Treating itLung cancer (all types)

Annual low-dose CT for people aged about 50 to 80 with a heavy smoking history (NLST, NELSON).

CT, PET-CT, bronchoscopy or CT-guided biopsy, endobronchial ultrasound of nodes, brain MRI; molecular testing on every non-squamous non-small-cell tumour.

By type and stage on the subtype pages: surgery or stereotactic radiotherapy for early disease, chemoradiation with immunotherapy for locally advanced, targeted or immune therapy for metastatic disease.

Refer on the suspected cancer pathway for chest X-ray findings that suggest lung cancer, or for unexplained haemoptysis at 40 and over. Offer an urgent direct access chest X-ray at 40 and over for two or more of cough, fatigue, shortness of breath, chest pain, weight loss and appetite loss, or for one of them in anyone who has ever smoked. Consider one for persistent or recurrent chest infection, finger clubbing, supraclavicular or persistent cervical lymphadenopathy, chest signs consistent with lung cancer, or thrombocytosis. Mesothelioma has its own rules in the same section, with asbestos exposure lowering the threshold.

Tobacco control and stopping smoking, which is the only lever that reaches the 72 percent of UK cases caused by smoking. NICE NG209 covers preventing uptake in people aged 24 and under and treating dependence in everyone aged 12 and over, and was updated in February 2025 to add cytisinicline. Screening services carry smoking cessation with them, as the UK National Screening Committee required. Radon can be measured in a home and reduced; workplace exposures are regulated.

For lung cancer that has not spread, the first question is not which treatment is strongest but which treatment your lungs can afford. NICE NG122 (1.5.1) says that for people who are well enough and for whom treatment with curative intent is suitable, offer lobectomy, either open or thoracoscopic, and (1.5.2) offer more extensive surgery only where it is needed to get clear margins. NICE's own explanation is that lobectomy gives better survival than stereotactic ablative radiotherapy and is a good compromise between preserving lung function and removing the cancer. The fitness assessment runs on numbers rather than on impressions: spirometry and transfer factor before any treatment with curative intent (1.4.9), a functional segment count to predict lung function after the operation (1.4.11), a shuttle walk test with 400 m as the cut-off for good function or an exercise test with 15 ml/kg/minute where the risk of breathlessness afterwards is moderate to high (1.4.13 and 1.4.14), and a global risk score such as Thoracoscore with the person told the risk before they consent (1.4.1). Where predicted lung function after surgery is low, the guideline does not close the door: it says to offer people with a predicted postoperative FEV1 or transfer factor below 30 percent the option of treatment with curative intent if they accept the risks of breathlessness and associated complications (1.4.12). Two branches follow. If you decline a lobectomy or it is contraindicated, NICE offers stereotactic ablative radiotherapy or a sublobar resection (1.5.5), and says the evidence does not establish which of those two is better. If you decline any surgery or none is possible, it offers stereotactic ablative radiotherapy, and conventional or hyperfractionated radiotherapy if that is contraindicated (1.5.8). Stereotactic radiotherapy is outpatient treatment over a handful of visits, which is why people often prefer it. Smoking sits inside this row rather than beside it: NICE says to explain that smoking increases the risk of lung complications after surgery and to advise stopping as soon as the diagnosis is suspected, and in the same section says not to postpone surgery to allow people to stop (1.3.1 to 1.3.3).

An operation is rarely the whole of the treatment for anything above the smallest tumours, and the order matters. Before surgery, NICE NG122 (1.6.8) recommends nivolumab with chemotherapy for neoadjuvant treatment of resectable disease at least 4 cm or node positive, and (1.6.9 and 1.6.10) durvalumab or pembrolizumab with platinum chemotherapy given before and then continued after the operation, durvalumab restricted to disease without EGFR mutations or ALK rearrangements. That restriction is why the molecular result has to be back before this decision is made rather than after it. After surgery, NICE (1.6.11) says to offer systemic anticancer therapy to people with good performance status and T1a to 4, N1 to 2, M0 disease, (1.6.12) to consider it for T2b to 4, N0, M0 tumours larger than 4 cm, and (1.6.13) to use a platinum-based combination. Where a targetable change is present the adjuvant treatment is a tablet instead: osimertinib after complete resection of stage 1b to 3a EGFR exon 19 deletion or L858R disease, stopped at 3 years or earlier on recurrence or unacceptable toxicity (1.6.14), and alectinib after complete resection of stage 1b (at least 4 cm) to 3a ALK-positive disease (1.6.15). For operable stage 3a N2 disease NICE (1.6.3 to 1.6.6) says to consider chemoradiotherapy with surgery, to discuss the benefits and risks first including that it improves progression-free survival and may improve overall survival, to schedule the operation 3 to 5 weeks after the chemoradiotherapy finishes so there is time to recover, and to do it only in teams with expertise in the combined treatment and in each of its parts. The practical questions this row generates are about sequence and waiting: what has to come back before we decide, how long the treatment before surgery adds, and what the pathology report will change afterwards.

Locally advanced lung cancer is the stage where the treatment is hardest and the intent is still cure. NICE NG122 (1.6.17) says to consider chemoradiotherapy for people with stage 2 or 3 disease whose condition is not suitable for surgery or who decline it, and to balance the potential survival benefit against the risk of additional toxicities, which is an unusually honest sentence for a guideline and worth quoting back in clinic. What follows the chemoradiotherapy is now part of the plan rather than an afterthought: NICE (1.6.18) recommends durvalumab for locally advanced unresectable disease with PD-L1 expression on 1 percent or more of tumour cells where the disease has not progressed after concurrent platinum-based chemoradiation; the schedule this came from, PACIFIC, gave it for a year. For people whose tumour carries an EGFR change, the corpus records LAURA, which tested osimertinib in the same position after chemoradiotherapy, so what is offered depends on both the PD-L1 result and the gene result and is worth asking about by name. Where chemoradiotherapy is too much, NICE (1.5.9 and 1.5.10) says to consider radical radiotherapy, conventional or hyperfractionated, for people with stage 3a or 3b disease who are eligible, while saying plainly that some people who cannot tolerate chemoradiotherapy will not manage radical radiotherapy either. The side effect that defines this row is inflammation of the lung: both the radiotherapy and the immunotherapy can cause it, the symptoms are identical (breathlessness, a cough that does not go away, wheezing, a fever over 37.5 C), and Macmillan's instruction for all of them is the same, which is to ring the 24-hour number straight away rather than wait for the next clinic.

Once lung cancer has spread, the tumour's genes decide the first treatment more completely than in almost any other cancer, and the honest advice is usually to wait for the result. NICE NG122 (1.2.12) says to see the National Genomics Test Directory for guidance on next-generation sequencing panels to guide treatment, and (1.2.11) that samples must be adequate, without unacceptable risk to the person, to permit subtyping and assessment of molecular markers. The genes with a treatment attached that the record carries are EGFR, ALK, ROS1, KRAS G12C, BRAF V600, MET exon 14 skipping, RET fusions, HER2 mutations and NTRK fusions, and for most of them the matched tablet does better than what would otherwise be given first. The case for waiting is not only that a targeted drug might be missed. Some of the immunotherapy recommendations are written to exclude EGFR and ALK disease (NICE 1.6.9 does so explicitly for durvalumab around surgery), and a treatment started in the wrong lane is harder to undo than a fortnight of waiting. The case against waiting is real too, and belongs in the conversation: if someone is unwell, losing weight quickly or in pain, a team may sensibly start something now and change when the result lands. That is a judgement about the person, not a failure of the system, and the question to ask is what would be started and how fast the switch could happen. Where tissue is short, a blood test for circulating tumour DNA can sometimes answer sooner; it cannot show a change in how the cancer looks under the microscope, so it complements a biopsy rather than replacing it.

Where no targetable change is found, the first treatment for advanced lung cancer is immunotherapy, and the PD-L1 score decides whether it is given alone or with chemotherapy. NICE NG122 organises its published treatment pathways for advanced disease around exactly this split, separately for squamous and non-squamous cancer: no targetable mutations with PD-L1 below 50 percent, and no targetable mutations with PD-L1 at 50 percent or higher, with further pathways for RET fusion, KRAS G12C, MET exon 14 skipping and BRAF V600 disease at each PD-L1 level. In practice a high score opens the option of a checkpoint antibody on its own, which is a gentler treatment with fewer visits and no hair loss; adding chemotherapy works faster and is usually preferred when there is a lot of disease, when symptoms are pressing, or when the score is low. Neither is a better treatment in the abstract, and the question worth asking is which of those considerations is driving the recommendation for you. The trade-off in side effects is different in kind rather than in degree. Chemotherapy's effects are mostly predictable and temporary; immune effects are less predictable, can affect any organ, and Macmillan says they can begin during treatment or after it ends, which is why the alert card is issued and why the same short list is repeated at every visit: breathlessness, a new cough, wheezing or a fever over 37.5 C; more stools than is normal for you or stools at night; a spreading, blistering or peeling rash with flu-like symptoms; and feeling unwell even with a normal temperature.

Targeted tablets work until the cancer finds a way round them, and planning for that in advance makes the day it happens less frightening. The first thing to establish is the pattern. One growing area with everything else stable is often treated locally, with stereotactic radiotherapy to that spot and the tablet continued; growth in several places usually means changing treatment. The second is whether to look at the cancer again. NICE NG122 (1.2.11) asks for samples adequate to permit pathological diagnosis including subtyping and assessment of molecular markers, and (1.2.13) to choose investigations that give the most information with the least risk to the person, thinking carefully before performing a test that gives only diagnostic pathology when other information is needed too. Applied at resistance, that is the argument for and against a repeat biopsy: it can show a new resistance mutation, an amplified second gene, or that the cancer has transformed into a different type entirely, and each of those points somewhere different. A blood test for tumour DNA is quicker and can find a new mutation, but it cannot see a transformation, so where that is the question tissue is still needed. What follows depends on what is found: a next-generation inhibitor of the same target, chemotherapy with or without an antibody, an antibody drug conjugate such as patritumab deruxtecan in the HERTHENA-Lung02 setting, or a trial. Trials usually require you to be well enough to take part, so this is the point at which to ask for the referral rather than several months later.

Lung cancer reaches the brain more often than most cancers, and the treatment has changed enough that old assumptions are worth putting down. NICE NG122 (1.16.1) says to offer dexamethasone to people with symptomatic brain metastases and to reduce to the minimum necessary maintenance dose for symptomatic response, and (1.16.2) refers the treatment itself to the section on management of confirmed brain metastases in its brain tumours guideline rather than repeating it. The practical choice is between focused radiotherapy to a small number of spots, whole-brain radiotherapy, surgery for a single accessible lesion, and, increasingly, a targeted tablet chosen because it crosses into the brain: several of the modern drugs recorded here were designed to do so, which can mean treating brain disease with tablets rather than radiotherapy. NICE is willing to say out loud that radiotherapy to the whole brain has a cost: writing about preventive brain radiotherapy in small-cell disease it says the treatment can adversely affect quality of life and that the survival benefits are limited. Which approach is proposed, and why, is therefore a reasonable question. The symptoms to know, from Cancer Research UK, are memory problems, mood or personality changes, seizures, confusion, severe headaches often with sickness, and weakness of an arm or a leg. Two practical matters usually go unmentioned until they bite. Driving is governed by DVLA rules after a seizure or a brain metastasis and is worth asking about before it is assumed either way. Steroids lift symptoms quickly but have their own effects, and NICE NG122 (1.16.1) says to reduce to the minimum necessary maintenance dose for symptomatic response, so the plan to come down matters as much as the plan to start.

Lung cancer has more trials open than almost any other cancer, because the targets keep multiplying, and at several points a trial is a reasonable choice beside standard treatment rather than a last resort. The open questions this record follows are the ones a trial would answer for you: whether immunotherapy before surgery should be continued afterwards and for how long; whether stereotactic radiotherapy matches surgery for a small tumour in someone fit for either, which NICE itself has written as a research recommendation; what to give after a third-generation EGFR inhibitor stops working; whether treating a single growing spot buys more time on the same tablet; and whether preventive brain radiotherapy in small-cell disease can be replaced by regular MRI scans, another NICE research recommendation. The NHS is the plainest source on what taking part involves: you can ask your doctor or a patient organisation about trials you may be eligible to join; you will usually be randomly assigned either to the treatment being assessed or to a control group given standard treatment, or a placebo where no proven standard exists; trials can be time consuming, with screening and follow-up visits and sometimes overnight stays; some cover travel expenses; and you can choose to leave at any point without giving a reason and without it affecting the care you receive. Ask early rather than late, because most trials require you to be well enough to take part.

Palliative care means symptom control and support, and it is not a stage of the illness. In lung cancer this is not an opinion: it is one of the few places in oncology where starting supportive care early was tested in a randomised trial and improved survival. Temel and colleagues (NEJM 2010) randomly assigned 151 people with newly diagnosed metastatic non-small-cell lung cancer to early palliative care integrated with standard oncology care, or to standard oncology care alone. At 12 weeks the early palliative care group had better quality of life (mean FACT-L 98.0 against 91.5, P equals 0.03) and fewer depressive symptoms (16 against 38 percent, P equals 0.01); fewer received aggressive care at the end of life (33 against 54 percent, P equals 0.05), and median survival was longer (11.6 against 8.9 months, P equals 0.02). That result is why the referral is offered alongside treatment rather than after it. NICE NG122 fills in what the service does: palliative radiotherapy as symptoms arise or immediately for people who cannot have curative treatment (1.13.1); radiotherapy, debulking or a stent for an airway that is closing (1.14.2); draining a pleural effusion and talc pleurodesis where that would give lasting benefit (1.15.1 and 1.15.2); breathing control, psychosocial support and coping strategies for breathlessness, delivered by people with expertise in the techniques and available in all care settings (1.15.3 and 1.15.4); opioids such as codeine or morphine to reduce cough (1.15.5); chemotherapy and radiotherapy, and a stent where symptoms are severe, for superior vena cava obstruction (1.15.7 and 1.15.8); dexamethasone for symptomatic brain metastases (1.16.1); single-fraction radiotherapy for bone pain that ordinary painkillers are not controlling (1.17.1); and multidisciplinary management of weight loss, appetite, swallowing and depression (1.18.1). Marie Curie adds that it can start at any point and can run alongside chemotherapy or radiotherapy, and that it also supports the people close to you.

Annual low-dose CT of the chest in current and former smokers of the eligible age and pack-year range, with volume-based nodule management. NLST (53,454 participants) showed a 20 percent relative reduction in lung cancer mortality against chest radiography, and NELSON (15,789) a 24 percent reduction in men at ten years with a lower false-positive rate. In England the Targeted Lung Health Check programme invites people aged 55 to 74 with a smoking history. Screening is the single intervention with the largest effect on lung cancer mortality, and uptake, not evidence, is the limiting factor.

Anatomical resection with mediastinal lymph node dissection or sampling. For a peripheral tumour 2 cm or smaller, sublobar resection is now a standard option rather than a compromise: JCOG0802/WJOG4607L found segmentectomy superior to lobectomy for overall survival (in the radiologically pure-solid subgroup, five-year overall survival 92.4 against 86.1 percent, hazard ratio 0.64), and CALGB 140503 found sublobar resection non-inferior for disease-free survival in 697 patients. Adjuvant chemotherapy is not given: the LACE pooled analysis found a hazard ratio of 1.40 in stage IA, so it is avoided, and stage IB gains little. Video-assisted or robotic access is preferred where expertise exists.

Stereotactic ablative radiotherapy, typically 54 Gy in three fractions or an equivalent schedule adapted to tumour position. CHISEL randomised 101 patients with inoperable peripheral stage I disease to stereotactic or conventional radiotherapy and found better local control and overall survival with the stereotactic schedule. Whether it can replace an operation in fit patients is unsettled: the pooled STARS and ROSEL analysis favoured radiotherapy (three-year overall survival 95 against 79 percent), but on 58 patients from two trials that closed early, and the larger randomised comparisons have not reported. Thermal ablation is an alternative for small tumours where radiotherapy is not possible.

Four cycles of cisplatin with vinorelbine, or another cisplatin doublet, starting six to twelve weeks after surgery. IALT (1,867 patients) gave five-year survival 44.5 against 40.4 percent, JBR.10 established the cisplatin and vinorelbine regimen, and ANITA gave median survival 65.7 against 43.7 months. The LACE pooled analysis of 4,584 patients set the modern indication: hazard ratio 0.89 overall, a 5.4 percent absolute five-year benefit, rising with stage (stage II 0.83, stage III 0.83) and absent, with a point estimate favouring observation, in stage IA. Carboplatin is substituted where cisplatin is contraindicated, on weaker evidence. Postoperative mediastinal radiotherapy is not given for N2 disease after a complete resection: Lung ART did not improve three-year disease-free survival and increased cardiopulmonary toxicity.

For an EGFR exon 19 deletion or L858R, osimertinib after resection and any adjuvant chemotherapy. ADAURA improved disease-free and overall survival, and the 2026 exploratory long-term analysis gives eight-year overall survival of 74 against 58 percent in stage II to IIIA (hazard ratio 0.53) and 79 against 64 percent in stage IB to IIIA (0.52), with the benefit larger for exon 19 deletions (0.45) than L858R (0.72). In England NICE TA1043 funds it but requires that it stops at three years. For ALK-positive disease, two years of alectinib after resection of stage IB (4 cm or more) to IIIA disease, on ALINA (disease-free survival hazard ratio 0.24), FDA-approved in 2024; overall survival is immature. Adjuvant immunotherapy is not given alongside either: EGFR- and ALK-altered tumours were excluded from or did not benefit in the immunotherapy trials.

Three or four cycles of platinum doublet chemotherapy with a checkpoint inhibitor before surgery, and in most schedules the checkpoint inhibitor alone for a year afterwards. CheckMate 816 gave neoadjuvant nivolumab with chemotherapy alone (median event-free survival 31.6 against 20.8 months, hazard ratio 0.63; pathological complete response 24.0 against 2.2 percent). The perioperative schedule adds adjuvant treatment: KEYNOTE-671 with pembrolizumab, AEGEAN with durvalumab (event-free survival hazard ratio 0.69), CheckMate 77T with nivolumab (18-month event-free survival 70.2 against 50.0 percent, hazard ratio 0.58), Neotorch with toripalimab in stage III disease (hazard ratio 0.40) and RATIONALE-315 with tislelizumab (overall survival hazard ratio 0.65). Whether the adjuvant half adds anything to the neoadjuvant half is the open question; no trial has tested it directly. Tumours with EGFR or ALK alterations are excluded. Adjuvant-only immunotherapy after chemotherapy remains an option where surgery came first: atezolizumab in PD-L1-positive stage II to IIIA disease (IMpower010) or pembrolizumab (KEYNOTE-091).

Concurrent platinum-based chemoradiotherapy to 60 Gy, then consolidation. RTOG 0617 showed that raising the dose to 74 Gy shortens survival, so 60 Gy is the ceiling. For disease without an EGFR mutation, a year of durvalumab: PACIFIC gave 24-month overall survival 66.3 against 55.6 percent (hazard ratio for death 0.68) and median progression-free survival 17.2 against 5.6 months, with the benefit holding at five years. Concurrent, rather than consolidation, immunotherapy failed in PACIFIC-2. Where chemoradiotherapy had to be given sequentially, GEMSTONE-301 showed consolidation sugemalimab still works (median progression-free survival 9.0 against 5.8 months), although that drug is licensed only in China and the EU. For EGFR-mutant stage III disease, osimertinib instead of durvalumab, on LAURA, funded in England under NICE TA1156.

Comprehensive molecular profiling, by next-generation sequencing of tissue and, where tissue is inadequate or time is short, of plasma, plus PD-L1 immunohistochemistry. The minimum set is EGFR (including exon 20 insertions and the uncommon G719X, L861Q and S768I), ALK, ROS1, KRAS G12C, MET exon 14 skipping, RET, BRAF V600E, HER2 and NTRK, with NRG1 where a targetable fusion is suspected and none is found. Starting immunotherapy before the result is known is the commonest avoidable error: an EGFR- or ALK-driven tumour rarely responds to it, and giving a checkpoint inhibitor shortly before osimertinib raises the risk of severe pneumonitis and hepatotoxicity. PD-L1 assays are not interchangeable: KEYNOTE-024 used 22C3 with a tumour proportion score, IMpower110 used SP142 scoring both tumour and immune cells.

Osimertinib alone (FLAURA: median progression-free survival 18.9 against 10.2 months, hazard ratio 0.46; median overall survival 38.6 against 31.8 months), or intensified first-line treatment for patients with heavier disease: osimertinib with pemetrexed and platinum chemotherapy (FLAURA2) or amivantamab with lazertinib (MARIPOSA), both funded in England under TA1060 and TA1122. Dacomitinib (ARCHER 1050: 14.7 against 9.2 months against gefitinib) and afatinib (LUX-Lung 3: 13.6 against 6.9 months in the common mutations) remain licensed alternatives. At progression, plasma or tissue is re-tested for MET amplification, C797S, small-cell transformation and other mechanisms; historically T790M after a first-generation drug was treated with osimertinib (AURA3: 10.1 against 4.4 months), a sequence first-line osimertinib has largely removed.

Exon 20 insertions do not respond to osimertinib. First line, amivantamab with carboplatin and pemetrexed (PAPILLON), available in England only through a managed access period under NICE TA1158; amivantamab alone after platinum chemotherapy is approved by the FDA but not recommended by NICE (TA850). Mobocertinib was withdrawn worldwide in 2023 after its confirmatory trial failed. For the non-resistant uncommon mutations G719X, L861Q and S768I, afatinib holds a specific FDA indication granted in January 2018 on a pooled analysis of LUX-Lung 2, 3 and 6, and is preferred to osimertinib.

A later-generation ALK inhibitor first, never crizotinib. Lorlatinib has the longest disease control recorded for any targeted lung cancer drug: in CROWN, five-year progression-free survival was 60 against 8 percent with crizotinib (hazard ratio 0.19), with intracranial progression close to abolished, at the cost of neurocognitive, mood, weight and lipid effects. Alectinib (ALEX: median progression-free survival 34.8 against 10.9 months; ALESIA in Asian patients) and brigatinib (ALTA-1L) are the alternatives. Crizotinib, which PROFILE 1014 established against chemotherapy (10.9 against 7.0 months), is now the control arm rather than a treatment. In England NICE funds lorlatinib (TA1103), brigatinib (TA670), alectinib (TA536) and ceritinib (TA500) first line, and lorlatinib (TA628) or brigatinib after crizotinib (TA571) later.

Repotrectinib or entrectinib first line, because both cross into the brain. TRIDENT-1 gave a 79 percent response rate and median progression-free survival of 35.7 months in ROS1 inhibitor-naive patients, and responses in 59 percent of those with the G2032R solvent-front mutation after an earlier inhibitor. Crizotinib, which defined the subtype (72 percent response, median progression-free survival 19.2 months in the PROFILE 1001 expansion cohort), penetrates the brain poorly and is a second choice; taletrectinib is approved in China and the United States. In England NICE recommends crizotinib (TA1021) and entrectinib (TA643) and asks for the least expensive; there is no appraisal of repotrectinib for this indication.

Chemotherapy with immunotherapy first line, then a KRAS G12C inhibitor. Sotorasib (CodeBreaK 200) and adagrasib (KRYSTAL-12) both beat docetaxel on progression-free survival in the second line without an overall survival gain, which is why the class is second line rather than first. In England sotorasib is available only through the Cancer Drugs Fund under a managed access agreement (NICE TA781) and adagrasib has no recommendation. Divarasib and olomorasib, which bind the same pocket with better exposure, and the RAS(ON) inhibitors that also cover the non-G12C alleles, are in phase 3. Liver enzyme rises are the characteristic toxicity and are worse when a KRAS inhibitor follows a checkpoint inhibitor closely.

Tepotinib or capmatinib for MET exon 14 skipping, on the single-arm VISION and GEOMETRY mono-1 trials; in England NICE TA789 recommends tepotinib and there is no appraisal of capmatinib. Peripheral oedema is the characteristic and often dose-limiting toxicity. For MET-amplified disease arising as resistance to an EGFR inhibitor, savolitinib with osimertinib is approved in China; telisotuzumab vedotin, an antibody-drug conjugate against c-Met, was approved by the FDA in 2025 for previously treated c-Met-high non-squamous disease.

Selpercatinib. LIBRETTO-431 established it against platinum chemotherapy with or without pembrolizumab in untreated disease, and LIBRETTO-001 gave an objective response of 85 percent in the untreated and 64 percent in the previously treated, with 91 percent intracranial response. In England NICE TA911 gives untreated patients access through managed access and TA1042 recommends it routinely after previous treatment. Pralsetinib produced a 61 percent response in the previously treated cohort of ARROW but is not recommended by NICE (TA812), so selpercatinib is effectively the only funded option in England.

BRAF V600E: dabrafenib with trametinib (64 percent response in the untreated cohort of BRF113928) or encorafenib with binimetinib (PHAROS); both are funded in England first line only, under NICE TA898 and TA1150. HER2 (ERBB2) mutation: trastuzumab deruxtecan at 5.4 mg/kg (DESTINY-Lung02), with interstitial lung disease as the risk that defines the drug, or zongertinib, a HER2-selective tyrosine kinase inhibitor approved by the FDA in 2025 and moved to first line in 2026. NTRK fusion: larotrectinib or entrectinib, tumour-agnostically. NRG1 fusion: zenocutuzumab, which gave a 29 percent response rate in the 93 patients with non-small-cell lung cancer in the eNRGy study and holds FDA accelerated approval from 4 December 2024. None of the HER2, NTRK or NRG1 options has a lung-specific NICE recommendation.

Pembrolizumab alone (KEYNOTE-024), atezolizumab alone (IMpower110: median overall survival 20.2 against 13.1 months in the PD-L1-highest group, hazard ratio 0.59) or cemiplimab alone (EMPOWER-Lung 1), with chemotherapy added where the disease burden is high or a fast response is needed. The threshold matters: CheckMate 026, which used 5 percent, failed outright (progression-free survival hazard ratio 1.15). In England NICE funds pembrolizumab (TA531, stopped at two years), atezolizumab (TA705) and cemiplimab with chemotherapy (TA1165).

Platinum doublet chemotherapy with a checkpoint inhibitor: pemetrexed and platinum with pembrolizumab for non-squamous disease (KEYNOTE-189; NICE TA683) or carboplatin and paclitaxel with pembrolizumab for squamous disease (KEYNOTE-407; NICE TA770). Alternatives are atezolizumab with bevacizumab, carboplatin and paclitaxel (IMpower150; NICE TA584), durvalumab with tremelimumab and chemotherapy (POSEIDON: median overall survival 14.0 against 11.7 months, hazard ratio 0.77) and nivolumab with ipilimumab and two cycles of chemotherapy (CheckMate 9LA: 14.1 against 10.7 months, hazard ratio 0.69), the last of which NICE does not recommend (TA724), so it is not routinely funded in England. Where immunotherapy is contraindicated, chemotherapy alone with maintenance pemetrexed in non-squamous disease.

Docetaxel, with nintedanib in adenocarcinoma after first-line chemotherapy (LUME-Lung 1: median progression-free survival 3.4 against 2.7 months; NICE TA347), or single-agent chemotherapy. Where a checkpoint inhibitor was not given first line, nivolumab (CheckMate 017: median overall survival 9.2 against 6.0 months; CheckMate 057: 12.2 against 9.4 months), atezolizumab (OAK: 13.8 against 9.6 months) or pembrolizumab in PD-L1-positive disease (KEYNOTE-010: 10.4 against 8.5 months at 2 mg/kg, hazard ratio 0.71) each beat docetaxel. Ramucirumab with docetaxel (REVEL: median overall survival 10.5 against 9.1 months) is licensed but not recommended by NICE (TA403). Antibody-drug conjugates are entering this space: datopotamab deruxtecan holds an FDA approval from 2025 for EGFR-mutant disease after a tyrosine kinase inhibitor and platinum chemotherapy, and patritumab deruxtecan and sacituzumab tirumotecan are in phase 3. Re-treatment with a checkpoint inhibitor after progression on one is not supported by evidence.

The two formats that will decide the next five years. Antibody-drug conjugates: datopotamab deruxtecan against TROP2 improved progression-free but not overall survival in TROPION-Lung01 (hazard ratios 0.75 and 0.94) and holds a 2025 FDA approval for EGFR-mutant disease after a tyrosine kinase inhibitor and platinum chemotherapy; patritumab deruxtecan against HER3 improved progression-free survival in HERTHENA-Lung02 (5.8 against 5.4 months, hazard ratio 0.77) without an overall survival gain and its application was withdrawn; telisotuzumab vedotin against c-Met gave a 28.6 percent response rate in LUMINOSITY, 34.6 percent where c-Met expression was high, and was approved by the FDA in 2025; trastuzumab deruxtecan holds the HER2-mutant indication on DESTINY-Lung02. Bispecific antibodies: ivonescimab, which binds PD-1 and VEGF in one molecule, beat pembrolizumab on progression-free survival in HARMONi-2 (hazard ratio 0.51) with a significant overall survival result announced in 2026, and beat chemotherapy after EGFR inhibition in HARMONi-A (7.1 against 4.8 months, hazard ratio 0.46), but its first global trial, HARMONi-3, missed statistical significance for progression-free survival at interim in May 2026; amivantamab, which binds EGFR and MET, is already standard first line with lazertinib; and tarlatamab, which binds DLL3 and CD3, is the first T-cell engager to improve survival in a common solid tumour (DeLLphi-304, overall survival hazard ratio 0.60). None of these regimens is funded in England outside amivantamab with lazertinib, and the pattern to watch is the one TROPION-Lung01 and HERTHENA-Lung02 set: a progression-free survival gain that does not become an overall survival gain.

Four cycles of cisplatin with etoposide and concurrent thoracic radiotherapy starting with cycle 1, then consolidation durvalumab for up to two years and, in most patients, prophylactic cranial irradiation. The radiotherapy schedule is 45 Gy twice daily over three weeks (Intergroup 0096: median survival 23 against 19 months, five-year survival 26 against 16 percent, grade 3 oesophagitis 27 against 11 percent) or 66 Gy once daily, which CONVERT found equivalent. ADRIATIC added durvalumab after chemoradiotherapy and gave median overall survival 55.9 against 33.4 months (hazard ratio 0.73, p=0.01), the largest single gain recorded in this disease; NICE TA1099 funds it in England. Prophylactic cranial irradiation rests on the Auperin meta-analysis of 987 patients (three-year survival 20.7 against 15.3 percent, relative risk of death 0.84), qualified by the Japanese trial of Takahashi, which found no benefit when brain MRI surveillance replaced it.

Four to six cycles of platinum and etoposide with a checkpoint inhibitor, continued as maintenance. IMpower133 added atezolizumab (NICE TA638, performance status 0 or 1 only), CASPIAN added durvalumab (NICE TA1041, same restriction) and ASTRUM-005 added serplulimab (NICE TA1167); adebrelimab and benmelstobart are approved in China. IMforte showed that adding lurbinectedin to atezolizumab maintenance prolongs survival, and the FDA converted lurbinectedin's accelerated approval on it. Consolidation thoracic radiotherapy is offered where thoracic disease remains: CREST missed its one-year endpoint (33 against 28 percent, p=0.066) but tripled two-year survival (13 against 3 percent, p=0.004). Prophylactic cranial irradiation is now a discussion rather than a rule, because MRI surveillance is available.

Whether the relapse is platinum-sensitive (more than 90 days, and often more than 180) decides the first choice. Platinum-sensitive relapse is re-treated with platinum and etoposide. Otherwise: tarlatamab, a DLL3 and CD3 bispecific T-cell engager, gave a 40 percent response rate at 10 mg in DeLLphi-301 and beat chemotherapy in DeLLphi-304, with cytokine release syndrome in about half and a mandatory monitored first dose; lurbinectedin gave a 35.2 percent response rate in its basket cohort; topotecan, oral or intravenous, remains the long-standing option. England is restrictive here: NICE TA1091 does not recommend tarlatamab, lurbinectedin has no United Kingdom marketing authorisation, and TA184 recommends oral topotecan only where re-treatment is inappropriate and CAV is contraindicated.

Where metastases are few, local treatment of all of them alongside systemic therapy. SABR-COMET randomised 99 patients with one to five oligometastatic lesions to stereotactic ablative radiotherapy plus standard care or standard care alone and found longer overall survival, with lung primaries well represented. In oncogene-driven disease, a single progressing site during an otherwise effective targeted drug is treated with radiotherapy or surgery and the drug continued, rather than changing line. The evidence is from small randomised trials and the definition of oligometastatic disease is still argued over.

Breathlessness is treated by cause and by symptom at once: a handheld fan, low-dose oral morphine, a benzodiazepine only where anxiety is prominent, oxygen only where the patient is hypoxic, and a breathlessness service where one exists. A malignant pleural effusion is drained and then either pleurodesed with talc or managed with an indwelling pleural catheter: TIME2 found breathlessness relief identical (24.7 against 24.4 mm on a 100 mm scale, p=0.96) and AMPLE found the catheter reduced total hospital days (10.0 against 12.0, p=0.03), so the choice turns on trapped lung, home support and how much hospital time the patient will accept. An obstructing endobronchial tumour is debulked at rigid bronchoscopy with cryotherapy, argon plasma or laser and held open with an airway stent, then treated with external beam or endobronchial brachytherapy. Superior vena cava obstruction is relieved with an endovascular stent within a day. Early integrated palliative care from diagnosis of incurable disease improves quality of life and mood.

A single 8 Gy fraction of radiotherapy for an uncomplicated painful bone metastasis: the Dutch Bone Metastasis Study found response to initial treatment 71 against 73 percent for a multi-fraction course (p=0.84), and retreatment, needed more often after a single fraction, worked in 63 percent. A bisphosphonate or denosumab reduces skeletal events. Spinal cord compression is treated with dexamethasone, same-day whole-spine MRI and surgery or radiotherapy within 24 hours. For one to four brain metastases, stereotactic radiosurgery alone with MRI surveillance: JROSG 99-1 found adding whole-brain radiotherapy did not lengthen life (7.5 against 8.0 months, p=0.42) though it halved twelve-month brain recurrence (46.8 against 76.4 percent), and QUARTZ found whole-brain radiotherapy added nothing to steroids and supportive care in patients unfit for either. In driver-positive disease, the brain-penetrant drug often controls the metastases without radiotherapy.