Guggina LM et al.  Oncol Ther 2017; 5: 135. doi:10.1007/s40487-017-0050-6

And even though immune checkpoint inhibitors are beneficial, they “do not result in marked absolute overall survival improvements in this population, leaving room for much efficacy improvement,” continue Hazel O’Sullivan (Cork University Hospital, Ireland) and Sanjay Popat (Institute of Cancer Research, London, UK).

Specifically, the cemiplimab–chemotherapy combination is indicated for adults with a tumoral PD-L1 expression level of at least 1% who do not harbor EGFR , ALK , or ROS1 alterations and who have locally advanced NSCLC not suitable for definitive chemoradiation or metastatic disease.

The team therefore believes that “the current analysis further [supports] the use of camrelizumab plus carboplatin and pemetrexed in [the] first-line treatment of advanced NSCLC without EGFR/ALK alterations.”

Phase 1b trial findings indicate that telisotuzumab vedotin, given in combination with erlotinib, may have potential as a treatment option for progressing EGFR mutation-positive non-small-cell lung cancer with c-Met overexpression.

However, similar to their EGFR counterparts, HER2 inhibitors also have evidence of toxicity in clinical studies.

The CHOICE-01 trial enrolled 465 individuals with treatment-naïve locally advanced or metastatic NSCLC lacking EGFR or ALK alterations and randomly assigned them to receive intravenous toripalimab 240 mg or placebo every 3 weeks alongside four to six cycles of chemotherapy, consisting of nab-paclitaxel plus carboplatin for squamous disease and pemetrexed plus cisplatin or carboplatin for nonsquamous disease.

Extended follow-up data from the ADAURA trial show that the disease-free survival benefit with adjuvant osimertinib over placebo continues beyond the 3-year treatment duration in people with EGFR -mutated stage IB–IIIA non-small-cell lung cancer.

The sensitivity of the selective tyrosine kinase inhibitor poziotinib in people with advanced non-small-cell lung cancer and EGFR exon 20 insertions is “highly dependent” on the location of the insertion, US researchers have found.

For example, KRAS mutations were associated with resistance to EGFR inhibitors in advanced NSCLC, with a significant gene-by-treatment hazard ratio (HR) for death of 1.86.

Baseline PD-L1 expression or tissue EGFR or ALK mutation status were not significantly associated with NLR, but the investigators note that the differential effect that a high NLR had on OS between the two treatments was magnified when EGFR- or ALK -positive patients were excluded from the analysis.

Individuals with non-small-cell lung cancer harboring uncommon or very rare EGFR mutations benefit from treatment with EGFR–tyrosine kinase inhibitors, but those with exon 20 insertions do not, German research suggests.

High tumor mutational burden is associated with a better response to immune checkpoint inhibitors in people with non-small-cell lung cancer across all levels of PD-L1 expression, US researchers report.

First-line treatment with the third-generation EGFR–tyrosine kinase inhibitor aumolertinib significantly improves progression-free survival relative to gefitinib in people with advanced non-small-cell lung cancer and sensitizing EGFR mutations, indicate Chinese trial data.

And we were doing PCR to look at KRAS, to look at EGFR, and then we had new biomarkers coming.

Authors: Ana Ortega-Franco & Shereen Rafee Abstract The introduction of tyrosine kinase inhibitors (TKI) for the treatment of metastatic non-small cell lung cancer (NSCLC) harbouring sensitizing epidermal growth factor receptor (EGFR) gene mutations revolutionized the diagnostic and treatment algorithm of this subset of patients almost two decades ago.

DOI [Teaser] Key Summary Points Treatment with immune checkpoint inhibitors is generally poorly effective for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients who experience acquired resistance to an EGFR-tyrosine kinase inhibitor (TKI).

A post-hoc analysis of a randomized trial points to the benefit of adding metformin to an EGFR–tyrosine kinase inhibitor in advanced non-small-cell lung cancer patients with a BMI of at least 24 kg/m 2 .

GEMSTONE-302: Sugemalimab plus chemotherapy for stage IV NSCLC This double-blind, phase 3 study was also conducted in China and enrolled 479 individuals with treatment-naïve, stage IV squamous or nonsquamous NSCLC without known EGFR sensitizing mutations, or ALK , ROS1 , or RET fusions.

People with EGFR -positive non-small-cell lung cancer may benefit from individualized risk-profiling, say researchers who observed a high recurrence risk following resection but also identified a subgroup that may be cured without adjuvant osimertinib.