The results have important implications for managed care. Many patients in the study who today would receive surgery and chemotherapy would see a recurrence. In addition, the ability to treat these patients more effectively at earlier stages raises new questions about the need to conduct more lung cancer screening.
Osimertinib, already the first choice to treat patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC), should become the treatment of choice for patients with this mutation who are treated after surgery for early-stage, localized disease, according to investigators who presented results at the American Society of Clinical Oncology (ASCO) annual meeting.
An astonishing 90% of the patients with stage II or stage IIIA NSCLC who received the targeted therapy osimertinib after surgery were alive after 2 years without cancer recurring, compared with 44% of those patients who received placebo, according to data released Thursday by ASCO and presented during Sunday’s plenary session. In patients at these stages, the risk of death or recurrence was reduced by 83%. Median disease-free survival (DFS) for osimertinib = not reached (NR) vs placebo, 20.4 months (HR 0.17; 95% CI: [0.12-0.23], P < .0001).
The full study, called ADAURA, was unblinded early last month after the overwhelming efficacy became evident. AstraZeneca, maker of osimertinib (Tagrisso), a third-generation EGFR tyrosine kinase inhibitor, sponsored the study.
Roy S. Herbst, MD, PhD, the lead study author and chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital, called the trial a “home run” and said the results clearly pointed to giving osimertinib to patients earlier in course of treatment.
“Collectively, these data support the use of osimertinib as an appropriate treatment in the long-term adjuvant setting,” Herbst said, with safety and tolerability being important considerations. “Looking ahead, future considerations for ADAURA include investigation of local versus distant recurrence, sites of disease recurrence, including incidence of [central nervous system] metastases, subsequent therapy, and quality of life.”
Among the overall study population, which covered 682 patients from stage IB to IIIA, treatment with osimertinib reduced the risk of death or recurrence by 79% compared with placebo. Overall, disease-free survival at the 2-year mark was 89% with osimertinib, compared with 53% for placebo.
Of note, Herbst pointed to data that showed patients who had adjuvant chemotherapy fared about the same as those who did not. Among patients who received chemotherapy, the median DFS for osimertinib was NR, compared with 22.1 months for those on placebo (HR 0.18, 95% CI: 0.11-0.29). Among those without chemotherapy, median DFS for osimertinib was NR, compared with 33.1 months for placebo (HR 0.23, 95% CI: 0.13-0.38).
Data for overall survival (OS) are not yet mature, and both Herbst and a discussant acknowledged this might be challenging to evaluate going forward, now that the trial has been unblinded.
Other questions remain, including what happens after 3 years, when patients would be scheduled to stop taking the daily 80 mg tablets? Still, discussant David Spigel, MD, chief scientific officer of the Sarah Cannon Research Institute, said if asked the question he hears in the clinic—which treatment would he give his family—he would choose osimertinib.
The results have important implications for managed care. Today, patients with stage IB to stage III NSCLC who have surgery to remove the tumor typically have chemotherapy, but rates of recurrence are high; Herbst said cancer returns in about half of patients with stage IB disease, and rates are higher at later stages.
In addition, the ability to more effectively treat patients with early stage EGFR-mutated NSCLC tumors raises new questions about the need to screen more patients for lung cancer—and catch more cancers at earlier stages.
Spigel said it unclear at this point whether osimertinib is eliminating disease or “simply controlling and deferring disease that cannot be eradicated.” But the safety and tolerability of the targeted therapy are important, given a planned 3-year treatment course. And, he said, the results were consistent across subgroups.
Adrian Kilcoyne, MD, MBA, MPH, vice president for US Medical Affairs and Health Economics Outcomes Research in Oncology, for AstraZeneca, said the results should be paradigm shifting.
“What we’ve been able to demonstrate is compelling,” Kilcoyne said. Any time a study is stopped early the results are important, but ADAURA “is important in a number of ways.”
“One, it’s telling us that if you hit it early, you can have very compelling results in lung cancer,” Kilcoyne said. “Second, in some of these patients, while they all had surgery, not all of them had adjuvant chemotherapy—half didn’t—and regardless of that you’re seeing a significant benefit.”
“It may drive people to want to identify disease earlier, which is really important, too.”
When asked by The American Journal of Managed Care® if the results might reopen discussion about current US Preventive Services Task Force guidelines on who should be screened for lung cancer, Kilcoyne said, “You’ve asked the million dollar question.”
Current guidelines are based on mix of factors that include a person’s age, smoking history, and how long ago a person quit smoking. Some studies suggest the guidelines do not cast a wide enough net, but a CDC study found earlier this year that even under the current standards, very few eligible for screening are tested.
“We're at a point where we just can't just focus on smoking,” Kilcoyne said. “I think it's where we were going to be, but I think we should look at screening in a far more broad way. It's not just screening patients who would have been smoking, how many pack years, age, etc. … How we screen is going to be incredibly important. We need to embrace newer technology,” that takes a personalized medicine approach.
Herbst RS, Tsuboi M, John T, et al. Osimertinib as adjuvant therapy in patients (pts) with stage IB—IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA. Presented at: The American Society of Clinical Oncology 2020 Annual Meeting. Alexandria, VA: May 28, 2020. Abstract LBA5.