EvidenceNon-small-cell lung cancer

The survival benefit first reported in 2023 has held five years after the last dose of adjuvant osimertinib, which answers the worry that a three-year course only delays relapse. Patients with an exon 19 deletion gained most; the L858R estimate crosses one and is less certain. Nothing here changes the recommendation, which already rests on the 2023 analysis, but it tightens the case for testing every resected non-squamous tumour for EGFR mutations.

For a patient weighing the FLAURA2 regimen against osimertinib alone, the extra toxicity is front-loaded: the hardest months are the four induction cycles, and once pemetrexed stops the profile returns to that of osimertinib by itself. Kidney function deserves watching during pemetrexed maintenance.

Useful for a patient offered adagrasib after chemotherapy or immunotherapy who wants the trial explained without jargon. It adds no new data; the primary KRYSTAL-12 publication and the trial page remain the reference for the numbers.

For the first time a new drug has beaten pembrolizumab, the global first-line standard, in a randomised lung cancer trial, and it did so by combining checkpoint blockade with anti-angiogenesis in one molecule. For patients outside China nothing changes yet: the drug is not approved in the West, the trial was single-country, and survival benefit has not been shown. If confirmed in the global HARMONi-3 and HARMONi-7 trials, PD-1 x VEGF bispecifics could replace PD-1 antibodies as the immunotherapy backbone.

This is the number behind almost every statement about how much cancer there is. It shows the burden shifting towards low- and middle-income countries and towards older populations, which is why prevention, screening and affordable treatment in those settings decide the global trend. OnCo's country and prevalence pages draw on the same GLOBOCAN release.

Patients newly diagnosed with EGFR-mutated advanced lung cancer now have a first-line option that improves survival over osimertinib, particularly if they have high-risk features. The trade-off is intravenous (now subcutaneous) infusions and considerably more skin, nail and clotting toxicity, so osimertinib alone remains reasonable for those who prioritise convenience and tolerability. Both this regimen and osimertinib plus chemotherapy (FLAURA2) are approved; there is no direct comparison.

Patients with KRAS G12C lung cancer that has progressed after chemo-immunotherapy can take an oral KRAS inhibitor instead of docetaxel and gain a somewhat longer time to progression with fewer severe side effects, but should understand that most tumours become resistant within a year and that survival is not improved. KRAS G12C testing is worthwhile, but first-generation inhibitors are a step rather than a cure; combinations and next-generation inhibitors are the active research fronts.

Relapse after surgery is driven by particular subclones that can be identified in the primary tumour and tracked in blood, which argues for evolution-aware adjuvant strategies. The pollution finding reframes carcinogenesis: some agents promote already-mutant cells rather than causing mutations.

Patients with operable stage II-III lung cancer without EGFR or ALK alterations should have chemo-immunotherapy discussed before surgery rather than only afterwards. Three pre-operative cycles do not compromise the operation and improve cure rates. Whether to continue immunotherapy after surgery, as the perioperative trials do, and whether patients with pCR need any further treatment, remain open questions.

This edition documented the treatment-driven fall in lung cancer deaths that followed targeted therapy and immunotherapy, a rare case of new drugs visibly moving national mortality statistics.

Checkpoint inhibitors are now given to hundreds of thousands of patients a year, many in community clinics and emergency departments, so a common, explicit playbook for their autoimmune side effects saves lives. The guideline standardised when to stop, when to give steroids and when to escalate, and made multidisciplinary toxicity teams routine. It does not remove the judgement needed for rare events or for patients whose cancer is responding.

This report marked the shift of the global cancer burden towards breast cancer and towards lower-income countries, and it is the baseline most 2020s policy documents cite. The GLOBOCAN 2022 release has since updated the totals.

Every resected non-squamous lung cancer should be tested for EGFR mutations, because patients who carry one live longer if they take osimertinib for three years after surgery. The trial does not tell us whether adjuvant chemotherapy can be omitted, nor what happens on relapse after osimertinib, and the three-year duration was chosen empirically.

India's cancer problem is a late-diagnosis problem as much as a treatment problem: the same cancers that dominate (oral, cervical, breast) are the ones screening and vaccination can prevent or catch early. The numbers set the priorities of the National Cancer Grid, PM-JAY oncology packages and the national screening programme.

For ALK-positive advanced lung cancer, lorlatinib as the first drug offers the possibility of many years without progression and strong protection against brain metastases. Alectinib and brigatinib remain alternatives with a gentler side-effect profile; the choice weighs lorlatinib's cognitive, metabolic and weight effects against its unmatched duration of control.

Lung screening works when it uses volumetric nodule management, and it works against a no-screening control. The protocol underpins the UK Targeted Lung Health Check programme and European recommendations. Benefit in women remains less precisely estimated.

CONCORD is the evidence base for national cancer plans and for the statement that where you live changes your chance of surviving cancer. Its country tables are the benchmark health systems use to judge early diagnosis and treatment access.

This was the most cited description of the global cancer burden until the 2020 release and is the reference behind many national cancer plans of the late 2010s. Its country-level comparisons showed where prevention, such as HPV and hepatitis B vaccination and tobacco control, would have the largest effect.

Anyone diagnosed with advanced lung cancer should have EGFR testing before treatment, because osimertinib as the first drug gives the longest disease control, protects the brain, and is well tolerated. Chemotherapy is not the first step for these patients. The remaining questions are whether to intensify upfront (adding chemotherapy or amivantamab) and how to treat resistance when it develops.

This is the separate paper behind the survival figure quoted for dacomitinib. It is a real but modest gain, and the US label notes that overall survival was not formally tested because the response rate comparison earlier in the testing order was not significant, so the P value is descriptive.

Most patients with newly diagnosed advanced non-squamous lung cancer that lacks a targetable mutation should receive chemotherapy plus pembrolizumab; those with PD-L1 of 50% or more may reasonably receive pembrolizumab alone. About one in five patients is alive at five years, compared with roughly one in ten with chemotherapy alone. Patients with EGFR or ALK alterations were excluded and should have targeted therapy first.

Complementary approaches used alongside treatment are one thing; substituting an alternative therapy for surgery, chemotherapy, radiotherapy or hormone therapy in a curable cancer is associated with a large increase in the risk of dying. The finding is the evidence base for offering complementary therapies inside cancer centres and for asking every patient, without judgement, what else they are using.

This is the trial behind brigatinib's first approval, after crizotinib, and it set the 180 mg dose with a 90 mg lead-in that the label uses. For a patient it shows a drug with strong activity in the brain and an unusual early lung side effect that the lead-in week was designed to soften.

ARCHER 1050 supported dacomitinib's 2018 US first-line approval and was the first head-to-head win of a second-generation EGFR inhibitor over a first-generation one on progression-free survival. FLAURA, reported the same year, made osimertinib the usual first choice, so dacomitinib is now rarely used.

ASCEND-4 gave ceritinib its 2017 US first-line approval and showed that a second-generation ALK inhibitor beats chemotherapy in untreated disease. In practice alectinib, brigatinib and lorlatinib, tested against crizotinib rather than chemotherapy, became the usual first-line choices, partly because ceritinib's gut side effects at 750 mg fasted were hard to live with.

GBD is the other major global cancer count alongside GLOBOCAN, using different methods, and its burden measures in years of life lost make the case that cancer control is largely a problem of ageing populations in middle-income countries.

Patients with stage III lung cancer that cannot be removed surgically should receive a year of durvalumab after completing chemoradiotherapy, provided they have not progressed. This roughly doubles the chance of being alive without progression at five years. Whether the benefit extends to PD-L1-negative tumours is contested, and the EGFR-mutated subgroup is better served by osimertinib (LAURA).

Lung cancers keep evolving after they form, and it is ongoing chromosomal instability rather than the number of mutations that best predicts who will relapse. This gives a rationale for targeting the earliest (clonal) drivers and neoantigens and for tracking evolution in blood after surgery.

China accounts for roughly a quarter of the world's cancer cases, and this paper is the reference that made its burden legible internationally. It explains why Chinese trial programmes and drug pipelines concentrate on lung, stomach, oesophageal and liver cancers.

Alongside the CheckMate trials this study replaced docetaxel with PD-1 blockade as second-line treatment for most lung cancers, and its PD-L1 threshold of 1% became the basis of pembrolizumab's label in previously treated disease.

This trial is why PD-L1 is measured on every new advanced lung cancer and why a patient with a high score can start immunotherapy without chemotherapy. Together with KEYNOTE-189 for the rest of the population, it moved checkpoint inhibitors from second-line rescue to the first treatment most lung cancer patients receive.

With CheckMate 057 this trial ended docetaxel's role as the default second-line treatment in lung cancer and gave the first phase 3 proof that PD-1 blockade extends life in a common carcinoma. Its PD-L1-independent benefit in squamous disease still shapes how the biomarker is used.

With CheckMate 017 in squamous disease, this trial ended docetaxel's reign as the default second-line treatment for lung cancer and established PD-1 blockade as standard after chemotherapy. Its PD-L1 finding shaped how later first-line trials were designed and how the biomarker is used in the clinic.

This trial gave lung cancer its immunotherapy biomarker. The 50% PD-L1 cut-off decides today whether a patient with advanced lung cancer can start immunotherapy alone or needs chemotherapy added, and the five-year follow-up later showed long-term survivors among first-line responders.

This paper turned a hypothesis into a biomarker: tumour mutational burden is now measured by commercial panels and underpins the tissue-agnostic approval of pembrolizumab for TMB-high tumours. It also explains why smokers' lung cancers, long the hardest to treat, respond better to immunotherapy than never-smokers' cancers.

One of the most cited descriptions of the global cancer burden of the 2010s, it framed the shift of cancer towards lower-income countries that later GLOBOCAN releases have confirmed.

The most frequently mutated oncogene in cancer stopped being undruggable, and patients with KRAS G12C lung and bowel cancers now have targeted pills. The approach, exploiting a mutation-created chemical handle and an inactive-state pocket, has become a template for other hard targets.

This study is why PD-1 inhibitors were developed across cancers rather than in melanoma alone: unexpected activity in lung cancer, historically thought immune-resistant, changed drug development priorities industry-wide. It also introduced PD-L1 immunohistochemistry as a candidate biomarker and pneumonitis as a signature toxicity. Within five years PD-1 blockade was approved in more than ten cancers.

For years the most cited paper in oncology, it fixed the picture of cancer as a growing problem of developing countries and is the baseline against which the 2012, 2018, 2020 and 2022 GLOBOCAN releases show the burden rising.

For people with a heavy smoking history, an annual low-dose CT scan is one of the few screening tests proven to reduce cancer deaths. Most abnormal scans are not cancer, so screening must be paired with careful nodule management. It does not apply to never-smokers or light smokers.

Palliative care is not what happens when treatment stops; it works best alongside cancer treatment from the start. Patients feel better, are less depressed and may live longer. Access remains the constraint: most of the world's patients never see a palliative care specialist.

The first of the modern GLOBOCAN summaries in CA, it set the template that Jemal, Torre, Bray and Sung later followed and provides the 2002 baseline for tracking how the global burden has grown and shifted.

Smoking is the single largest preventable cause of cancer death, and quitting at any age helps, with the greatest gain from quitting young. Cessation support belongs in every cancer service, including lung screening programmes.

The QLQ-C30 made patient-reported quality of life a standard trial endpoint and is the instrument behind many of the quality of life claims on drug labels and in health technology assessments. Cancer-specific modules were later added on top of the core questionnaire.

This paper is why TP53 status is reported in almost every tumour genome and why mutational signatures can point to causes. Its idea that mutation patterns record exposures grew into the mutational signature field, and TP53 mutation remains a marker of poor prognosis and a drug target still being pursued.

Doll and Hill's 1950 study is where the evidence that smoking causes cancer begins. Everything from cigarette warnings and tax to smoke-free laws and lung screening eligibility descends from this study and the cohort that followed it.