4701 - Treatment-related adverse events and tolerability in patients with advanced non-squamous non-small cell lung cancer treated with first-line checkpoint inhibitors in combination with chemotherapy

Background

Non-squamous non-small cell lung cancer (NSCLC) accounts for majority of lung cancer, the second most common cancer in US. Combination of checkpoint inhibitors and chemotherapy has become a fundamental paradigm shift in the first-line treatment of advanced lung cancer. We conducted a combined analysis of randomized controlled trials (RCT) to determine the risk of treatment-related adverse events (TRAE) and treatment discontinuation due to TRAE.

Methods

PUBMED, MEDLINE, EMBASE databases and meeting abstracts from inception through March 2019 were queried. RCTs of first-line chemotherapy +/- immunotherapy in patients with advanced non-squamous NSCLC were incorporated. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) and risk difference (RD) with 95% confidence interval (CI). Random effects model was applied.

Results

A total of 2785 patients with advanced non-squamous NSCLC from 5 RCTs were included. The study arm used standard chemotherapy regimens in combination with pembrolizumab or atezolizumab while control arm used only standard chemotherapy regimens. The randomization ratio was 2:1 in IMpower-130 and Keynote-189 studies and 1:1 in other studies. The pooled RR of any-grade TRAE was 1.02 (95% CI: 0.99 –1.04, P = 0.20) and RR of high-grade TRAE was significant at 1.20 (95% CI: 1.07 –1.34, P = 0.002). Treatment-related deaths were 58 (3.57%) in study arm vs 31 (2.66%) in control arm. The pooled RR was not statistically significant at 1.26 (95% CI: 0.81 –1.95, P = 0.31) and RD was 0.01 (95% CI: - 0.00 – 0.02, P = 0.08). Treatment discontinuation due to TRAE was noted in 440 (27.14%) vs 235 (20.19%) in control group with RR of 1.35 (95% CI: 1.15 –1.59, P = 0.0003) and RD of 0.07 (95% CI: 0.03 – 0.11, P = 0.001).

Conclusions

Patients on upfront combined chemoimmunotherapy experienced high-grade TRAE, ultimately leading to treatment discontinuation. Yet, there were no significant increase in the risk of treatment related deaths due to TRAE, compared to standard chemotherapy. Pre-emptive measures with proper supportive care may enhance patients’ quality of life and compliance.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Kyaw Zin Thein.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.