338P - Anti PD1 is superior to anti PDL1 when combined with chemotherapy in first-line treatment for metastatic non-small cell lung cancer (mNSCLC): A network meta-analysis

Background

Platinum based chemotherapy (CT) with anti PD1/PDL1 is now a standard first line therapy in the management of mNSCLC without targetable driver mutations. PDL1 is expressed on tumour cells and PD1 is expressed on immune cells and these alternate mechanisms may alter clinical outcomes after tumour cell death. A network meta-analysis (NWM) showed anti PD1 + CT was superior to anti PDL1 + CT in overall survival (OS). However, only one anti PDL1, atezolizumab, was included in the analysis. More recently, several randomised controlled trials (RCT) involving newer anti PD1/PD L1 agents have been reported. In the absence of a head-to-head trial between anti PD1 and anti PD1, we performed an updated NWM which is the first to involve multiple anti PDL1 agents to assess a drug class effect. Furthermore, a second NWM for first line anti PD1/PDL1 monotherapy (MT) was performed to evaluate the effect of CT on PD1/PDL1 biology. These findings will guide future therapies in mNSCLC.

Methods

A systematic literature review of RCTs in the first line mNSCLC, comparing anti PD1/PDL1 alone or in combination with CT was performed. Indirect comparison between anti PD1 and anti PDL1 was performed using NWM, in accordance with PRISMA guidelines. OS was analysed and reported using Bayesian fractional polynomial random-effects models.

Results

Twenty-three trials were identified. Heterogeneity and risk of bias were generally low across trials. Indirect comparison showed OS favours anti PD1 + CT (HR, 0.80; 95% CI, 0.68-0.95) compared to anti PDL1 + CT. There was no difference between anti PD1 versus anti PDL1 MT (HR, 0.95; 95% CI, 0.74-1.23).

Conclusions

Here we demonstrate that anti PD1 + CT is superior to PDL1 + CT in first line mNSCLC treatment, in keeping with earlier reports. The inferior outcome for anti PDL1 was previously attributed to the activity of unblocked PDL2. However, no difference was observed for anti PD1/PDL1 MT. This suggests that CT may alter the immune biology to favour PD1 blockade rather than the mere presence of PDL2. Future concurrent chemoimmunotherapy trials should involve anti PD1 and not anti PDL1 to achieve superior anti-tumour efficacy.

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.