Targeted Therapy — Procedure Guide, Recovery & Risks | MyMedicPlus

Targeted therapy is a form of cancer treatment that uses drugs specifically designed to interfere with molecular targets — such as mutated proteins, growth factor receptors, or signalling pathways — that cancer cells rely on to grow and survive. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, targeted agents act on specific cancer vulnerabilities, causing fewer off-target side effects while achieving potent anti-cancer activity. Targeted therapy is preceded by biomarker testing (next-generation sequencing, immunohistochemistry, or liquid biopsy) to identify the actionable mutation driving tumour growth.

Targeted therapy works by interfering with specific molecular 'drivers' of cancer growth: small molecule inhibitors cross cell membranes to block intracellular kinases and signalling enzymes; monoclonal antibodies bind to surface receptors or circulating growth factors; and antibody-drug conjugates (ADCs) deliver cytotoxic payloads directly to cancer cells. Comprehensive genomic profiling (next-generation sequencing of tumour DNA) now identifies dozens of actionable alterations across tumour types, enabling precision matching of therapy to tumour biology regardless of tumour site of origin ('tumour-agnostic' approvals). Targeted therapy has transformed the prognosis of multiple cancers including EGFR-mutant lung cancer, HER2-positive breast cancer, BCR-ABL-positive leukaemia, and BRAF-mutant melanoma — achieving far superior outcomes to chemotherapy in biomarker-selected patients.

Targeted therapy is used when tumour biomarker testing identifies a specific molecular driver mutation. Common targets include EGFR mutations in non-small cell lung cancer (osimertinib), HER2 amplification in breast cancer (trastuzumab, pertuzumab), BRAF V600E in melanoma (vemurafenib plus cobimetinib), ALK/ROS1 rearrangements in lung cancer (crizotinib, alectinib), BCR-ABL fusion in CML (imatinib), and VEGFR in kidney and liver cancers (sunitinib, sorafenib). Comprehensive molecular profiling by an oncology multidisciplinary team guides selection of the most appropriate targeted agent for each patient's unique tumour profile.

Targeted therapy is now standard of care in multiple cancer types when specific alterations are identified: osimertinib for EGFR-mutant NSCLC; alectinib or lorlatinib for ALK-rearranged NSCLC; trastuzumab plus pertuzumab for HER2-positive breast cancer; imatinib for BCR-ABL-positive CML and KIT-mutant GIST; dabrafenib plus trametinib for BRAF V600E-mutant melanoma and NSCLC; olaparib for BRCA1/2-mutated ovarian and breast cancer; larotrectinib for NTRK fusion-positive cancers (any tumour site); and pembrolizumab for tumour mutational burden-high (TMB-H) or MSI-high/dMMR solid tumours regardless of histology.

Before starting, tumour biopsy tissue or circulating tumour DNA (liquid biopsy) is analysed by molecular pathology to identify actionable mutations. If a target is present, the appropriate drug is selected. Small molecule inhibitors (TKIs such as erlotinib, imatinib, lapatinib) are taken as daily oral tablets at home. Monoclonal antibodies (trastuzumab, bevacizumab, cetuximab) are administered as IV infusions every 1-3 weeks in an outpatient oncology unit over 30-90 minutes. Pre-medication with antihistamines and corticosteroids reduces infusion reaction risk. Treatment continues until disease progression or unacceptable toxicity, with response assessment by CT or PET-CT every 8-12 weeks.

Liquid biopsy (circulating tumour DNA from a blood sample) can detect actionable mutations non-invasively and is particularly valuable for monitoring acquired resistance mutations during treatment. Most targeted therapies are administered orally as daily tablets or capsules, enabling outpatient treatment without hospital admission. Intravenous targeted therapies (trastuzumab, cetuximab, ramucirumab) are given as day-case infusions every 1–3 weeks. Treatment continues until disease progression, unacceptable toxicity, or patient decision. Biomarker testing by next-generation sequencing (NGS) identifies driver mutations, fusions (ALK, ROS1, RET, NTRK), amplifications (HER2, MET), and tumour mutational burden (TMB) to guide optimal therapy selection. Liquid biopsy (ctDNA) enables monitoring of treatment response and detection of emerging resistance mechanisms without repeat tissue biopsy, guiding earlier therapy switches.

Targeted therapy has transformed outcomes for biomarker-selected patients. EGFR-mutant NSCLC treated with osimertinib achieves median PFS of 18.9 months versus 10.2 months for chemotherapy. ALK-rearranged NSCLC with lorlatinib achieves 5-year PFS of 60% — unprecedented in advanced NSCLC. HER2-positive breast cancer with trastuzumab plus pertuzumab achieves 5-year OS of 57% in metastatic disease, compared to under 20% with chemotherapy alone historically.

BCR-ABL-positive CML treated with imatinib or second-generation TKIs achieves 10-year survival of over 80%, with many patients now expecting near-normal life expectancy. BRAF V600E melanoma treated with dabrafenib plus trametinib achieves 5-year OS of 34% versus less than 10% historically. These outcomes represent transformational advances in oncology and are the basis for precision medicine. Combined targeted therapies (EGFR-TKI plus anti-VEGF bevacizumab; BRAF plus MEK inhibitor combination) delay resistance by simultaneously attacking multiple oncogenic pathways, achieving superior outcomes to single-agent targeted therapy.

Drug-specific side effects include EGFR inhibitor-related skin rash (70-80%), anti-HER2 agent cardiotoxicity (5-10% left ventricular dysfunction), VEGFR inhibitor hypertension and hand-foot syndrome, BRAF inhibitor-induced secondary cutaneous squamous cell carcinoma (15-30%), and ALK inhibitor visual disturbance. Acquired resistance develops in most patients within 1-3 years, requiring rebiopsy to guide switch to next-generation agents. Rare but serious toxicities include interstitial lung disease with some TKIs and hepatotoxicity requiring dose interruption.

Acquired resistance to targeted therapy is a near-universal challenge: the median progression-free survival on EGFR-TKI first-line therapy is 18–24 months before resistance emerges. Resistance mechanisms include secondary EGFR T790M mutation (targetable with osimertinib), MET amplification, RAS mutation, and histological transformation. Re-biopsy at progression is essential to identify the resistance mechanism and guide subsequent therapy. Immune-mediated adverse events from newer immunomodulatory targeted agents require prompt recognition and management with corticosteroids.

Targeted therapy is generally well tolerated compared to chemotherapy and most patients maintain near-normal daily activities during treatment. Common side effects — rash, diarrhoea, fatigue, hypertension, hand-foot syndrome — are managed with dose adjustments, topical treatments, and supportive care. Blood tests, imaging (CT or PET scans), and tumour marker monitoring every 6-12 weeks assess response. ECHO or MUGA scans monitor cardiac function for HER2-directed therapies every 3 months. Skin care routines, blood pressure monitoring, and dietary modifications for hand-foot syndrome are provided at treatment initiation. Patient education on recognising early signs of toxicity is essential.

Patients on oral targeted therapies require regular monitoring: LFTs, full blood count, renal function, and electrocardiogram (QTc monitoring for some agents) at monthly intervals. Skin and nail toxicities from EGFR inhibitors require proactive management: pre-emptive tetracycline antibiotics reduce rash severity and support maintained treatment adherence. Emollient skin care, avoiding sun exposure, and using gentle skin cleansers reduce EGFR inhibitor skin toxicity. Diarrhoea management with loperamide and dietary adjustment enables continuation of therapy that would otherwise require dose reduction.