Katie Kerrigan, MD, a hematology/oncology fellow at Huntsman Cancer Institute, University of Utah School of Medicine, discusses sequencing challenges in the treatment of patients with 

One of the biggest challenges that needs to be addressed with future research has to do with determining the optimal sequencing of available agents, says Kerrigan. Patients with 

-mutated disease often live a long time, and there are no overall survival data available for the available second- and third-generation ALK TKIs, Kerrigan adds.

Understanding how best to sequence these agents is necessary to provide patients with the maximum benefit for the longest period of time. In the United States, alectinib (Alecensa) has become the frontline standard of care for patients with 

-positive disease, based on findings from the phase III ALEX trial. It is unknown whether another second-generation TKI, brigatinib (Alunbrig), is efficacious post-alectinib, says Kerrigan. In fact, data from some retrospective reviews suggest that the agent may not be too active in these patients, and that lorlatinib (Lorbrena) may be the superior option.

Another unanswered question has to do with the role of immunotherapy in this space, adds Kerrigan. Although available data suggest that single-agent immunotherapy may not be effective in this patient population, researchers postulate that more activity may be observed if the approach is combined with chemotherapy or chemotherapy plus a VEGF inhibitor, concludes Kerrigan.

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Katie Kerrigan, MD, discusses sequencing challenges in the treatment of patients with ALK-positive non–small cell lung cancer.

Dr. Kerrigan on Sequencing Challenges in ALK+ NSCLC

Katie Kerrigan, MD, a hematology/oncology fellow at Huntsman Cancer Institute, University of Utah School of Medicine, discusses remaining challenges in the treatment of patients with 

Patient selection is still lacking in this space, says Kerrigan, who adds that once she knows a patient has 

-mutated disease, she will base her treatment decision on whether or not they have brain metastases. If these metastases are present, she prefers to use entrectinib (Rozlytrek) over crizotinib (Xalkori) in the frontline setting, as entrectinib has been shown to have higher responses in the brain.

The challenge is that entrectinib is still very new, says Kerrigan. The agent received approval in August 2019 for the treatment of adult patients with 

-positive metastatic disease as well as adult and pediatric patients ≥12 years of age with solid tumors that harbor an 

 fusion. More data are needed to determine if entrectinib is superior to crizotinib, Kerrigan adds.

However, repotrectinib (TPX-0005) has also emerged in this space, and data from phase I trials reported at the 2019 ASCO Annual Meeting have shown that treatment with the agent led to an impressive overall response rate of 100% in the brain, says Kerrigan. These early data suggest that repotrectinib is highly efficacious in both the brain and body, says Kerrigan, and as such, phase II and III trials further examining the agent are warranted. 

Katie Kerrigan, MD, discusses remaining challenges in the treatment of patients with ROS1-positive non–small cell lung cancer.

Dr. Kerrigan on Remaining Challenges in ROS1+ NSCLC

Katie Kerrigan, MD, a hematology/oncology fellow at Huntsman Cancer Institute, University of Utah School of Medicine, discusses the design and findings of the ongoing phase I PROFILE 1001 trial with crizotinib (Xalkori) in 

-mutated non—small cell lung cancer (NSCLC).

PROFILE 1001 is the initial phase I study evaluating the use of crizotinib in heavily pretreated patients with 

-mutated advanced NSCLC. Notably, patients with brain metastases were included in the trial, says Kerrigan.

Crizotinib was found to be very effective in those with 

-mutated disease, leading to a median progression-free survival of 19.3 months and a median overall survival of 51.4 months. In 2016, the FDA approved crizotinib for the treatment of patients with 

-positive metastatic NSCLC, which revolutionized the management of this patient population, concludes Kerrigan.

Katie Kerrigan, MD, a hematology/oncology fellow at Huntsman Cancer Institute, University of Utah School of Medicine, discusses the design and findings of the ongoing phase I PROFILE 1001 trial with crizotinib (Xalkori) in ROS1-mutated non–small cell lung cancer (NSCLC).

Katie Kerrigan, MD

Articles

Dr. Kerrigan on Sequencing Challenges in ALK+ NSCLC

Dr. Kerrigan on Remaining Challenges in ROS1+ NSCLC

Dr. Kerrigan on Design and Findings of the PROFILE 1001 Trial in ROS1-Mutated NSCLC