Nav: Home

ASCO 2019: 40-50 percent response rate for brigatinib after other next-gen ALK inhibitors

May 30, 2019

Crizotinib was the first drug licensed to treat ALK-positive non-small cell lung cancer (ALK+ NSCLC). Since then, a range of next-generation ALK-inhibitors including ceritinib, alectinib, and brigatinib have earned FDA approval as second-line therapies after treatment with crizotinib. However, each of these next-generation ALK-inhibitors can also be used in the first-line setting, and an important question becomes which, if any, remain useful when given after another next-generation drug? A study by the Academic Thoracic Oncology Medical Investigators' Consortium (ATOMIC) presented at the American Society for Clinical Oncology (ASCO) Annual Meeting 2019 shows 40 percent response rate in 20 patients treated with brigatnib after first-line treatment with another next-gen ALK inhibitor (ASCO abstract 9027). A French retrospective study of 104 patients also presented at ASCO similarly demonstrated a 50 percent response rate in patients treated with brigatinib after two previous lines of ALK inhibitor therapy.

"Brigatinib is already approved for use post-crizotinib and has already shown positive data versus crizotinib in the first-line setting. Meanwhile, the world has moved around us and now we need to know the activity of this drug after a next generation ALK inhibitor," says study first author, Tom Stinchcombe, MD, of Duke Cancer Center. Study colleagues include senior author, and co-principal investigator D. Ross Camidge, MD, PhD, Joyce Zeff Chair in Lung Cancer Research at University of Colorado Cancer Center and Robert C. Doebele, MD, PhD, director of the CU Cancer Center Thoracic Oncology Research Initiative, who is performing key biomarker analyses in the ATOMIC trial.

"A single, small study had previously suggested brigatinib was not likely to be effective in this setting, presumably because not everyone responds the same way to these agents," says Doebele. "So it is very encouraging to see our own data and that of the French group paint a more encouraging picture, worthy of continued exploration."

In addition to measuring overall response rate, the study will perform detailed molecular analyses to help determine the characteristics of patients sensitive to this drug. The study was also able to capture whether patients had progressed in the body or in the brain during treatment with the first-line next-gen ALK inhibitor, allowing investigators to better understand whether brigatinib may be more useful with patients progressing in one or the other site.

"With lung cancer, people progress in different ways - sometimes in the brain, other times in the body. If a drug has greater or lesser activity in the brain than in the body, the efficacy you quote a patient may need to be different depending on their site of progression. Only by pulling these two things apart can you actually guide someone accurately as to their chance of responding to a drug," says Camidge, who recently helped to define the Response Assessment in Neuro-Oncology guidelines, which argue for measuring a drug's effectiveness separately in the body and the brain during cancer clinical trials.

The current trial also demonstrates the ability of the ATOMIC group to successfully utilize a new clinical trial collaboration framework that occupies a middle-ground between industry-sponsored and cooperative group clinical trials.

"The middle ground used to be single center investigator-initiated trials, which allowed doctors and researchers to test their clinical research ideas fairly quickly and cheaply. But, particularly in lung cancer, with the disease fragmenting into many small disease subtypes defined by their genetic make-up, you can't do many investigator-initiated trials at just one site anymore - you'd never get enough patients. Instead, you need multiple investigators collaborating across multiple sites, supported by their own clinical research organization and that's what we've got with ATOMIC," said Camidge, who directs the consortium.
-end-
Enrollment into the ATOMIC brigatinib study continues (NCT02706626).

University of Colorado Anschutz Medical Campus

Related Lung Cancer Articles:

AI helps to fight against lung cancer
Lung cancer has been the leading cause of cancer-related deaths in 2015 in United States.
Free lung-cancer screening in the Augusta area finds more than double the cancer rate of previous screenings
The first year of free lung cancer screening in the Augusta, Ga., area found more than double the rate seen in a previous large, national study as well as a Massachusetts-based screening for this No.
Antioxidants and lung cancer risk
An epidemiological study published in Frontiers in Oncology suggests that a diet high in carotenoids and vitamin C may protect against lung cancer.
Lung cancer may go undetected in kidney cancer patients
Could lung cancer be hiding in kidney cancer patients? Researchers with the Harold C.
Hitgen and Cancer Research UK's Manchester Institute enter license agreement in lung cancer
Cancer Research UK, Cancer Research Technology (CRT), the charity's commercial arm, and HitGen Ltd, a privately held biotech company focused on early drug discovery, announced today that they have entered into a licence agreement to develop a novel class of drugs against lung cancer.
Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Huntsman Cancer Institute research holds promise for personalized lung cancer treatments
New research from scientists at Huntsman Cancer Institute (HCI) at the University of Utah uncovered distinct types of tumors within small cell lung cancer that look and act differently from one another.
High levels of estrogen in lung tissue related to lung cancer in postmenopausal women
Researchers from Kumamoto University, Japan have found that postmenopausal women with multicentric adenocarcinoma of the lung have a higher concentration of estrogen in non-cancerous areas of the peripheral lung than similar women diagnosed with single tumor lung cancer.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Pericardial window operation less efficient in cases of lung cancer than any other cancer
Pericardial window operation, a procedure, where abnormal quantity of malignant fluid, surrounding the heart, is drained into the neighbouring chest cavity, is commonly applied to patients diagnosed with cancer.

Related Lung Cancer Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...