTs) as well as non-RCTs. Endpoints of interest included event-free survival (EFS), overall survival (OS), major pathological response (MPR), pathological complete response (pCR), surgical resection rates, and safety. With regards to OS across all patients, when comparing neoadjuvant chemoimmunotherapy vs neoadjuvant chemotherapy, the HR was 0.65 (significant). The HR for OS for PD-L1 levels of 1% or greater was 0.49 (significant) however in PD-L1 levels less than 1%, the HR was 0.89 (non-significant). With regards to EFS across all patients, when comparing neoadjuvant chemoimmunotherapy vs neoadjuvant chemotherapy, the HR was 0.59 (significant). Generally, this improvement was seen across age groups, sex, and histology. EFS in stage II showed an HR 0.71 (significant) and in stage III the HR was 0.54 (significant). EFS in PD-L1 levels less than 1% showed an HR 0.74 (significant), in PD-L1 levels of 1% to 49% the HR was 0.56 (significant) and in PD-L1 50% or greater the HR was 0.40 (significant). With regards to pathological response, the relative risk (RR) for MPR was 3.42 (significant), the RR for pCR was 5.52 (significant) when comparing neoadjuvant chemoimmunotherapy vs neoadjuvant chemotherapy. The RR for undergoing surgery was 1.05 (significant), and the RR for R0 resection was 1.05 (significant). Regarding safety, there were no significant differences in the relative risk for grade 3-5 treatment (or surgical) related adverse events between both groups. The strengths of this study include its methodology and the number of patients, while the limitations include treatment variability across studies. Overall, this review found that neoadjuvant chemoimmunotherapy had improved endpoints compared to neoadjuvant chemotherapy with similar safety rates.

Click to read the study in JAMA Oncology

Relevant Reading: Neoadjuvant immunotherapy or chemoimmunotherapy in non-small cell lung cancer: a systematic review and meta-analysis.

In-Depth [systematic review and meta-analysis]: Databases MEDLINE and Embase were searched from Jan 2013 to Oct 2023, with single-arm trials and RCTs as part of the inclusion criteria. Combined radiotherapy or EGFR mutations were excluded. The search found 602 unique results, with 42 publications and 6 abstracts extracted, and a total of 5431 patients included. With regards to OS across all patients, when comparing neoadjuvant chemoimmunotherapy vs neoadjuvant chemotherapy, the HR was 0.65 (95%CI, 0.54-0.79; I² = 0%). The HR for OS for PD-L1 levels of 1% or greater was 0.49 (95%CI, 0.33-0.73; I² = 48.5%) however in PD-L1 levels less than 1%, the HR was 0.89 (95%CI, 0.66-1.19; I² = 0%). With regards to EFS across all patients, when comparing neoadjuvant chemoimmunotherapy vs neoadjuvant chemotherapy, the HR was 0.59 (95%CI, 0.52-0.67; I² = 14.9%). Generally, this improvement was seen across age groups, sex, and histology. EFS in stage II showed an HR 0.71 (95%CI, 0.55-0.92; I² = 0%) and in stage III the HR was 0.54 (95% CI, 0.48-0.62; I² = 0%). EFS in PD-L1 levels less than 1% showed an HR 0.74 (95%CI, 0.62-0.89; I² = 0%), in PD-L1 levels of 1% to 49% the HR was 0.56 (95%CI, 0.42-0.73; I² = 41.3%) and in PD-L1 50% or greater the HR was 0.40 (95%CI, 0.28-0.56; I² = 32.1%). With regards to pathological response, the relative risk (RR) for MPR was 3.42 (95%CI, 2.83-4.15; I² = 31.2%), the RR for pCR was 5.52 (95%CI, 4.25-7.15; I² = 27.4%) when comparing neoadjuvant chemoimmunotherapy vs neoadjuvant chemotherapy. The RR for undergoing surgery was 1.05 (95%CI, 1.02-1.09; I² = 31.8%), and the RR for R0 resection was 1.05 (95%CI, 1.02-1.08; I2 = 0%). Regarding safety, there were no significant differences in the relative risk for grade 3-5 treatment (or surgical) related adverse events between both groups. Generally, there was a low risk of bias among RCTs, and for non-RCTs bias concerns were mostly associated with inadequate length of follow-up. Overall, this review found that neoadjuvant chemoimmunotherapy had improved endpoints compared to neoadjuvant chemotherapy with similar safety rates.

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