Targeted Therapy for Lung Cancer: EGFR, ALK and What They Mean

Not all lung cancer is treated the same way. In non-small cell lung cancer (NSCLC), which accounts for roughly 85% of cases, the single most important question after diagnosis is no longer just the stage — it is which mutation is driving the tumour. That answer determines whether a patient is offered chemotherapy, immunotherapy, or a targeted tablet taken at home.

What is a driver mutation?

A driver mutation is a genetic change that the cancer depends on to keep growing. Where a tumour has one, a drug that blocks that specific change can be far more effective, and considerably gentler, than chemotherapy — which cannot tell a cancer cell from any other fast-dividing cell.

The drivers that matter most in NSCLC are EGFR, ALK, ROS1, BRAF, MET, RET and KRAS G12C. Each has at least one licensed therapy matched to it.

Why biomarker testing comes first

A targeted therapy only works if the target is there. Giving an EGFR inhibitor to someone without an EGFR mutation does not help, and delays treatment that would.

This is why guidelines recommend comprehensive biomarker testing — usually next-generation sequencing on a tissue biopsy, or a blood-based "liquid biopsy" where tissue is not available — before first-line treatment is chosen. Testing typically takes one to three weeks. It is worth the wait.

• Ask specifically whether full panel testing was done, not just EGFR
• Ask for a copy of the pathology and molecular report
• If tissue was insufficient, ask whether a liquid biopsy is possible

EGFR-mutated lung cancer

EGFR mutations are found in roughly 15% of NSCLC in European populations and 40-50% in East Asian populations — a difference large enough that testing is essential rather than optional.

Treatment is with an EGFR tyrosine kinase inhibitor. Third-generation agents such as osimertinib are generally preferred first-line: they cross into the brain, which matters because lung cancer commonly spreads there, and they are active against the T790M resistance mutation that limited earlier drugs.

Resistance still develops, usually within one to three years. When it does, repeat biopsy identifies the resistance mechanism and often opens a further line of treatment.

ALK-positive lung cancer

ALK rearrangements appear in about 3-5% of NSCLC, and disproportionately in younger patients and never-smokers. They are among the most treatable forms of advanced lung cancer.

Second- and third-generation ALK inhibitors — alectinib, brigatinib, lorlatinib — have largely replaced the first-generation crizotinib, again largely because of better control of brain metastases. Median progression-free survival on modern ALK inhibitors is measured in years rather than months.

ROS1, BRAF, MET, RET and KRAS

Each of these is individually uncommon, but collectively they cover a meaningful share of patients:

• ROS1 (1-2%) — entrectinib, crizotinib, repotrectinib
• BRAF V600E (2-4%) — dabrafenib with trametinib
• MET exon 14 skipping (3-4%) — capmatinib, tepotinib
• RET fusion (1-2%) — selpercatinib, pralsetinib
• KRAS G12C (about 13%) — sotorasib, adagrasib

A patient told "there is nothing targetable" before a full panel was run has not had the question properly answered.

Where immunotherapy fits

For tumours without a targetable driver, checkpoint inhibitors are usually the backbone of first-line treatment, alone or with chemotherapy, guided by PD-L1 expression. Our overview of how immunotherapy works covers this in more detail.

Notably, immunotherapy tends to work less well in EGFR- and ALK-driven tumours, which is another reason the testing sequence matters.

What this means practically

Targeted therapies are oral, taken continuously, and monitored with periodic scans and blood tests. Side effects differ by drug class — rash and diarrhoea are common with EGFR inhibitors, for instance — and are usually manageable with dose adjustment rather than stopping.

Supply continuity matters more than with a short course: these are taken daily for years, and interruptions are not harmless. If you are sourcing internationally, plan reorders well before you run out.

You can browse what we stock for lung cancer, or the wider oncology range.

Questions worth asking your oncologist

• Has comprehensive molecular testing been completed, and can I see the report?
• Is there a targeted therapy matched to my result?
• If I start this, what is the plan when resistance develops?
• Does this drug reach the brain?

This article is general information, not medical advice. Treatment decisions belong with a qualified clinician who knows your history. Every medicine mentioned is prescription-only and requires a valid prescription.