Large Survival Edge in Lung Cancer With Companion Diagnostics, but Some Still Miss Out, Study Finds

Patients with lung cancer who received a companion diagnostic as part of their initial treatment had a 3-fold greater survival benefit than those who were not tested—but some patients still don’t get tested.

Authors of findings published this week in The Oncologist, which they report is the largest real-world study of its kind, said it confirms the frustration that surrounds precision medicine in cancer care.

“Despite level 1 evidence supporting the benefits of biomarker-driven therapeutic approaches and consensus among national and international guidelines for the routine use of [companion diagnostic] testing in [advanced non—small cell lung cancer], it is not clear whether this evidence has translated to practice in real world settings,” they wrote.

The results are based on an analysis of data from the Flatiron Health database, using patient records from 2011 to 2018. The authors are from divisions of Roche and from Peter MacCallum Cancer Centre in Australia. Roche funded the study; it acquired Flatiron for $1.9 billion in 2018.

What makes a difference in who gets tested? Authors say the data show women are more likely to be tested than men, smokers are less likely to be tested than non-smokers, and Asians as a group are likely to be tested.

The study found that as of May 31, 2018, only 14,732 patients with nonsquamous non—small cell lung cancer (NSCLC) received a companion diagnostic test out of 33,742 adult patients eligible for testing in the Flatiron Health database. However, the percentage who received testing increased significantly over time: Only 21.7% of eligible patients with nonsquamous NSCLC were tested from 2011-2013, while 62.2% of these patients were tested from 2014 to 2018.

Companion diagnostic (CDx) testing identifies patients most likely to benefit from biomarker-driven treatments. Much of the promise in lung cancer treatment comes from use of testing to match patients with targeted therapies, checkpoint inhibitors, or combinations; this year’s meeting of the American Society of Clinical Oncology featured the CITYSCAPE and ADAURA trials that relied on testing.

Most of the study focused on results for 17,555 patients who met the study’s analysis criteria. These patients had nonsquamous advanced NSCLC and were classified into 1 of 2 groups: those who tested for 1 of 4 driver mutations (ALK, BRAF, EGFR, or ROS1 positive or negative) and/or PD-L1 expression according to the Flatiron data; this was the CDx group, n = 14,732 patients; the second group did not have reported evidence of testing, including those with no CDx test or testing status unknown; this was the no-CDx group, n= 2823 patients.

The researchers found that the patients had a mean age at diagnosis of 67.2 years, and two-thirds were white (67.1%). Most had insurance (91.7%). Among those tested, the median time from diagnosis to the first test was 19.0 days, and the median time from advanced diagnosis to the first line of treatment was 33 days.

There were differences between those tested and those not tested:

• More in the CDx group (49.4%) received >1 line of therapy than in the no-CDx group (24.9%).
• 75.9% in the CDx group had received test results before or at start of treatment
• Regional differences were seen: patients living in the Northeast or West were more likely to get CDx tests than patients in the Midwest, with point estimate 1.30 (95% CI, 1.13-1.50) and 1.34 (95% CI, 1.15-1.57), respectively.
• Smokers were less likely to be tested than non-smokers, with a point estimate of 0.35 (95% CI, 0.29-0.41).
• While there were not many Asian patients in the study (n = 473), they were more likely to be tested than white patients, with a point estimate of 2.55 (95% CI, 1.56-4.18).

Being tested meant living longer: Patients with CDx testing had a longer median survival than those without (95% CI) 13.04 months (12.62-13.40 months) vs 6.01 months (5.72 months-6.24 months). Patients with testing also had decreased mortality risk, with an unadjusted hazard ratio (95% CI) of 0.54 (0.52-57).

When patients had CDx testing and biomarker-driven therapy as their first line of treatment, the results were even more remarkable compared with those who did not have testing: the median survival was 18.00 months (16.66-19.22) vs 6.01 (5.72-6.24 months). Patients who had their first CDx on or prior to the first line of treatment also had a longer median overall survival than those not tested (95% CI): 12.78 vs 6.01 months.

“Since the prognosis for patients with advanced NSCLC is generally very poor, a dire need exists for earlier initiation of care through diagnostic testing and biomarker-driven treatment strategies. Based on this, it is evident that a standard “one size fits all” approach in the treatment of cancer and many other disease areas does not always result in optimal patient outcomes,” the authors concluded.

“Precision medicine, in contrast, is an expanding treatment approach that can help match patients to the most effective treatments sooner based on an individual’s characteristics, including specific molecular targets likely to respond to biomarker-driven therapies.”

Reference

John A, Shan AS, Wong WB, Schneider CE, Alexander M. Value of precision medicine in advanced non-small cell lung cancer: real-world outcomes associated with the use of companion diagnostics. The Oncologist. Published online July 6, 2020. doi:10.1634/theoncologist.2019-0864