An experimental lung cancer drug shrank tumors in 68% of untreated patients with a rare EGFR mutation

An experimental targeted drug, firmonertinib, shrank tumors in up to 68% of previously untreated patients with a rare form of lung cancer in a phase 1b trial, UT MD Anderson Cancer Center said on 16 October. The 60-patient FURTHER trial, published in Cancer Cell, included people with advanced non-small cell lung cancer driven by EGFR PACC mutations.

A mutation group that standard drugs were not built for

EGFR mutations are a common driver of non-small cell lung cancer. PACC mutations are a structurally distinct subgroup that makes up about 12% of EGFR-mutant non-small cell lung cancer, which itself accounts for 5% to 10% of all lung cancers. Responses to existing treatments can differ from those seen with the more common EGFR mutations.

Researchers have proposed grouping uncommon EGFR mutations by how they change the shape of the EGFR protein rather than by where they sit in the gene. The study found that a chemical feature of firmonertinib lets it bind more effectively to PACC-mutant proteins.

“Patients with uncommon EGFR mutations have long faced limited evidence to guide treatment decisions.” — Dr. Xiuning Le, MD Anderson, who led the trial

16 months before the disease worsened at the higher dose

Among previously untreated patients, 43% responded at 160 mg a day and 68% at 240 mg a day. Patients lived a median of 11.1 and 16 months without their disease worsening at the two doses. Of 17 patients whose cancer had spread to the brain, 47% saw brain tumors shrink and 41% had complete responses there. In 80% of evaluable patients, the PACC mutation disappeared from their blood, and those patients tended to do better.

What it means for patients now

Firmonertinib, developed by ArriVent BioPharma, which funded the study, is still experimental for this group of patients. Phase 1b trials are small and do not compare the drug with standard treatment, and MD Anderson's release does not report side effects; those are in the full paper. The results led to a global phase 3 trial, ALPACCA, which compares firmonertinib with osimertinib or afatinib as first treatment. It aims to enroll 480 patients and is recruiting, according to its ClinicalTrials.gov entry.

Patients with EGFR PACC mutations who want to know about trials should ask their oncologist. Other recent lung cancer research has focused on finding the disease earlier, such as blood markers that flagged risk up to 10 years before diagnosis.