1288P - Neoadjuvant therapy with anti-PD-1/PD-L1 plus platinum-base chemotherapy for resectable stage II-III non-small cell lung cancer: A systematic review and meta-analysis of randomized clinical trials

Background

Neoadjuvant chemotherapy (CT) has limited benefit over surgery alone for resectable non-small cell lung cancer (NSCLC). Recent trials have shown promising results for combining immune checkpoint inhibitors with platinum-doublet chemotherapy (ICI plus CT).

Methods

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) that compared neoadjuvant ICI plus CT versus CT alone in patients with resectable NSCLC. We searched PubMed, Scopus, and Cochrane Library databases, as well as the ASCO, ESMO, and AACR websites. We used a fixed effects model for analysis and assessed heterogeneity with I² statistics.

Results

We included six RCTs with 2,471 patients, of whom 75% were male, 47% had non-squamous, and 53% had squamous cell carcinoma (SCC). The median age was 63.3 years (ranged from 29 to 88). After neoadjuvant therapy, 84% of patients in the ICI plus CT group underwent surgery compared to 81% in the CT group (p=0.16); R0 resection was reported in 78% versus 67% of patients (p<0.01), respectively. We found a significantly higher pathologic complete response (risk ratio [RR] 5.81 [95%CI 4.26-7.92]) and major pathologic response (RR 3.57 [3.09-4.55]) in patients who received ICI plus CT than those in the CT group. Treatment with ICI plus CT provided a greater benefit of event-free survival (EFS) (HR 0.59 95%CI 0.51-0.67 p<0.00001) and overall survival (HR 0.66 95%CI 0.53-0.82 p=0.0002)compared to CT alone. ICI plus CT improved EFS regardless of PD-L1 expression, type of platinum CT, or histology. Patients with PD-L1 ≥1% achieved considerably better EFS than those with PD-L1 <1% (HR 0.40 vs 0.76, p<0.0001). Subgroup analysis showed EFS benefit for all stages (IB and II, IIIA, and IIIB). Treatment-related adverse events grades 3 or 4 were seen in 36% of patients in the intervention arm and 32% of the control arm (p=0.05).

Conclusions

Neoadjuvant therapy with anti-PD-1/PD-L1 plus CT provided significantly higher pathologic response, EFS, and OS compared to CT alone for resectable stage II-III NSCLC patients. More mature data from the trials are awaited to confirm these findings.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.