Vassiliki Papadimitrakopoulou, MD, professor, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, discusses biomarker-driven clinical trials in non—small cell lung cancer (NSCLC).

For thoracic oncologists to do better with immunotherapy, they need to better select patients for clinical trials, Papadimitrakopoulou says. More emphasis is also needed on biomarker work in clinical trials because there is concrete evidence that this ultimately leads to improved outcomes. In the KEYNOTE-024 and CheckMate-227 studies, PD-L1 expression and tumor mutation burden, respectively, emerged as biomarkers for immune response. Additional biomarkers predictive of response to single agents and combination therapies would be useful.

Another strategy to consider are neoadjuvant clinical trials that are able to provide enough materials at surgical resection for researchers to identify the mechanism of the drug. Umbrella clinical trials—where patients are allocated into groups based on the therapy they are most likely to derive benefit from&mdash;are also a good strategy, Papadimitrakopoulou says.

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Vassiliki Papadimitrakopoulou, MD, professor, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, discusses biomarker-driven clinical trials in non–small cell lung cancer.

Dr. Papadimitrakopoulou on Biomarker-Driven Clinical Trials in NSCLC

Vassiliki Papadimitrakopoulou, MD, professor, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, discusses impactful targeted therapies in lung cancer.

The most successful targeted therapies are being used in 

mutated disease, Papadimitrakopoulou says. One of the most notable targeted therapies for the treatment of these patients is osimertinib (Tagrisso). Osimertinib is a more selective inhibitor that is better tolerated, and targets central nervous system disease effectively.

Excellent activity has been observed with targeted therapies in

 fusions as well, Papadimitrakopoulou says. Recently, more selective inhibitors of 

 fusions and mutations have also emerged.

Among these advances, there are still challenges. Papadimitrakopoulou says targeting 

mutations has been unsuccessful so far. This alteration will be the subject of clinical trials in an effort to find the mechanisms that make this tumor so invulnerable to current therapies.

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Vassiliki Papadimitrakopoulou, MD, professor, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, discusses impactful targeted therapies in lung cancer.
 

Dr. Papadimitrakopoulou on Impactful Targeted Therapies in Lung Cancer

Vassiliki Papadimitrakopoulou, MD, professor, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, discusses the need for more targeted therapies in non—small cell lung cancer (NSCLC).

The treatment landscape for patients with NSCLC has become very complex, Papadimitrakopoulou says. The most important thing for thoracic oncologists is to develop new therapies that match the patient’s tumor. Physicians have had some success with certain genotypes, particularly with 

 mutations, but there’s still a long way to go with other mutations. About 50% of patients with NSCLC don’t have driver mutations. Within the other 50% of patients, there are still a number of mutations that are not yet targetable, like 

She adds that while immunotherapy has greatly improved outcomes for these patients, there still isn’t a good enough biomarker predictive of response to these treatment options.

Vassiliki Papadimitrakopoulou, MD, professor, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, discusses the need for more targeted therapies in non–small cell lung cancer.

Dr. Papadimitrakopoulou on Importance of More Targeted Therapies in NSCLC

Vassiliki Papadimitrakopoulou, MD, Professor, Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, provides an update on research into pembrolizumab (Keytruda) for the treatment of lung cancer.

Pembrolizumab is currently being studied in patients whose tumors express PD-L1. This is a smart enrichment strategy for treating patients, Papadimitrakopoulou says, and the activity seen so far could be because of this selection. However, all evidence so far points to good activity with this agent in all settings of non-small cell lung cancer.

Vassiliki Papadimitrakopoulou, MD, provides an update on research into pembrolizumab (Keytruda) for the treatment of lung cancer.

Dr. Papadimitrakopoulou Provides an Update on Pembrolizumab for Lung Cancer

Vassiliki Papadimitrakopoulou, MD Professor, Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, discusses the Lung-MAP trial that is exploring MEDI4736, GDC-0032, palbociclib, AZD4547, and rilotumumab in select patients with squamous cell carcinoma of the lung.

In the trial, next-generation sequencing is used to interrogate each tumor sample for multiple alterations, rather than single mutational analysis. The study is then designed to stratify patients to various arms of the program based on each unique molecular subset, giving each patient an opportunity to participate in a clinical trial targeting their exact driver alteration, Papadimitrakopoulou says. If a patient is screened and does not have an alteration, they will be placed in the immunotherapy arm looking at MEDI4736.

The trial features an integrative design that allows patients to transition from the phase II trial to a phase III trial. This provides a more efficient way to get drugs to patients safely and effectively, Papadimitrakopoulou says. The study hopes to speed the discovery of new agents with effective biomarkers for patient with lung cancer. The design of this trial benefits the patients, the academic community and the industry, Papadimitrakopoulou says.

View more from the 15th Annual International Lung Cancer Congress

Vassiliki Papadimitrakopoulou, MD, Professor, Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, discusses the Lung-MAP trial, which uses next-generation sequencing as a screening test rather than screening for one mutation.

Vassiliki Papadimitrakopoulou, MD

Articles

Dr. Papadimitrakopoulou on Biomarker-Driven Clinical Trials in NSCLC

Dr. Papadimitrakopoulou on Impactful Targeted Therapies in Lung Cancer

Dr. Papadimitrakopoulou on Importance of More Targeted Therapies in NSCLC

Dr. Papadimitrakopoulou Provides an Update on Pembrolizumab for Lung Cancer

Dr. Papadimitrakopoulou Discusses the Lung-MAP Trial