Summary
Data from a phase III study demonstrated that treatment with osimertinib following surgery for localized non-small cell lung cancer (NSCLC) with an EGFR mutation significantly improved disease-free survival (DFS). The findings were presented at the ASCO 2020 Annual Meeting (Abstract LBA5).
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Original Article
Adjuvant Osimertinib Delays Recurrence in Localized NSCLC
Oncology Times
By Catlin Nalley
Data from a phase III study demonstrated that treatment with osimertinib following surgery for localized non-small cell lung cancer (NSCLC) with an EGFR mutation significantly improved disease-free survival (DFS). The findings were presented at the ASCO 2020 Annual Meeting (Abstract LBA5).
The researchers reported that 90 percent of patients with stage II-IIIA NSCLC who received osimertinib, were alive at 2 years without disease recurrence versus 44 percent of those who received a placebo. The risk of recurrence or death was reduced by 83 percent for stage II-IIIA patients treated with osimertinib after surgery compared to placebo.
“Lung cancer is the leading cause of cancer death worldwide with more than 1.7 million deaths annually,” noted lead author Roy S. Herbst, MD, PhD, who is the Chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital, and the Associate Cancer Center Director for Translational Research at Yale Cancer Center. “[This is] more than breast, prostate, and colorectal cancers combined. Non-small cell lung cancer represents 85 percent of these lung cancer cases with an estimated 30 percent of these patients presenting with resectable disease at diagnosis.
“Even though these tumors are resected, patients will still recur,” he explained, during a press briefing. “We have adjuvant chemotherapy that has been well-defined with drugs such as cisplatin, [which are] are used in these settings. However, the 5-year overall survival benefit with this therapy is only about 5 percent. And of course, there are toxicities. Overall rates of disease recurrence following surgery and adjuvant therapy remain high.”
Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, has had significant results in the metastatic setting as a frontline agent, according to Herbst. It is approved in the U.S. for first-line treatment of patients with metastatic, EGFR mutation positive NSCLC.
“So, now what we're doing in this trial is taking [osimertinib] from the frontline metastatic setting, and we're moving it earlier in patient's disease in hopes of an even better benefit,” he noted.
Study Details
In the multi-national, randomized, controlled phase III ADAURA trial, 682 patients with primary non-squamous stage IB-IIIA NSCLC and confirmed EGFR mutation were randomized to receive adjuvant osimertinib (n=339) or placebo (n=343).
Eligible patients included those that had a full recovery from complete resection of primary NSCLC. Postoperative chemotherapy was allowed. Those who received osimertinib took 80 mg tablets once daily for up to 3 years.
Baseline characteristics were balanced across arms, according to the study authors. In both arms, 31 percent of patients had stage IB disease and 69 percent were stage II/IIIA. The majority of patients in both groups were female—68 percent in the osimertinib group and 72 percent in the placebo cohort.
The primary endpoint was DFS in stage II-IIIA patients. The secondary objectives include DFS in the overall population; DFS at 2,3,4, and 5 years; as well as OS, safety, and quality of life.
Results from this trial were so compelling that the independent data monitoring committee recommended early unblinding. Among patients with stage II-IIIA disease, there was an 83 percent reduction in the risk of disease recurrence or death, according to Herbst.
“These are extraordinary results,” he noted. “This was much better than expected and certainly is something that's going to help patients.”
In the overall population (stage IB-IIIA), adjuvant osimertinib reduced the risk of disease recurrence or death by 79 percent compared to placebo. Additionally, DFS at 2 years was 89 percent with osimertinib versus 53 percent in the placebo group. At the time of data analysis, overall survival was immature.
“The next question is: was the drug tolerated? The answer is yes. The median duration of exposure for osimertinib was 22.3 months and 18.4 months for placebo,” Herbst noted, reporting that osimertinib was well-tolerated and consistent with its known safety profile. No AEs led to death in the osimertinib arm and the rate of grade 3 or higher AEs was low.
Conclusions & Implications
These findings demonstrate the efficacy of osimertinib and establishes it has an alternative option for localized NSCLC with EGFR mutation. “Adjuvant osimertinib is the first targeted agent in a global randomized trial to show statistically significant and clinically meaningful improvement in DFS in patients with stage IB-IIIA, EGFR-mutation positive NSCLC,” said Herbst.
“Osimertinib is already the frontline standard of care for patients with EGFR-mutated advanced non-small cell lung cancer. The improvement in disease-free survival seen in this study strongly supports the use of this targeted therapy in earlier stage disease, which has a significant risk of recurrence despite surgical treatment and chemotherapy,” commented ASCO Chief Medical Officer and Executive Vice President Richard L. Schilsky, MD, FACP, FSCT, FASCO, in a statement.
“Adjuvant osimertinib provides a highly effective, practice-changing treatment for [these] patients after complete tumor resection,” Herbst concluded, recalling what his mentor, Isaiah ‘Josh’ Fidler, PhD, from MD Anderson, taught him. “He taught all of us that it’s metastases. It's the spread of tumor that kills patients. And drugs such as this, based on biology and given to patients at the earliest possible time, prevent those metastases and allow patients to live longer with better quality of life.”
Catlin Nalley is a contributing writer.