Adenocarcinoma, large cell, NSCLC NOS: Nivolumab + ipilimumab + pemetrexed + (carboplatin or cisplatin) added as an "other recommended" first-line treatment option for patients with metastatic NSCLC, PD-L1 <1%, and PS 0-1.

…the NCCN NSCLC Panel preference stratified the systemic therapy regimens and decided that first-line therapy with nivolumab/ipilimumab is "useful in certain circumstances" (eg, renal impairment) for patients with PD-L1 levels of 1% or more and is an "other recommended" first-line therapy option for patients with PD-L1 levels less than 1%.

...we report an exploratory analysis of efficacy and safety in pts with tumor PD-L1 < 1% by histology or the presence of BM....Similarly, OS was improved with NIVO + IPI + chemo vs chemo in pts with (n = 17 vs 15) or without (n = 118 vs 114) BM; median OS was 20.6 vs 6.9 mo (HR 0.28, 95% CI 0.13–0.61) and 16.4 vs 11.2 mo (HR 0.72, 95% CI 0.54–0.96), respectively.

In the first-line setting, the most effective treatments for patients with PD-L1 expressions of ≥50%, 1-49%, and <1% were atezolizumab, pembrolizumab/chemotherapy, and nivolumab/ipilimumab, respectively.

Relative to nivolumab monotherapy, an increase in progression-free survival (PFS) and overall survival (OS) for the combination of nivolumab with ipilimumab is established only in patients with low tumour PD-L1 expression.

For PFS, the HRs at 5 years of NIVO + IPI versus comparators were: 0.30 (0.08, 0.95) versus pembrolizumab + chemotherapy and 0.52 (0.17, 1.55) versus atezolizumab + bevacizumab + chemotherapy in the non-squamous population; 0.32 (0.16, 0.66) versus pembrolizumab + chemotherapy in the squamous population....This study demonstrates trends towards long-term survival benefit with NIVO + IPI compared with other IO-based combinations among patients with PD-L1 < 1%, with statistically significant improvements over atezolizumab + bevacizumab + chemotherapy in the non-squamous setting, and over pembrolizumab + chemotherapy in the squamous setting...

This single-arm, prospective phase II trial aimed to enroll 30 evaluable metastatic NSCLC patients with disease progression after chemo and anti-PD-1....In patients with both low and negative PD-L1 expressing tumors, resistant to anti-PD-1 therapy, IPI-NIVO and mRT achieved substantial tumor responses.

Subgroup analysis by PD-L1 suggested that nivolumab plus ipilimumab plus chemotherapy was associated with the best OS in patients with PD-L1 <1%...pem-chemo and nivo-ipi-chemo appear to be superior first-line immunotherapy combinations for advanced NSCLC patients with positive and negative PD-L1 expression, respectively.

A total of 9 patients were enrolled to date with 7 patients being evaluable for treatment response. Immunohistochemistry for PDL-1, performed using the FDA approved protocol for SP263 antibody on a Ventana Benchmark Ultra automatic stainer and scored on tumor cells, was <50%, >50%...There was 1 complete response, 1 partial response, 3 with stable disease…