Meta-Analysis Finds CIT Regimens Associated With Improved Survival, Safety Outcomes in NSCLC

Due to the lack of head-to-head trials comparing chemoimmunotherapy regimens with chemotherapy alone as first-line treatment for non-small cell lung cancer, researchers conducted a network meta-analysis of 17 randomized controlled trials of patients with the cancer.

A review of the available literature suggested patients with non-small cell lung cancer (NSCLC) who were first treated with chemoimmunotherapy (CIT) had superior outcomes compared with those who underwent treatment of just chemotherapy.

Due to the absence of head-to-head trials comparing CIT regimens with chemotherapy alone as first-line treatment for NSCLC, researchers conducted a network meta-analysis of 17 randomized controlled trials of patients with stage 4 high programmed death-ligand 1 (PD-L1+) NSCLC.

The analysis revealed improved survival and response rates, as well as safety outcomes were associated with certain immunotherapy and CIT regimens, such as those with pembrolizumab and atezolizumab, compared with chemotherapy alone.

“Our findings suggest that monotherapy or combination regimens with atezolizumab or pembrolizumab offer greater overall survival (OS) and objective response rate (ORR) benefits with less risk of side effects than a traditional chemotherapy regimen alone,” explained the researchers.

They continued, “our findings are confirmatory of the individual trial findings for CIT versus chemotherapy and are consistent with National Comprehensive Cancer Network (NCCC) and European Society for Medical Oncology (ESMO) recommendations for first-line treatment of patients with NSCLC and high PD-L1 expression.”

Compared with chemotherapy, atezolizumab and pembrolizumab were associated with significantly longer OS estimates (10.4 months difference and 7.2 months difference, respectively); however, this was not seen with nivolumab or nivolumab plus ipilimumab regimens.

According to the researchers, the data revealed that the treatment effect of most CIT regimens showed a delayed onset, with a superiority over chemotherapy becoming evident at approximately 9 months.

Immunotherapy alone also yielded outcome benefits, with the researchers observing improved ORRs with pembrolizumab monotherapy (odds ratio [OR) 1.55) and cemiplimab monotherapy (OR 2.55).

Notably, histology swayed whether CIT improved survival and response rates, in addition to the extent of improvement. For example, among patients with squamous histology, OS did not differ significantly based on CIT or chemotherapy treatment.

Among these patients, regimens that combined carboplatin and paclitaxel with atezolizumab were associated with improved ORR (OR 3.12), with the exception of carboplatin and paclitaxel plus atezolizumab and bevacizumab. Similarly, regimens combining carboplatin and paclitaxel with pembrolizumab were also associated with improved ORR (OR 3.07).

Meanwhile, for patients with non-squamous histology, pembrolizumab plus platinum-based chemotherapy followed by a pemetrexed regimen as maintenance treatment was associated with significantly improved survival compared with chemotherapy alone. Pembrolizumab alone was also associated with significantly improved survival compared with chemotherapy alone (hazard ratio [HR] 0.71).

Among these patients with non-squamous histology, carboplatin and paclitaxel in combination with atezolizumab (OR 2.41), pembrolizumab in combination with platinum-based chemotherapy followed by maintenance pemetrexed (OR 5.85), and sintilimab (OR 3.45) were all associated with improved response rates.

With regard to safety, the researchers found that CIT regimens with pembrolizumab and atezolizumab were associated with significantly lower risks of treatment-related adverse events compared with chemotherapy.

Reference: Herbst R, Jassem J, Abogunrin S, et al. A network meta-analysis of cancer immunotherapies versus chemotherapy for first-line treatment of patients with non-small cell lung cancer and high programmed death-ligand 1 expression. Front Oncol. Published online July 9, 2021. doi:10.3389/fonc.2021.676732