ORLANDO – A large proportion of patients with advanced non–small cell lung cancer (NSCLC) are not being tested for tumor associated–epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) alterations according to national guidelines. This situation may be leading to suboptimal treatment, a large retrospective cohort study suggests.
Guidelines from the American Society of Clinical Oncology and the National Comprehensive Cancer Network recommend testing before first-line therapy for all treatment-eligible patients with nonsquamous histology and for those patients with squamous histology who are nonsmokers or who have mixed cell types or small tumor samples. Additionally, the guidelines recommend that results be made available within 2 weeks of the lab’s receipt of the sample so that they can be used to inform treatment decisions.
Mr. Jay Rughani
Overall, 22% of patients with nonsquamous tumors had no evidence of EGFR and ALK testing in their records. The large majority of patients with squamous tumors did not have any evidence of testing either, and it was unclear how well testing corresponded with the criteria.
In roughly a third of cases in which testing was done, the time between diagnosis of advanced disease and availability of test results exceeded 4 weeks. Among patients with positive test results, those whose results came back after the start of first-line therapy, were about half as likely to appropriately receive a therapy that targeted their tumor’s molecular aberration.
“We observed variation in adherence to [the American Society of Clinical Oncology] and [the National Comprehensive Cancer Network] guidelines around biomarker testing in advanced NSCLC, and we saw significant variation in testing in the squamous population and the nonsquamous population across practices,” presenting author Jay Rughani, manager of Life Sciences at Flatiron Health, New York, commented in an interview. Observed delays in availability of test results were mainly driven by delays between diagnosis and submission of samples to the lab for testing.
“There may be an opportunity to educate the oncology community around testing, certainly for all nonsquamous patients, because this is a case where they all should have been tested,” he said. “And there is also an opportunity to ensure testing of the appropriate squamous cell patients, while discouraging the testing of the majority who aren’t candidates, so there may be an opportunity for education around smoking status.”
Slow uptake of the national guidelines is unlikely to explain the observed variations in testing, according to Mr. Rughani. “Since we looked at patients diagnosed after Jan. 1, 2014, our impression was that the guidelines were sort of disseminated enough and widely known enough by that point, particularly around EGFR and ALK, that we wouldn’t expect any lag there. If we had done this for PD-L1 [programmed death ligand 1] testing, perhaps we might have thought about some lag in adoption.”
The impact of variations in testing and receipt of inappropriate initial therapy on clinical outcomes is yet to be determined. “As a follow-on, some of the work we have been doing is trying to understand, for these separate cohorts of patients, depending on what they received in the front line, what their overall survival was and what their surrogate endpoints were,” Mr. Rughani concluded.
Study details
For the study, the investigators identified 16,316 patients with advanced NSCLC from 206 community clinics across the United States participating in the Flatiron Network. All patients were treated between 2014 and 2016.
Cross-checking of the total Flatiron population against the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results databases suggested that it is a good national representation, according to Mr. Rughani.
A record review showed that the rate of EGFR and ALK testing among study patients ranged widely across clinics, from 0% to 100% for both the nonsquamous cases and the squamous cases, according to results reported in a poster session. The median was 79% for the former and 16% for the latter.
Overall, 22% of the nonsquamous cohort and 79% of the squamous cohort did not have any evidence of testing in their records. For the latter, a sampling of records was unable to verify whether testing was appropriately matched to eligibility criteria.
When testing was performed, 35% of EGFR test results and 37% of ALK test results were not available to the treating clinician until more than 4 weeks after the date of the advanced cancer diagnosis.
“The delays were mostly attributed to nonlab factors. When we isolated the time that the lab took to turn it around, it was under 2 weeks for the vast majority of patients,” Mr. Rughani reported. Possible nonlab culprit factors include clinic work flows, insurance-related issues, and families’ and patients’ hesitancy to be tested, he said.
Delays in receipt of positive test results appeared to influence choice of first-line therapy. Among patients in whom these results were available before first-line therapy, 80% of those found to have an EGFR-mutated tumor received an EGFR–tyrosine kinase inhibitor, and 77% of those found to have ALK-rearranged tumors received an ALK inhibitor.
In sharp contrast, among patients in whom positive test results did not become available until after the start of first-line therapy, respective values were just 43% and 42%.
“Anecdotally, we saw that some patients would go on to Avastin [bevacizumab] in the front line when the results were delayed, and then, ultimately, they would have the opportunity to receive an EGFR[–tyrosine kinase inhibitor] or something like that in later lines,” commented Mr. Rughani. “So, that impacted treatment decisions there.”
Mr. Rughani disclosed stock and other ownership interests in Flatiron Health.