EGFR+ Lung Cancer

Adding PARP or CHK1 inhibitors to immunotherapies for the treatment of small cell lung cancer is the next step in the pipeline of novel combination approaches, according to Charles M. Rudin, MD, PhD, in a presentation at the <em>20th Annual </em>International Lung Cancer Congress.

Investigators have identified tumor mutational burden as a promising biomarker for predicting immunotherapy responses in patients with advanced stages of non&ndash;small cell lung cancer, but is it ready for clinical application?

Paul A. Bunn, Jr., MD, discusses subsets of patients with lung cancer that can benefit more from enrolling on clinical trials with immunotherapy compared with patients who do not benefit as much from immunotherapeutic approaches. Immunotherapy does not work in every patient, Bunn notes.

Three clinical trials presented at the 2019 ESMO Congress show that the tropomyosin receptor kinase&nbsp;inhibitor larotrectinib continues to show anti-tumor activity, including long-lasting objective responses and low toxicity, according to results from an integrated analysis.

Median overall survival was improved by 6.8 months with osimertinib as a first-line treatment for patients with&nbsp;metastatic, <em>EGFR</em>-mutant non&ndash;small cell lung cancer compared with erlotinib or gefitinib, despite crossover between arms, according to updated data from the phase III FLAURA study presented at the 2019 ESMO Congress.

A final analysis of part 1 of the phase III CheckMate 227 trial showed that nivolumab plus ipilimumab led to survival benefits in previously untreated patients with advanced non&ndash;small cell lung cancer, regardless of PD-L1 expression status.

Single-agent atezolizumab improved overall survival in newly diagnosed patients with&nbsp;wild-type non&ndash;small cell lung cancer who had &ge;50% expression of PD-L1 on tumor cells or &ge;10% expression on tumor-infiltrating immune cells compared with platinum-based chemotherapy, according to the interim survival analysis of the phase III IMpower110 study.

In an interview with&nbsp;Targeted Oncology, Tetsuya Mitsudomi, MD, summarized the major areas under investigation for the treatment of patients with lung cancer and highlighted key findings from the updated 5-year data of the KEYNOTE-001 trial.

In an interview with <em>Targeted Oncology</em>, Dean A. Fennell, MD, PhD, explained the need for the MIST trial and personalized treatment for patients with mesothelioma.

In his presentation on translational research in non&ndash;small cell lung cancer during the <em>20th Annual </em>International Lung Cancer Congress&reg;, Scagliotti, a professor of oncology at the University of Torino in Italy, discussed the promising evolution of therapeutic options, pointing to steps being taken to create a larger precision medicine ecosystem.&nbsp;

Based on findings from retrospective analyses and clinical trial data, patients with <em>ALK</em>-rearranged non&ndash;small cell lung cancer may be able to receive sequential ALK inhibitors following progression with similar second and third-generation agents.

Patients with non&ndash;small cell lung cancer on radiotherapy had a worse overall survival when a hurricane disaster was declared for their hospital than patients who did not experience a declaration, according to a study published in<em> JAMA</em>.

A matched retrospective comparison showed that progression-free survival&nbsp; in patients with advanced non-small cell lung cancer and actionable mutations was similar whether treatment went was guided with the use of tissue or circulating tumor DNA analysis with the Guardant360 assay.

Relapsed ALK-Rearranged NSCLC

In an interview with <em>Targeted Oncology</em>, John V. Heymach, MD, PhD, discussed the phase II study to identify mechanisms of acquired poziotinib resistance and the other available agents for targeting <em>EGFR</em> exon 20&ndash;mutant NSCLC.

In an interview with <em>Targeted Oncology</em>, Yi-Long Wu, MD discussed the results of the INSIGHT study and other agents and combinations for the treatment of patients with <em>EGFR</em>-mutant NSCLC.<br /> &nbsp;

Kazuhiko Nakagawa, MD, PhD, discusses the role of EGFR tyrosine kinase inhibitors for the frontline treatment of patients with&nbsp;<em>EGFR</em>-positive non&ndash;small cell lung cancer.

Atezolizumab monotherapy demonstrated a statistically significant overall survival benefit in comparison with chemotherapy doublets in patients with untreated advanced non&ndash;small cell lung cancer with high PD-L1 expression and without <em>ALK </em>or <em>EGFR </em>mutations. This met the primary endpoint for the phase III IMpower110 trial, according to initial results release by Genentech, the developer of the PD-L1 inhibitor.

The combination of&nbsp;atezolizumab plus carboplatin and nab-paclitaxel demonstrated a clinical overall survival benefit in a subgroup of patients with&nbsp;advanced squamous non&ndash;small cell lung cancer and a high level of PD-L1 expression in the phase III IMpower131 trial. Final data for this study was presented at the 2019 World Conference on Lung Cancer.

The FDA has granted a breakthrough therapy designation to tepotinib, an investigational MET inhibitor, for the treatment of patients with metastatic non&ndash;small cell lung cancer harboring a&nbsp;MET&nbsp;exon 14 skipping alteration who have progressed following platinum-based therapy.

Treatment with selpercatinib induced responses in 68% of patients with&nbsp;<em>RET&nbsp;</em>fusion&ndash;positive non&ndash;small cell lung cancer, according to findings from the phase I/II LIBRETTO-001 trial.

Bemcentinib, a first-in-class AXL inhibitor, in combination with the PD-1 inhibitor&nbsp;pembrolizumab showed activity in patients with immunotherapy-naive&nbsp;advanced&nbsp;non&ndash;small cell lung cancer, according to findings from the phase II study presented at the 2019 World Conference on Lung Cancer.

A statistically significant improvement in overall survival was demonstrated with durvalumab, a PD-L1 inhibitor, combined with chemotherapy in patients with previously untreated extensive-stage small cell lung cancer, according to findings from the phase III CASPIAN trial, presented at the 2019 World Conference on Lung Cancer.