As of April 20, 2018
Study of 2 groups of patients. Group A = 129 patients, Group B = 577 patients.
The most frequent variants were Variant 1 (43%) and Variant 3 (40%).
“ALK resistance mutations were significantly more common in variant 3 than in variant 1 (57% v 30%).”
“In particular, ALK 1202R was more common in variant 3 than in variant 1 (32% v 0%).”
“Among patients treated with the third-generation ALK TKI lorlatinib, variant 3 was associated with a significantly longer progression-free survival than variant 1.”
As of February 12, 2018
Pfizer filed a new drug application (NDA) for lorlatinib with the FDA, Japan, and Europe for use in patients with ALK-positive lung cancer. FDA’s decision is expected by the end of August.
In support of the 3 applications, Pfizer submitted data from the phase II part of a phase I/II trial in which the overall response rate (ORR) was 69% in ALK-positive patients previously treated with crizotinib (Xalkori) with or without chemotherapy, and the Intracranial ORR was 68%. See previous posts for more detail.
As of January 23, 2018 and March 29, 2018:
Plasma genotyping by Next Generation Sequencing (Liquid Biopsy) can be used to track evolution of resistance to various ALK inhibitors.
On April 28, 2017 the FDA granted Takeda (formerly Ariad) approval for Alunbrig (brigatinib) to be sold in the US to patients who are resistant to Crizotinib.