medwireNews: The phase III ACHILLES/TORG1834 trial has confirmed that afatinib is superior to chemotherapy for treatment-naïve patients with nonsquamous small-cell lung cancer (NSCLC) and uncommon sensitising EGFR alterations.
Reporting the findings at the ESMO Congress 2023 in Madrid, Spain, Satoru Miura, from Niigata Cancer Center Hospital in Japan, said that the current study focused on the subgroup of patients with rare resistance mutations excluding the most frequently detected EGFR exon 20 insertion or de novo T790M alterations.
He explained that as these patients made up a small minority of participants in the LUX-Lung 2, 3 and 6 trials demonstrating afatinib efficacy, it has not been known if afatinib is the “optimal treatment” for these patients.
For the ACHILLES/TORG1834 trial, patients with locally advanced or metastatic disease including those with stable central nervous system (CNS) disease were recruited and randomly assigned to receive daily afatinib 40 mg or 30 mg (n=73) or platinum plus pemetrexed until disease progression (n=36).
The patient groups were “well balanced” for age, disease stage, smoking status and other characteristics, Satoru Miura said. Over two-thirds (68.5%) of patients had a single EGFR alteration, most commonly G719X (39.4%) or L861Q (18.3%), while 31.5% had a compound EGFR mutation made up of two uncommon alterations (22.0%) or one common and one uncommon alteration (9.2%).
The primary endpoint of progression-free survival (PFS), after a median of 12.5 months of follow-up, was significantly longer with afatinib than chemotherapy, at a median of 10.6 versus 5.7 months and a hazard ratio for progression or death of 0.42.
At 12 months, 42.1% of afatinib-treated patients were free from progression compared with 19.3% of controls, the presenter said, and all assessed patient subgroups had better PFS with afatinib than chemotherapy including those with CNS metastasis.
Patients in the afatinib arm also had a longer duration of treatment than their chemotherapy counterparts (median 10 vs 7 months), but the groups had comparable objective response rates (61.4 vs 47.1%) and disease control rates (82.9 vs 82.4%).
Turning to the safety summary, the presenter said that the profile was “consistent” with previous reports for afatinib and there were no new safety signals. Grade 3 and more severe adverse events (AEs) occurred in 43.8% and 37.1% of the afatinib and chemotherapy arms, respectively, with one pneumonitis-related death in the afatinib group.
The most common AEs at this severity with afatinib were diarrhoea (21.9%), mucositis (8.2%), paronychia (6.8%) and appetite loss (6.8%), whereas with chemotherapy, the most common grade 3 and more severe AEs were thrombocytopenia (14.3%), neutropenia (11.5%) and nausea (8.6%).
“The ACHILLES/TORG1834 study confirmed that afatinib is the standard treatment for patients with treatment-naïve nonsquamous NSCLC with sensitizing uncommon EGFR mutations”, Satoru Miura concluded.
“Additional data with overall survival, response according to detailed mutation status, and post-progression treatment profiles will eventually be available.”
Session discussant Fiona Blackhall, from the University of Manchester in the UK, said that a study to test afatinib in this patient subgroup was “long overdue” and commended the authors for allowing a lower dose afatinib treatment option and thus including patients who are frail or elderly.
Noting that afatinib is already approved for patients with uncommon sensitizing mutations, Fiona Blackhall said that the ACHILLES/TORG1834 findings are both “convincing” and “practice affirming” but that treatment progress in this patient population may “lag behind” those with more common alterations because of their routine exclusion from clinical trials.
Reference
LBA66 - Miura S, Tanaka H, Misumi T et al. Afatinib versus chemotherapy for treatment-naïve non-small cell lung cancer with a sensitizing uncommon epidermal growth factor receptor mutation: A phase III study (ACHILLES/TORG1834). Ann Oncol 2023;34:S2 (S1310–S1311). DOI: 10.1016/j.annonc.2023.10.067
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