John V. Heymach, MD, PhD, chair, professor, and David Bruton Jr. Chair in Cancer Research, Department of Thoracic/Head and Neck Medical Oncology, professor, Department of Cancer Biology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the efficacy of mobocertinib (TAK-788) in 

 exon 20 insertion–mutated advanced non–small cell lung cancer (NSCLC). 

During the International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer, findings from an ongoing phase 1/2 study (NCT04535557) were presented and showed clinically meaningful activity with mobocertinib in patients with previously treated, metastatic NSCLC who harbor 

 exon 20 insertion mutations, says Heymach. The confirmed objective response rate was 26% per an independent review committee, and the median progression-free survival was 7.3 months. 

Although a lower incidence of skin toxicities was observed compared with other investigational drugs in this space, gastrointestinal adverse effects, including diarrhea, nausea, vomiting, decreased appetite, and stomatitis, accounted for most treatment discontinuations.

Ultimately, these findings are encouraging and represent clear evidence of activity with mobocertinib, says Heymach. Although investigators are hopeful that agents with more robust clinical efficacy will emerge in this space, mobocertinib has demonstrated improved response rates compared with first- and second-generation agents that were investigated for this subtype of metastatic NSCLC, concludes Heymach.

Videos

John V. Heymach, MD, PhD, discusses the efficacy of mobocertinib in EGFR exon 20 insertion–mutated advanced non–small cell lung cancer. 


Dr. Heymach on the Efficacy of Mobocertinib in EGFR Exon 20 Insertion–Mutated NSCLC 

John V. Heymach, MD, PhD, chair, professor, and David Bruton Jr. Chair in Cancer Research, Department of Thoracic/Head and Neck Medical Oncology, professor, Department of Cancer Biology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the potential utility of afatinib (Gilotrif) in 

 fusion–positive non–small cell lung cancer (NSCLC). 

 fusions are generated from a protein that includes a ligand for the EGFR receptor, says Heymach. Although the protein is in the EGFR family, the fusion is not driven by 

 activating mutations and is, instead, driven by persistent activity of the ligand, Heymach explains. Moreover, inhibiting HER3 is likely tied to 

 fusions because HER2 and HER3 are drivers of the alteration’s activity. Additionally, heregulin can bind to HER4, Heymach says.

As such, agents with a broader spectrum of activity may have clinical utility in 

 fusion–positive NSCLC. Afatinib, a pan-ErbB family inhibitor, has shown activity in patients with 

 fusion–positive NSCLC and may have utility as a novel treatment option in this patient population. Additionally, HER3-directed monoclonal antibodies are also being evaluated in this space, concludes Heymach.

John V. Heymach, MD, PhD, discusses the potential utility of afatinib in NRG1 fusion–positive non–small cell lung cancer.  



Dr. Heymach on the Potential Utility of Afatinib in NRG1 Fusion+ NSCLC 

John V. Heymach, MD, PhD, chairman, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, discusses the significance of nivolumab (Opdivo) for patients with lung cancer. 

The long-term follow-up for nivolumab is important for the field, states Heymach. Overall, patients in the CheckMate-026 trial saw an improvement in survival of a few months. 

The long-term data informs researchers that there are some patients that are still benefitting from the treatment years later, explains Heymach.

John V. Heymach, MD, PhD, chairman, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, discusses the significance of nivolumab (Opdivo) for patients with lung cancer.

Dr. Heymach on the Significance of Nivolumab for Lung Cancer

John V. Heymach, MD, PhD, chairman, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, discusses efficacy findings with nivolumab (Opdivo) results for patients with metastatic lung cancer.

There is now 5 years of follow-up for patients treated with nivolumab, explains Heymach. This is one of the first studies that demonstrated a positive result from immunotherapy for patients with metastatic lung cancer.

This is a significant step forward in the field, states Heymach. Patients are now becoming long-term survivors, making immunotherapy a viable treatment option.

Dr. Heymach on Nivolumab for Lung Cancer

John V. Heymach, MD, PhD, chairman, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, discusses the CheckMate-026 trial in lung cancer.

This randomized study compared frontline nivolumab (Opdivo) with chemotherapy in patients with lung cancer that had PD-L1 positivity.

Although the trial was negative, tumor mutation burden was found to be a good predictor of who was likely to derive benefit from immunotherapy as opposed to chemotherapy, says Heymach.

John V. Heymach, MD, PhD

Articles

Dr. Heymach on the Efficacy of Mobocertinib in EGFR Exon 20 Insertion–Mutated NSCLC

Dr. Heymach on the Potential Utility of Afatinib in NRG1 Fusion+ NSCLC

Dr. Heymach on the Significance of Nivolumab for Lung Cancer

Dr. Heymach on Nivolumab for Lung Cancer

Dr. Heymach Discusses the CheckMate-026 Study in Lung Cancer