Biomarker-Driven Lung Cancer

As one of the main challenges faced by cli­nicians who treat non small cell lung cancer, drug resistance continues to thwart efforts to mitigate disease progression. This is especially true for the class of drugs called tyrosine kinase inhibitors, which inhibit adenosine triphosphate at the binding site of tyrosine kinase.

A 64-Year-Old Male with Untreated Stage IV EGFR-Mutated NSCLC

The FDA has granted Priority Review to the supplemental Biologic License Application for atezolizumab as first-line treatment of patients with advanced non-squamous and squamous non-small cell lung cancer without EGFR or ALK mutations with high PD-L1 expression, as determined by PD-L1 biomarker testing. 

The FDA has granted Priority Review to the New Drug Application for lurbinectedin, which is being considered for accelerated approval as a treatment of patients with small cell lung cancer who have progressed after prior platinum-containing therapy.

Pepinemab plus avelumab has shown initial signals of antitumor activity and is well tolerated in patients with advanced non–small cell lung cancer, according to an interim analysis of the CLASSICAL-Lung phase Ib/II clinical trial presented at the 2020 American Society of Clinical Oncology-Society for Immunotherapy of Cancer Clinical Immuno-Oncology Symposium in Orlando, Florida.

The first-in-class AXL inhibitor bemcentinib plus checkpoint inhibitor pembrolizumab induced promising activity in patients with non&ndash;small cell lung cancer regardless of PD-L1 status, according to a phase II clinical trial. The data also suggest a greater benefit with the combination in patients who are AXL-positive.<br /> &nbsp;

Matthew Krebs, MBChB, PhD, explains the rationale for a phase II study of bemcentinib, a first-in-class selective AXL inhibitor, in combination with pembrolizumab in patients with advanced non&ndash;small cell lung cancer, which he presented at the 2019 Society for Immunotherapy of Cancer Annual Meeting.

The FDA granted Priority Review to the New Drug Application for capmatinib, an investigational selective MET inhibitor, which will be used as treatment for first-line and previously treated patients with locally advanced or metastatic MET exon 14 skipping-mutated non–small cell lung cancer, Incyte announced in a press release.

The FDA has granted approval to injectable pemetrexed for the treatment of patients with locally advanced or metastatic nonsquamous non&ndash;small cell lung cancer and for those with malignant pleural mesothelioma.

In an interview with&nbsp;Targeted Oncology, Justin F. Gainor, MD, discussed the significance of identifying&nbsp;RET&nbsp;alterations in patients with non-small cell lung cancer and the prevalence of this molecular target. He also highlighted data supporting further evaluation of BLU-667.

In January 2020, the FDA approved new treatment options in gastrointestinal stromal tumors, bladder cancer, and epithelioid sarcoma. The FDA also granted several Priority Review Designations, orphan drug designations, and a Fast Track designation, as well as a Breakthrough Therapy designation.

Afatinib demonstrated clinical activity against uncommon and compound <em>EGFR</em> mutations in patients with EGFR tyrosine kinase inhibitor-naive non&ndash;small cell lung cancer, a patient population for which limited data exist on the efficacy of treatment with EGFR- tyrosine kinase inhibitors, according to Yang et al.

Nasser H. Hanna, MD, discusses the key takeaways on the current role of consolidation immunotherapy in patients with lung cancer, which has become standard in this setting. He highlights questions that still need to be addressed in this space.

The addition of the dinutuximab injection to irinotecan did not improve overall survival in patients with relapsed/refractory small cell lung cancer, failing to meet the primary end point of the phase III DISTINCT trial, according to top-line results announced in a press release from United Therapeutics, developer of dinutuximab.

In a phase II trial, the combination of lenvantinib and pembrolizumab demonstrated a manageable safety profile and encouraging antitumor activity in patients with selected advanced solid tumors.&nbsp;The decision to combine the agents was based on preclinical data, which suggested that VEGF and FGF signaling may enhance the therapeutic efficacy of lenvatinib.

The New Drug Application for selpercatinib was granted FDA Priority Review for the treatment of patients with advanced&nbsp;RET&nbsp;fusion&ndash;positive non&ndash;small cell lung cancer,&nbsp;RET-mutant medullary thyroid cancer, and&nbsp;RET&nbsp;fusion&ndash;positive thyroid cancer, based on data from the phase I/II LIBRETTO-001 trial, Eli Lilly and Company announced in a press release.

Entrectinib led to clinically meaningful responses in patients with NTRK-fusion-positive solid tumors, according to results from a pooled analysis of the phase I ALKA-372-001, the phase I STARTRK-1, and the phase II STARTRK-2 studies.

Benjamin P. Levy, MD, discusses the evolution of molecular drivers in non&ndash;small cell lung cancer over the last few years and which testing should be included in patients.

Bemcentinib in combination with pembrolizumab demonstrated clinical efficacy in the stage 1 portion of a phase II trial, which evaluated the combination in patients with non&ndash;small cell lung cancer who progressed on prior immune checkpoint inhibition, meeting the primary end point of the study.

For patients with non&ndash;small cell lung cancer, having a body mass index &ge;30 at baseline could be independently associated with an improvement in overall survival with atezolizumab and could be considered a stratification factor in immune checkpoint inhibitor trials, according to a study published in JAMA Oncology.

In an interview with&nbsp;Targeted Oncology, Steven H. Kirtland, MD, FCCP, discussed the different factors that play a role in the decline of lung cancer mortality over the last few years. He highlighted how these advancements will continue to impact the survival of patients with lung cancer and his thoughts on the evolving landscape.