Geoffrey R. Oxnard, MD, associate professor of medicine, Harvard Medical School, thoracic oncologist, Dana-Farber Cancer Institute, discusses 

 fusions in patients with non—small cell lung cancer (NSCLC).

 fusions are very rare in NSCLC, but they are seen as frequently as 

 fusions, which have become its own established subset of lung cancer. 

 mutations. Oxnard says that researchers know these mutations can be very targetable despite their uniqueness. About 1% to 2% of patients with NSCLC will present with 

 fusions. It is more common to see this in adenocarcinomas or patients who are never- or light-smokers.

 fusions are still seen on standard next-generation sequencing panels. Just like 

, Oxnard says it’s important for researchers to understand that 

 can be targeted. It’s worth noting that the current liquid biopsy technology is not sophisticated enough to pick up most types of fusions. If a liquid biopsy turns up negative, another analysis of the tumor should be done to get definitive results.

Videos

Geoffrey R. Oxnard, MD, associate professor of medicine, Harvard Medical School, thoracic oncologist, Dana-Farber Cancer Institute, discusses RET fusions in non–small cell lung cancer.

Dr. Oxnard Discusses RET Fusions in NSCLC

Geoffrey R. Oxnard, MD, associate professor of medicine, Harvard Medical School, thoracic oncologist, medical oncology, Dana-Farber Cancer Institute, discusses the potential impact of implementing cell-free DNA (cfDNA) tests as a method to detect signs of early stage cancer.

Initial results from the Circulating Cell-free Genome Atlas Study in patients with early stage lung cancer strongly suggest that cfDNA tests can be used with a high degree of specificity to detect signs of disease. There were 3 prototype sequencing assays that were used—paired cfDNA and white blood cell-targeted sequencing for single nucleotide variants/indels, paired cfDNA and WBC whole genome sequencing for copy number variation, and cfDNA whole genome bisulfite sequencing for methylation.

Oxnard says that this approach to a cancer detection test is different than what is being done in the clinic currently. If this assay was done with the next-generation sequencing panels that are done today, then there would be a problem with false positives. Oxnard says that the tools available right now cannot be used to detect cancer, and they need to be redeveloped for this specific purpose.

Geoffrey R. Oxnard, MD, associate professor of medicine, Harvard Medical School, thoracic oncologist, medical oncology, Dana-Farber Cancer Institute, discusses the potential impact of implementing cell-free DNA tests as a method to detect signs of early stage cancer.
 

Dr. Oxnard on Potential of Genome Wide Sequencing With cfDNA

Geoffrey R. Oxnard, MD, associate professor of medicine, Harvard Medical School, thoracic oncologist, medical oncology, Dana-Farber Cancer Institute, discusses the design and importance of the Circulating Cell-free Genome Atlas Study study in an interview with 

Initial data from this study suggest that cell-free DNA assays can be used with a high degree of specificity to detect signs of early stage lung cancer.

Moreover, the study included 3 types of prototype sequencing assays. These included paired cfDNA and white blood cell targeted sequencing for single nucleotide variants/indels, paired cfDNA and WBC whole genome sequencing for copy number variation, and cfDNA whole genome bisulfite sequencing for methylation.

Geoffrey R. Oxnard, MD, associate professor of medicine, Harvard Medical School, thoracic oncologist, medical oncology, Dana-Farber Cancer Institute, discusses the design and importance of the Circulating Cancer Genome Atlas (CCGA) study in an interview with OncLive during the 2018 ASCO Annual Meeting.

Dr. Oxnard Discusses the Circulating Cell-Free Genome Atlas Study

Geoffrey R. Oxnard, MD, physician, assistant professor of medicine, Harvard Medical School, Dana-Farber Cancer Institute, discusses the role of osimertinib (Tagrisso) in the TATTON trial for patients with lung cancer.

The TATTON trial investigated osimertinib plus different combination therapies of durvalumab (Imfinzi), selumetinib, and savolitinib, states Oxnard.

Osimertinib with durvalumab was shown to be toxic, while osimertinib with selumetinib was found to be tolerable. Osimertinib and savolitinib is the combination that is moving forward to phase II development, explains Oxnard.

Dr. Oxnard on the Role of Osimertinib in the TATTON Trial for Lung Cancer

Geoffrey R. Oxnard, MD, physician, assistant professor of medicine, Harvard Medical School, Dana-Farber Cancer Institute, discusses resistance mechanisms that occur in patients with 

-positive T790M non—small cell lung cancer (NSCLC) following treatment with osimertinib (Tagrisso).

Oxnard and colleagues are currently investigating the question of, "what happens after patients develop resistance to osimertinib? What is the next treatment approach?" In patients undergoing a biopsy for resistance to osimertinib, practitioners look for 2 types of resistance, Oxnard explains. For example, there are patients who develop resistance later on treatment with osimertinib, maintain T790M on resistance, and acquire new 

However, in patients who experience early resistance to osimertinib, T790M is suppressed and other competing mechanisms overgrow T790M, such as small cell transformation and 

 amplification. These are poor prognosis factors, and researchers must identify targeted therapies to target these newer mechanisms of resistance. For example, the TATTON trial is investigating osimertinib combined with a MET inhibitor to suppress these competing clones, he adds.

Geoffrey R. Oxnard, MD, physician, assistant professor of medicine, Harvard Medical School, Dana-Farber Cancer Institute, discusses resistance mechanisms that occur in patients with EGFR-positive T790M non

Dr. Oxnard on Detecting Resistance Mechanisms After Treatment With Osimertinib

Geoffrey R. Oxnard, MD, Assistant Professor of Medicine, Harvard Medical School, Dana Farber Cancer Institute, discusses how to define resistance to EGFR-inhibitors in lung cancer.

A lot of lung cancer patients that are identified as having acquired resistance to an EGFR-inhibitor are asymptomatic, says Oxnard. While it may be determined that a patient has progressed based lesion growth by a radiation oncologist, it is possible that a patient may be able to stay on their first-line treatment after this growth and still see benefit.

Waiting a couple more months before starting second-line therapy can allow patients to delay the toxicities that come with chemotherapy, and allow the oncologist to determine the best action plan for their treatment, says Oxnard.

View more from the 2015 NY Lung Cancer Symposium

Geoffrey R. Oxnard, MD

Articles

Dr. Oxnard Discusses RET Fusions in NSCLC

Dr. Oxnard on Potential of Genome Wide Sequencing With cfDNA

Dr. Oxnard Discusses the Circulating Cell-Free Genome Atlas Study

Dr. Oxnard on the Role of Osimertinib in the TATTON Trial for Lung Cancer

Dr. Oxnard on Detecting Resistance Mechanisms After Treatment With Osimertinib

Dr. Oxnard on Delaying Second-Line Treatment in EGFR-Mutant Lung Cancer