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Lung cancers that carry a lot of PD-L1 and no targetable mutation can be treated with an immunotherapy antibody alone instead of chemotherapy. Pembrolizumab keeps about a third of patients alive at five years, roughly double what chemotherapy achieved, and adding chemotherapy is reserved for those who need a fast response.
PD-L1 on tumour cells switches off the T cells that would attack them, and the level of expression, measured by immunohistochemistry as the tumour proportion score, was the first biomarker for checkpoint inhibitors in lung cancer. KEYNOTE-024 (2016) randomised 305 patients with untreated advanced non-small-cell lung cancer, PD-L1 of 50 percent or more and no EGFR or ALK alteration to pembrolizumab or platinum chemotherapy: progression-free survival was 10.3 versus 6.0 months, median overall survival 26.3 versus 13.4 months, and 31.9 percent of pembrolizumab patients were alive at five years against 16.3 percent, despite most of the chemotherapy arm crossing over. The FDA approved first-line pembrolizumab monotherapy in October 2016, the first time a checkpoint inhibitor replaced chemotherapy first line in a common cancer.
KEYNOTE-042 (2019) extended monotherapy to PD-L1 of 1 percent or more but showed the gain came from the high expressers; IMpower110 (atezolizumab, 2020) and EMPOWER-Lung 1 (cemiplimab, 2021) reproduced the result with other PD-1 and PD-L1 antibodies, and nivolumab plus ipilimumab (CheckMate 227) offered a chemotherapy-free doublet. For patients with bulky or symptomatic disease pembrolizumab plus platinum doublet (KEYNOTE-189 for non-squamous, KEYNOTE-407 for squamous) gives higher response rates and is the alternative, with no randomised evidence that it prolongs survival over monotherapy in this group. Squamous and non-squamous tumours are treated alike when PD-L1 is high, apart from the chemotherapy partner.
The next generation is trying to beat pembrolizumab directly. Ivonescimab, a PD-1 and VEGF bispecific antibody, beat pembrolizumab on progression-free survival in PD-L1-positive patients in the Chinese HARMONi-2 trial (11.1 versus 5.8 months, hazard ratio 0.51), and HARMONi-3 is the global confirmation with chemotherapy; TROP2 antibody-drug conjugates with pembrolizumab (TROPION-Lung08) and TIGIT antibodies have been tested with mixed results. Open questions are who can stop immunotherapy after two years, how to treat the half of patients who progress within a year, and whether PD-L1 will be replaced by better predictors.
Averages across everyone diagnosed, often years ago. A median is the middle of a group: half the people counted lived longer than the figure shown, and some lived far longer. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
About a quarter to a third of advanced non-small-cell lung cancers express PD-L1 on 50 percent or more of tumour cells, and most of these lack an EGFR, ALK or other targetable driver; they occur mainly in current or former smokers with adenocarcinoma or squamous histology.
Central tumours arise in the large airways, peripheral ones in the alveoli; both drain to hilar then mediastinal nodes, and the pleural lining is a separate cancer site.
Same organ: Mediastinal germ cell tumour, Pleuropulmonary blastoma (types I, Ir, II and III), Type A and type AB thymoma, Type B1 and type B2 thymoma, Type B3 thymoma, Micronodular thymoma with lymphoid stroma, Adenocarcinoma of the lung, Squamous cell carcinoma of the lung, Large cell carcinoma of the lung, Sarcomatoid carcinoma of the lung, Adenosquamous carcinoma of the lung, Invasive mucinous adenocarcinoma of the lung, Adenocarcinoma in situ and minimally invasive adenocarcinoma of the lung, Basaloid squamous cell carcinoma of the lung, Lymphoepithelial carcinoma of the lung, Pulmonary blastoma (adult), Non-small-cell lung cancer, Lung cancer (all types), Small-cell lung cancer, Mesothelioma, Pleural mesothelioma, Thymoma and thymic carcinoma, Childhood lung and airway tumours (pleuropulmonary blastoma, tracheobronchial tumours), Inflammatory myofibroblastic tumour (IMT), EGFR-mutated non-small-cell lung cancer, ALK-positive non-small-cell lung cancer, KRAS G12C-mutant non-small-cell lung cancer, ROS1-positive non-small-cell lung cancer, MET exon 14 and MET-amplified non-small-cell lung cancer, RET fusion-positive non-small-cell lung cancer, BRAF V600E-mutant non-small-cell lung cancer, HER2-mutant non-small-cell lung cancer, NTRK fusion-positive non-small-cell lung cancer, Resectable stage I to III non-small-cell lung cancer, Unresectable stage III non-small-cell lung cancer, Limited-stage small-cell lung cancer, Extensive-stage small-cell lung cancer, Lung neuroendocrine tumours (typical and atypical carcinoid), Large cell neuroendocrine carcinoma of the lung, Thymoma (WHO types A, AB, B1, B2 and B3), Thymic carcinoma
Pembrolizumab alone (KEYNOTE-024, KEYNOTE-042), cemiplimab alone (EMPOWER-Lung 1) or atezolizumab alone; pembrolizumab plus platinum doublet for bulky or symptomatic disease; nivolumab plus ipilimumab as a chemotherapy-free alternative.
Pembrolizumab plus platinum doublet (KEYNOTE-189, KEYNOTE-407); monotherapy is not recommended below 50 percent.
Platinum doublet if not yet given; docetaxel with or without ramucirumab; clinical trials of antibody-drug conjugates and bispecifics.
Two years of immunotherapy for patients in response, with retreatment at relapse; management of immune-related adverse events by organ.
Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year.
The targets of this cancer's medicines and the ones linked to it directly.
Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Sudden severe abdominal pain, a hard or very tender abdomen, or abdominal pain with vomiting and fever. Boxed warning for gastrointestinal perforation on bevacizumab.
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Dose by Calvert formula using GFR (see the calculators).
Not recommended for CrCl below 45.
See all on the product pages:AtezolizumabCarboplatinCemiplimabDocetaxelIpilimumabNivolumabPaclitaxel / nab-paclitaxelPembrolizumabPemetrexedRamucirumab·Printable cards in the navigator
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Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record.
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