ASCO: Entrectinib gets edge over crizotinib against ROS1+ lung cancer

May 30, 2019

Crizotinib and entrectinib are both active against ROS1+ non-small cell lung cancer. But which is best? The answer seems easy: Just compare the drugs' clinical trial results. However, not all trials are created equal, and these differences in trial designs can lead to irrelevant comparisons - like comparing athletes' running times without noting that one ran a kilometer while the other ran a mile. Now results from an innovative, "virtual" clinical trial presented at the American Society for Clinical Oncology (ASCO) Annual Meeting 2019 attempt to place crizotinib and entrectinib on an equal playing field. In this analysis, patients taking entrectinib were able to stay on treatment longer and had about almost 6 months longer progression-free survival than patients treated with crizotinib.

"ROS1 alterations are pretty rare. When asked why not just do a randomized clinical trial of entrectinib vs. crizotinib, we responded that we would not have those results for many years - and it would likely be an underpowered study, meaning we might not even get an adequate answer! We didn't think that made sense. While we were doing that, patients with lung cancer, and especially lung cancer patients whose disease had spread to the brain, wouldn't be getting adequate therapy," says Robert C. Doebele, MD, PhD, director of the University of Colorado Cancer Center Thoracic Oncology Research Initiative, and the study's first author.

Instead, Doebele and colleagues (including from entrectinib manufacturer, Roche), decided to take a different approach. Combing through tens of thousands of de-identified electronic patient records from Flatiron Health, the authors found 69 patients treated with crizotinib who matched the enrollment requirements for 53 patients on trials of entrectinib. Finally, they were able to compare apples with apples - a single population treated with one or the other drug.

"The purpose of this trial was to go to this real-world data aggregator, Flatiron Health, to recreate the data of a crizotinib trial so that patients were more like those on entrectinib trials. Although it is challenging to do this from extracted chart data, we tried really hard to select patients who looked similar to those in the entrectinib clinical trial, for example by making sure that a comparable number of patients in the crizotinib arm had brain metastases," Doebele says.

One measure of a drug's effectiveness is how long a patient stays on the drug (because when a drug stops working, patients move on to other treatments). The median time to treatment discontinuation (TTD) of patients in this real-world crizotinib cohort was 8.8 months; the TTD of patients using entrectinib was 14.6 months. Compared with patients on entrectinib, patients on crizotinib had an additional 44 percent chance that their cancer would resume its growth.

"It was an attempt to perform a virtual clinical trial," Doebele says. "There may be a lot of limitations of this type of approach, but we think it's a novel way to use all of this big data that people are generating to learn important things about cancer treatment and speed the use of new drugs to patients who need them."
-end-


University of Colorado Anschutz Medical Campus

Related Lung Cancer Articles from Brightsurf:

State-level lung cancer screening rates not aligned with lung cancer burden in the US
A new study reports that state-level lung cancer screening rates were not aligned with lung cancer burden.

The lung microbiome may affect lung cancer pathogenesis and prognosis
Enrichment of the lungs with oral commensal microbes was associated with advanced stage disease, worse prognosis, and tumor progression in patients with lung cancer, according to results from a study published in Cancer Discovery, a journal of the American Association for Cancer Research.

New analysis finds lung cancer screening reduces rates of lung cancer-specific death
Low-dose CT screening methods may prevent one death per 250 at-risk adults screened, according to a meta-analysis of eight randomized controlled clinical trials of lung cancer screening.

'Social smokers' face disproportionate risk of death from lung disease and lung cancer
'Social smokers' are more than twice as likely to die of lung disease and more than eight times as likely to die of lung cancer than non-smokers, according to research presented at the European Respiratory Society International Congress.

Lung cancer therapy may improve outcomes of metastatic brain cancer
A medication commonly used to treat non-small cell lung cancer that has spread, or metastasized, may have benefits for patients with metastatic brain cancers, suggests a new review and analysis led by researchers at St.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Lung transplant patients face elevated lung cancer risk
In an American Journal of Transplantation study, lung cancer risk was increased after lung transplantation, especially in the native (non-transplanted) lung of single lung transplant recipients.

Proposed cancer treatment may boost lung cancer stem cells, study warns
Epigenetic therapies -- targeting enzymes that alter what genes are turned on or off in a cell -- are of growing interest in the cancer field as a way of making a cancer less aggressive or less malignant.

Are you at risk for lung cancer?
This question isn't only for people who've smoked a lot.

Read More: Lung Cancer News and Lung Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.