Targeted Therapy vs Chemotherapy — Clinical Trial Comparison
Targeted Therapy
Drugs targeting specific molecular features of cancer
VS
Chemotherapy
Cytotoxic drugs killing rapidly dividing cells
Targeted therapy and chemotherapy both aim to destroy cancer cells, but they work in fundamentally different ways. Targeted therapies zero in on specific molecular features of a tumour — a mutated gene, an overexpressed protein, or a signalling pathway — while chemotherapy attacks all rapidly dividing cells. The shift toward targeted therapy is one of the biggest stories in modern oncology, and UK clinical trials are at the forefront of this transformation.
Key Differences at a Glance
| Feature | Targeted Therapy | Chemotherapy |
|---|---|---|
| Mechanism | Blocks specific molecules or pathways essential for tumour growth and survival | Directly damages DNA or disrupts cell division in all rapidly dividing cells |
| Target specificity | Highly specific — requires identifiable molecular target (mutation, amplification, fusion) | Non-specific — affects all proliferating cells (cancer and normal) |
| Genetic testing required | Yes — molecular profiling (NGS, FISH, PCR) is essential before treatment | Usually not — though increasingly used to guide chemo choices |
| Common targets in trials | EGFR, ALK, ROS1, BRAF, HER2, KRAS G12C, NTRK, RET, MET, FGFR | No specific molecular target needed |
| Side effect profile | Generally milder but specific to target (rash, diarrhoea, cardiac, liver) | Broader toxicity — nausea, hair loss, myelosuppression, neuropathy |
| Administration | Often oral (daily tablets) or IV | Usually IV infusion in cycles (every 1–3 weeks) |
Clinical Trial Availability
| Trial Aspect | Targeted Therapy | Chemotherapy |
|---|---|---|
| UK trials actively recruiting | 300–500 studies | 150–250 studies |
| Most common phases | Phase 1–3 (basket and umbrella trials common) | Phase 2–3 |
| Top cancers studied | Lung cancer (NSCLC), breast cancer, colorectal, melanoma, thyroid | Breast, lung, colorectal, ovarian, pancreatic, gastric |
| Biomarker-driven trials | Almost all require molecular profiling | Some require specific markers, many do not |
| Novel trial designs | Basket trials, umbrella trials, N-of-1, master protocols | Traditional randomised controlled trials predominate |
| Resistance mechanisms studied | Secondary mutations, bypass signalling, histologic transformation | Drug resistance less specifically studied |
Exciting Emerging Treatments
Targeted Therapy Trials
- KRAS G12C inhibitors — targeting the "undruggable" KRAS mutation
- Proteolysis-targeting chimeras (PROTACs) — degrading disease-causing proteins
- Next-gen HER2-targeted agents — HER2-low breast cancer, HER2-mutant lung
- Tumour-agnostic therapies — targeting mutations regardless of cancer type
- Combination targeted therapy — hitting multiple pathways simultaneously
- Adaptive trial designs — real-time biomarker-driven treatment switching
Chemotherapy Trials
- Antibody-drug conjugates — attaching chemo to antibodies for precision delivery
- Nanoparticle delivery — reducing systemic chemo toxicity
- Metronomic dosing — continuous low-dose anti-angiogenic approach
- Chemo + immunotherapy — chemo as immune primer
- Organoid-guided chemo selection — personalised drug sensitivity testing
- Dose-optimisation trials — finding minimum effective doses
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Eligibility Differences
Targeted Therapy Trial Criteria
- Documented molecular alteration matching the trial drug target
- Next-generation sequencing (NGS) or FISH confirmation required
- Prior treatment history appropriate for line of therapy
- Measurable disease per RECIST v1.1
- Adequate organ function
- No concurrent targeted therapies that may interact
Chemotherapy Trial Criteria
- Confirmed cancer diagnosis with measurable disease
- Adequate blood counts, renal and hepatic function
- ECOG performance status 0–2
- No uncontrolled comorbidities
- Recovery from prior treatment toxicities
- Appropriate prior treatment for line of therapy
Targeted Therapy Trials
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Targeted Therapy TrialsCancer Condition Trials
Browse all cancer conditions with active UK clinical trials
Cancer Condition TrialsFrequently Asked Questions
Do I need genetic testing before joining a targeted therapy trial?
Yes, virtually all targeted therapy trials require molecular profiling. This typically means next-generation sequencing (NGS) of your tumour tissue, and sometimes blood-based liquid biopsy. Without identifying a targetable mutation, targeted therapy cannot work. Your oncologist can arrange this testing.
Is targeted therapy better than chemotherapy?
Not necessarily better — different. Targeted therapy can be more effective and better tolerated when a matching molecular target exists, but not all cancers have actionable targets. Many patients benefit from both approaches, and combination regimens are increasingly common in trials.
What are tumour-agnostic trials?
Tumour-agnostic trials treat the genetic mutation rather than the cancer type. For example, a NTRK fusion inhibitor trial might enrol patients with lung cancer, thyroid cancer, or sarcoma — as long as they share the NTRK fusion. These are some of the most innovative trials available.