cancersCancer

PD-L1-high non-small-cell lung cancer without a driver mutation

aka PD-L1 50 percent or more NSCLC, PD-L1-high lung cancer, Driver-negative PD-L1-high non-small-cell lung cancer, Immunotherapy-eligible lung cancer

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.

Part ofNon-small-cell lung cancer

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.

State of the art

Three antibodies (pembrolizumab, cemiplimab, atezolizumab) approved as monotherapy in PD-L1-high disease.
Two-year fixed duration with retreatment at relapse.

Show survival figures (2)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

Pembrolizumab alone: five-year survival 31.9 percent versus 16.3 percent with chemotherapy in KEYNOTE-024.
Ivonescimab beat pembrolizumab on progression-free survival in HARMONi-2; global confirmation awaited.

Red cards

From the labels and guidelines behind the standard of care. Your team's thresholds win.

Emergency services now
Hypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Atezolizumab Cemiplimab Ipilimumab Nivolumab Pembrolizumab source
Emergency services now
Bleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
Carboplatin Docetaxel Paclitaxel / nab-paclitaxel Pemetrexed source
Emergency services now
Bowel perforation
Sudden severe abdominal pain, a hard or very tender abdomen, or abdominal pain with vomiting and fever. Boxed warning for gastrointestinal perforation on bevacizumab.
Ramucirumab source
Check before combining
Food and drink: Pembrolizumab
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Pembrolizumab source
Check before combining
Kidneys: Carboplatin
Dose by Calvert formula using GFR (see the calculators).
Carboplatin source
Check before combining
Kidneys: Pemetrexed
Not recommended for CrCl below 45.
Pemetrexed source

See all on the product pages:Atezolizumab Carboplatin Cemiplimab Docetaxel Ipilimumab Nivolumab Paclitaxel / nab-paclitaxel Pembrolizumab Pemetrexed Ramucirumab·Printable cards in the navigator

Anatomy and lymph node drainage

Lungs, pleura and mediastinum: subsites and node stations · wireframe schematic, not to scale

Organ atlas →

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.

Subsites

Central airways (squamous, small-cell)PD-L1-high squamous cell carcinoma (monotherapy or with carboplatin-paclitaxel)
Periphery (adenocarcinoma)PD-L1-high adenocarcinoma without a driver (pembrolizumab, cemiplimab or atezolizumab alone, or with platinum-pemetrexed) · PD-L1-high squamous cell carcinoma (monotherapy or with carboplatin-paclitaxel) · PD-L1-high disease with STK11 or KEAP1 co-mutation (poorer immunotherapy response) · PD-L1-high disease with bulky or symptomatic tumour (chemoimmunotherapy for a faster response)
Apex (Pancoast)
Pleura (mesothelioma)
Thymus (anterior mediastinum)PD-L1-high adenocarcinoma without a driver (pembrolizumab, cemiplimab or atezolizumab alone, or with platinum-pemetrexed) · PD-L1-high squamous cell carcinoma (monotherapy or with carboplatin-paclitaxel)

Regional lymph nodes

hilar (N1)
mediastinal (N2)
supraclavicular (N3)

Who gets it and what has changed

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.

Group

lung

Cases by country

Cases by country · GLOBOCAN 2022

All countries →

No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.

Standard of care

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Lines of therapy by subgroup →Staging and risk scores →

Decisions you may face

4 with more than one option · full decision page →

One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.

Advanced, first line, PD-L1 50 percent or more5 Advanced, first line, PD-L1 1 to 49 percent4 Advanced, after progression on immunotherapy4 Duration and stopping2

Advanced, first line, PD-L1 50 percent or more

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.

NCCN Guidelines: Non-Small Cell Lung Cancer

PembrolizumabKEYNOTE-024 & KEYNOTE-189 KEYNOTE-042CemiplimabEMPOWER-Lung 1AtezolizumabNivolumabIpilimumabTumour proportion score (TPS)PD-L1 expression testing (22C3, SP142, SP263)

Advanced, first line, PD-L1 1 to 49 percent

Pembrolizumab plus platinum doublet (KEYNOTE-189, KEYNOTE-407); monotherapy is not recommended below 50 percent.

NCCN Guidelines: Non-Small Cell Lung Cancer

PembrolizumabKEYNOTE-024 & KEYNOTE-189CarboplatinPemetrexedPaclitaxel / nab-paclitaxelPD-1 blockade + chemotherapy in PD-L1-low NSCLC

Advanced, after progression on immunotherapy

Platinum doublet if not yet given; docetaxel with or without ramucirumab; clinical trials of antibody-drug conjugates and bispecifics.

NCCN Guidelines: Non-Small Cell Lung Cancer

DocetaxelRamucirumabCarboplatinPemetrexedTROPION-Lung01

Duration and stopping

Two years of immunotherapy for patients in response, with retreatment at relapse; management of immune-related adverse events by organ.

NCCN Guidelines: Non-Small Cell Lung Cancer

PembrolizumabImmune checkpoint inhibitors Immuno-oncology (IO) and checkpoint blockade

Subtypes & biomarkers

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Subtypes

PD-L1-high adenocarcinoma without a driver (pembrolizumab, cemiplimab or atezolizumab alone, or with platinum-pemetrexed)
PD-L1-high squamous cell carcinoma (monotherapy or with carboplatin-paclitaxel)
PD-L1-high disease with STK11 or KEAP1 co-mutation (poorer immunotherapy response)
PD-L1-high disease with bulky or symptomatic tumour (chemoimmunotherapy for a faster response)

Biomarkers clinicians test

PD-L1 tumour proportion score by immunohistochemistry (22C3, SP263, SP142) on tissue
Absence of EGFR, ALK, ROS1, RET, BRAF, MET, HER2, KRAS G12C and NTRK alterations on a broad panel
STK11 and KEAP1 co-mutations (prognostic)
Tumour mutational burden (of limited use)
Thyroid function, liver enzymes, cortisol and glucose for immune-related adverse events

How often this target appears

History

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2015KEYNOTE-001: PD-L1 expression predicts pembrolizumab response in lung cancer
PembrolizumabKEYNOTE-001 (Garon 2015): pembrolizumab in non-small-cell lung cancer and the 50% PD-L1 cut-off Tumour proportion score (TPS)
2016KEYNOTE-024: pembrolizumab alone beats chemotherapy in PD-L1-high disease; first-line approval
KEYNOTE-024 & KEYNOTE-189PembrolizumabMartin Reck KEYNOTE-024: pembrolizumab alone beats chemotherapy in PD-L1-high lung cancer
2018KEYNOTE-189 and KEYNOTE-407: pembrolizumab plus chemotherapy for all PD-L1 levels
KEYNOTE-024 & KEYNOTE-189PembrolizumabKEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutation
2019KEYNOTE-042: monotherapy label widened to PD-L1 of 1 percent or more, benefit concentrated at 50 percent or more
KEYNOTE-042PembrolizumabTony S. K. Mok
2021EMPOWER-Lung 1: cemiplimab approved in PD-L1-high disease
EMPOWER-Lung 1Cemiplimab
2024HARMONi-2: ivonescimab beats pembrolizumab on progression-free survival in China
HARMONi-2IvonescimabHARMONi-2: ivonescimab, a PD-1 x VEGF bispecific, beats pembrolizumab head-to-head in PD-L1-positive lung cancer Akeso

What changed

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Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.

All 14 changes by month →

FollowWatch this cancer and Saved shows what changed since you last looked.Follow by feed

In development

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What is in development for PD-L1-high non-small-cell lung cancer without a driver mutation, drawn from the whole corpus: 11 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.

Trials under way · 2

Study of Dato-DXd Plus Pembrolizumab vs Pembrolizumab Alone in the First-line Treatment of Subjects With Advanced or Metastatic NSCLC Without Actionab · phase 3 · Daiichi Sankyo
Zimberelimab and Domvanalimab in Combination With Chemotherapy Versus Pembrolizumab With Chemotherapy in Patients With Untreated Metastatic Non-Small Cell Lung Cancer · phase 3 · Gilead Sciences

Trials reported · 7

HARMONi-3 · phase 3 · 2026 · mixed
TROPION-Lung01 · phase 3 · 2023 · mixed
EMPOWER-Lung 1 · phase 3 · 2021 · positive
HARMONi-2 · phase 3 · 2024 · positive
KEYNOTE-024 & KEYNOTE-189 · phase 3 · 2016 · positive
KEYNOTE-042 · phase 3 · 2019 · positive
Lung-MAP S1800A: ramucirumab plus pembrolizumab · phase 2 · 2022 · positive

Combinations being explored · 1

PD-1 blockade + chemotherapy in PD-L1-low NSCLC

Ideas not yet in a trial · 1

Use a blood test at six weeks to decide whether to keep going

Open problems and what is being done

Half of PD-L1-high patients progress within a year and have no predictor to identify them in advance.
Whether adding chemotherapy to a checkpoint inhibitor prolongs survival in PD-L1-high disease has never been tested in a randomised trial.
The two-year stopping rule rests on trial design rather than evidence, and the safe minimum duration is unknown.
Ivonescimab's advantage over pembrolizumab has been shown only in China and only on progression-free survival so far.

Trials

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Trials recruiting now

Recruiting trials near you · live from ClinicalTrials.gov

PD-L1-high non-small-cell lung cancer without a driver mutation

condition: PD-L1-high non-small-cell lung cancer without a driver mutation

Open on ClinicalTrials.gov →

within

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Landmark trials

EMPOWER-Lung 1 HARMONi-2 HARMONi-3 KEYNOTE-024 & KEYNOTE-189 KEYNOTE-042 Lung-MAP S1800A: ramucirumab plus pembrolizumab Study of Dato-DXd Plus Pembrolizumab vs Pembrolizumab Alone in the First-line Treatment of Subjects With Advanced or Metastatic NSCLC Without Actionab TROPION-Lung01 Zimberelimab and Domvanalimab in Combination With Chemotherapy Versus Pembrolizumab With Chemotherapy in Patients With Untreated Metastatic Non-Small Cell Lung Cancer

Expert centres

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Where the expertise is

Expert centres

69 centres in 20 countries · 2 with a trial for this cancer on record · second-opinion finder →

Choose a region from the globe in the header to mark centres near you.

69 centres


Gustave Roussy Villejuif · cancer center	France	none recorded	0	1,855	31,182	ZAP-X gyroscopic radiosurgery Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)	#6
Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center Baltimore · cancer center	United States	NCI comprehensive	0	2,955	41,449	Multi-cancer early detection (MCED)Liquid biopsy (ctDNA)Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems +2	#10
National Cancer Center Hospital Tokyo · government	Japan	none recorded	0	1,599	21,937	none recorded	#13
Netherlands Cancer Institute (NKI-AvL) Amsterdam · cancer center	Netherlands	none recorded	0	1,451	25,873	TIL therapy Immune checkpoint inhibitors MR-guided adaptive radiotherapy	#45
Cancer Hospital, Chinese Academy of Medical Sciences Beijing · cancer center	China	none recorded	0	371	4,070	none recorded	#50
National Cancer Institute (NIH) Bethesda, MD · government	United States	none recorded	1	2,905	47,715	TIL therapy TCR-T cell therapy	-
SWOG Cancer Research Network Portland, OR · consortium	United States	none recorded	1	42	1,880	none recorded	-
Tongji Hospital, Huazhong University of Science and Technology Wuhan · hospital	China	none recorded	0	2,478	31,527	HPV & HBV vaccination Patient-derived organoids Immune checkpoint inhibitors CAR-T cell therapy	-
Peking University Cancer Hospital Beijing · cancer center	China	none recorded	0	1,344	18,195	CAR-T cell therapy Immune checkpoint inhibitors Antibody-drug conjugate (ADC)	-
Leiden University Medical Center Leiden · university	Netherlands	none recorded	0	1,245	16,125	Off-the-shelf cancer vaccines HPV & HBV vaccination Immune checkpoint inhibitors Proton therapy	-
Zhejiang Cancer Hospital Hangzhou · cancer center	China	none recorded	0	1,219	17,635	IMRT / IGRT (modern external beam)Proton therapy Immune checkpoint inhibitors	-
Centre Léon Bérard Lyon · cancer center	France	none recorded	0	1,071	14,301	Comprehensive genomic profiling Small-molecule kinase inhibitors Immune checkpoint inhibitors	-
IRCCS Humanitas Research Hospital Rozzano (Milan) · hospital	Italy	none recorded	0	1,031	10,720	SBRT / SABR (stereotactic radiotherapy)Immune checkpoint inhibitors CAR-NK & CAR-macrophage IMRT / IGRT (modern external beam)	-
Henan Cancer Hospital Zhengzhou · cancer center	China	none recorded	0	970	12,409	Immune checkpoint inhibitors CAR-T cell therapy	-
Istituto Oncologico Veneto IRCCS Padua · cancer center	Italy	none recorded	0	962	12,326	Monoclonal antibodies Immune checkpoint inhibitors CDK4/6 inhibitors	-

(showing the first 15)

These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with PD-L1-high non-small-cell lung cancer without a driver mutation but is thinly recorded here will look small.

Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost. The second-opinion finder explains how referral works in your country.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about PD-L1-high non-small-cell lung cancer without a driver mutation

Generated from this cancer's standard of care, biomarkers, and pipeline · 20 questions

Newly diagnosed

What is my exact diagnosis, stage, and grade, and which tests established them?
Why: Everything else follows from an accurate stage and subtype.
Which biomarkers have been tested on my tumour (for example PD-L1 tumour proportion score by immunohistochemistryon tissue, Absence of EGFR, ALK, ROS1, RET, BRAF, MET, HER2, KRAS G12C and NTRK alterations on a broad panel, STK11 and KEAP1 co-mutations, Tumour mutational burden, Thyroid function, liver enzymes, cortisol and glucose for immune-related adverse events), and what were the results?
Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
Which subtype is my cancer, and does that change the recommended treatment?
Why: Recognised subtypes for this cancer include PD-L1-high adenocarcinoma without a driver, PD-L1-high squamous cell carcinoma, PD-L1-high disease with STK11 or KEAP1 co-mutation.
Is germline (inherited) genetic testing recommended for me or my family?
Why: Inherited variants can change treatment and matter for relatives.

Advanced, first line, PD-L1 50 percent or more

For my situation (advanced, first line, pd-l1 50 percent or more), which of the standard options do you recommend and why?
Why: Guideline options include: 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.
Am I a candidate for Pembrolizumab, Cemiplimab, Atezolizumab or related drugs, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of KEYNOTE-024 & KEYNOTE-189 and KEYNOTE-042 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Advanced, first line, PD-L1 1 to 49 percent

For my situation (advanced, first line, pd-l1 1 to 49 percent), which of the standard options do you recommend and why?
Why: Guideline options include: Pembrolizumab plus platinum doublet (KEYNOTE-189, KEYNOTE-407); monotherapy is not recommended below 50 percent.
Am I a candidate for Pembrolizumab, Carboplatin, Pemetrexed or related drugs, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of KEYNOTE-024 & KEYNOTE-189 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Advanced, after progression on immunotherapy

For my situation (advanced, after progression on immunotherapy), which of the standard options do you recommend and why?
Why: Guideline options include: Platinum doublet if not yet given; docetaxel with or without ramucirumab; clinical trials of antibody-drug conjugates and bispecifics.
Am I a candidate for Docetaxel, Ramucirumab, Carboplatin or related drugs, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of TROPION-Lung01 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Duration and stopping

For my situation (duration and stopping), which of the standard options do you recommend and why?
Why: Guideline options include: Two years of immunotherapy for patients in response, with retreatment at relapse; management of immune-related adverse events by organ.
Am I a candidate for Pembrolizumab, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Any stage

Are there clinical trials I could join, for example of HARMONi-3, Ivonescimab, Study of Dato-DXd Plus Pembrolizumab vs Pembrolizumab Alone in the First-line Treatment of Subjects With Advanced or Metastatic NSCLC Without Actionab, TROPION-Lung01?
Why: Trials are how the next standard of care is set; asking early keeps options open.
Would a second opinion at a high-volume centre change anything, and can you help arrange it?
Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?
Why: Supportive care improves quality of life and helps patients complete treatment.
I read that “Half of PD-L1-high patients progress within a year and have no predictor to identify them in advance”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.
I read that “Whether adding chemotherapy to a checkpoint inhibitor prolongs survival in PD-L1-high disease has never been tested in a randomised trial”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.

Newly diagnosed? Read the first 60 days with PD-L1-high non-small-cell lung cancer without a driver mutation, then print the one-page appointment sheet with room for the answers.

Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.

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Direct links plus the targets, companies, and technologies of this cancer's products.

trials

pairings

PD-1 blockade + chemotherapy in PD-L1-low NSCLC

ideas

Use a blood test at six weeks to decide whether to keep going

people

Julie R. Brahmer Martin Reck Roy S. Herbst Solange Peters Tony S. K. Mok

key papers

HARMONi-2: ivonescimab, a PD-1 x VEGF bispecific, beats pembrolizumab head-to-head in PD-L1-positive lung cancer KEYNOTE-001 (Garon 2015): pembrolizumab in non-small-cell lung cancer and the 50% PD-L1 cut-off KEYNOTE-024: pembrolizumab alone beats chemotherapy in PD-L1-high lung cancer KEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutation

Key papers

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rctThe Lancet 2025

HARMONi-2: ivonescimab, a PD-1 x VEGF bispecific, beats pembrolizumab head-to-head in PD-L1-positive lung cancer

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.

rctNew England Journal of Medicine 2018changed practice

KEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutation

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.

rctNew England Journal of Medicine 2016changed practice

KEYNOTE-024: pembrolizumab alone beats chemotherapy in PD-L1-high lung cancer

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.

translationalNew England Journal of Medicine 2015changed practice

KEYNOTE-001 (Garon 2015): pembrolizumab in non-small-cell lung cancer and the 50% PD-L1 cut-off

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.