In an interim analysis of a Japanese trial (ACHILLES/TORG1834) reported in the Journal of Clinical Oncology, Miura et al found that afatinib prolonged progression-free survival vs platinum-based chemotherapy in patients who had treatment-naive nonsquamous non–small cell lung cancer (NSCLC) with uncommon activating EGFR mutations.
As stated by the investigators: “To our knowledge, the ACHILLES/TORG1834 trial is the first randomized study comparing afatinib and chemotherapy in patients with…NSCLC harboring sensitizing uncommon…EGFR mutations.”
Study Details
In the investigator-initiated, open-label, multicenter trial, 109 patients with stage III/IV or recurrent disease were randomly assigned 2:1 between March 2019 and February 2023 to receive afatinib at 30 or 40 mg daily (at physician’s discretion, selected prior to random assignment; n = 73) or platinum (cisplatin or carboplatin) and pemetrexed followed by pemetrexed maintenance (n = 36). Uncommon EGFR mutations included exon 20 insertions and T790M mutations. The primary endpoint was progression-free survival.
Key Findings
At interim analysis, the data and safety monitoring committee recommended early study termination.
Median progression-free survival was 10.6 months (range = 8.2–12.8 months) in the afatinib group vs 5.7 months (range = 4.2–7.2 months) in the chemotherapy group (hazard ratio [HR] = 0.421, 95% confidence interval = 0.251–0.706, P = .0010). Hazard ratios vs chemotherapy were 0.128 (P < .0001) among 36 patients receiving afatinib at 40 mg and 0.704 (P = .3197) among 37 patients receiving 30 mg.
Objective response rates were 61.7% in the entire afatinib group, 55.8% among those with major uncommon mutations (G719X, L861Q), 72.7% among those with compound mutations, and 60% among those with other mutations.
The most common grade ≥ 3 adverse events were diarrhea (22%), stomatitis/mucositis (8%), paronychia (7%), and appetite loss (7%) in the afatinib group and platelet decrease (14%), neutrophil decrease (11%), anemia (9%), and nausea (9%) in the chemotherapy group. Treatment-related death occurred in one patient in the afatinib group (from pneumonia).
The investigators concluded: “Afatinib should be considered the standard initial therapy for patients with NSCLC with sensitizing uncommon EGFR mutations.”
Satoru Miura, MD, PhD, of the Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Boehringer Ingelheim. For full disclosures of all study authors, visit the Journal of Clinical Oncology.
