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Osimertinib (Tagrisso) demonstrated promising clinical activity as first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) with uncommon EGFR mutations, the nonrandomized UNICORN trial from Japan showed.

Among 40 patients treated with the third-generation EGFR tyrosine kinase inhibitor (TKI), 55% responded and the disease control rate reached 90%, with a median duration of response of 22.7 months, reported Yusuke Okuma, MD, PhD, of the National Cancer Center Hospital in Tokyo, and colleagues.

At a median follow-up of 12.7 months, the median progression-free survival (PFS) was 9.4 months, median time to treatment failure was 9.5 months, and median overall survival was not reached, they noted in

"This nonrandomized clinical trial met its primary endpoint, with osimertinib showing clinical activity with manageable toxic effects for previously untreated patients with metastatic NSCLC harboring uncommon EGFR mutations other than the exon 20 insertion," the authors concluded. "The results support the use of osimertinib as a treatment option for this patient population."

As explained by Okuma and colleagues, EGFR TKIs are the standard of care for patients with metastatic NSCLC harboring EGFR mutations. However, they noted, uncommon EGFR mutations are rare and represent a range of diverse mutations, and the optimal management of these patients has yet to be determined.

In a , Victoria Wang, MD, PhD, of the University of California San Francisco, and Justin Gainor, MD, of Massachusetts General Hospital in Boston, wrote that the study addressed an important molecular subgroup that has been overlooked in previous clinical trials.

While asserting that UNICORN and previous studies "support consideration of osimertinib as an additional agent within the treatment armamentarium for patients with uncommon EGFR mutations," Wang and Gainor also pointed out that the data show that "one size does not fit all," meaning that clinical outcomes have been heterogeneous among patients with the most common atypical EGFR mutations.

For example, Okuma and colleagues observed that patients with EGFR L861Q mutations had an overall response rate (ORR) of 75%, while those with EGFR G719X and S768I mutations had ORRs of 45% and 50%, respectively. Wang and Gainor noted that the , which enrolled 37 patients with atypical EGFR mutations treated with osimertinib in Korea, demonstrated similar response rates for patients with those mutations.

"[A]typical EGFR mutations represent a diverse and heterogenous group, and treatment of these patients using small molecules must be individualized, accounting for the molecular nature of each mutation and its functional impact on the protein and drug interaction to guide therapy," they wrote.

UNICORN was an open-label, single-group, phase II trial that enrolled 42 patients from 18 hospitals in Japan who had previously untreated metastatic NSCLC harboring uncommon EGFR mutations other than exon 20 insertions.

Of the 40 patients eligible for study, median age was 72, 55% were men, and 92.5% had adenocarcinoma. Seventeen patients had never smoked; 55% had solitary mutations, and 45% had compound mutations, with at least one uncommon EGFR mutation.

All participants received osimertinib 80 mg orally once daily until disease progression or unacceptable toxic effects occurred.

The ORR for patients with solitary or compound uncommon EGFR mutations was 45.5% and 66.7%, respectively, while median PFS was 5.4 months and 9.8 months, and median OS was 23 months and not reached. OS rates at 1 and 2 years were 81.3% and 62.1%, respectively. At data cutoff, 72.5% of patients were alive.

As for safety, Okuma and colleagues reported that all patients had at least one adverse event (AE) of any grade, with 11 experiencing a grade 3 or 4 AE. The most common AEs were hypoalbuminemia (90%), anemia (80%), thrombocytopenia (65%), and elevated creatinine (60%), while the most common nonhematologic toxic effects were diarrhea (47.5%), acneiform eruption (42.5%), and oral mucositis (32.5%). Five patients developed interstitial lung disease.

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