GRACE :: Lung Cancer



Denise Brock

ASCO 2017 – Lung Cancer – A Practice Change for ALK+ Lung Cancer Patients, Alecensa for First Line Treatment



H. Jack West, MD 

Medical Director 

Thoracic Oncology Program Swedish Cancer Institute

President & CEO, GRACE 


Matthew Gubens, MD

Thoracic Oncologist

Thoracic Surgery and Oncology Clinic of the UCSF Helen Diller Family Comprehensive Cancer Center

Jyoti D. Patel, MD

Director Thoracic Oncology

University of Chicago Medicine

Drs. H. Jack West, Medical Director of the Thoracic Oncology Program at Swedish Cancer Institute in Seattle, Washington and President and CEO of GRACE, Matthew Gubens, Thoracic Oncologist at the Thoracic Surgery and Oncology Clinic of the UCSF Helen Diller Family Comprehensive Center in San Francisco, California, and Jyoti Patel, Director of Thoracic Oncology at University of Chicago Medicine gathered post meeting to discuss new information from ASCO 2017 regarding lung cancer.   In this roundtable video, the doctors discuss A Practice Change for ALK+ Lung Cancer Patients, Alecensa for First Line Treatment.




 Please feel free to offer comments and raise questions in our Discussion Forums.

GRACE would like to thank the following sponsors for their support of this program



Dr West

New FDA Approval for Zykadia (ceritinib) for ALK-Positive NSCLC: Why I Think It’s a Poor Choice for Initial Treatment


The FDA just approved a new therapy for the approximately 4% of patients with NSCLC who have the molecular marker known as an ALK rearrangement. The agent Zykadia (ceritinib), a “second generation” ALK inhibitor that is more effective than Xalkori (crizotinib) in lab models of ALK-positive NSCLC, and the new approval was for Zykadia as first line treatment for ALK-positive lung cancer, a setting where we have historically favored Xalkori since it was approved in 2011. . Despite the FDA approval for ceritinib, I don’t believe it should be favored as a first line therapy for ALK-positive patients. Why would I not favor it?

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Dr West

Should Alecensa (Alectinib) be the new first line ALK inhibitor for ALK-positive NSCLC?


Probably the most immediate potentially practice-changing presentation from ASCO was the Japanese J-ALEX study in the subset of about 4-5% of patients with non-small cell lung cancer (NSCLC) who have the molecular driver known as an anaplastic lymphoma kinase (ALK) rearrangement, which we now routinely test for from the tumor tissue of patients with a non-squamous metastatic NSCLC.   The current historical standard of care as first line treatment is Xalkori (crizotinib), which is an ALK inhibitor that happened to be readily available when the ALK rearrangement was first being studied in NSCLC about 5-7 years ago. Though it was granted an accelerated FDA approval back in 2011 based on early very promising activity and has since been confirmed to be superior to chemotherapy as first line treatment in ALK-positive patients, it is a less active ALK inhibitor than many other “second-generation” ALK inhibitors such as Zykadia (ceritinib) and Alecensa (alectinib), both now FDA-approved for patients who have developed progression after Xalkori or who are not able to tolerate it, as well as other agents still in development, including brigatinib (likely to become approved soon), and a few others further behind in development but also very active against ALK-positive NSCLC.

A question that logically follows is whether it is better to give one of these more active second generation ALK inhibitors as first line therapy, where they are likely to be more active for longer than if given for “acquired resistance” after Xalkori, or whether it’s better to start with Xalkori and have other powerful ALK inhibitors left for later.  Should we use our best drug up front or only the most effective drug required to do the job for now, saving something in the tank as we think more about advanced lung cancer as a distance race than a sprint? How much do we prioritize control now vs. options later?

There are several trials that have been initiated that all test a second generation ALK inhibitor vs. Xalkori.  Two of the first to be completed compare Alecensa to Xalkori, a large, global trial known as ALEX, and a smaller trial done in Japan only, known as J-ALEX, which reported early and remarkably interesting results at ASCO 2016.

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New Ideas and New Treatment Options for Acquired Resistance for ALK/ROS1




Xalkori (critzotinib) was the first approved treatment for ALK+ and ROS1 lung cancer. Since then, other drugs have been approved or are currently undergoing scientific review. In this video, Dr. Owonikoko outlines these options for patients.

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