PD-L1-high non-small-cell lung cancer without a driver mutation: the decisions you may face
4 treatment settings, 4 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.
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.
Pembrolizumab is a PD-1 blocking antibody approved in more than 40 settings, from melanoma and lung cancer to the first tumour-agnostic approval for mismatch-repair-deficient tumours in 2017, and before and after surgery in triple-negative breast cancer. A subcutaneous form arrived in 2025, and it is the backbone partner for ADCs and personalised neoantigen vaccines.
A PD-1 blocker that is the standard for advanced skin squamous cell carcinoma, and in 2025 became the first adjuvant immunotherapy for it.
A PD-L1 blocker used in lung, liver, and bladder cancer. In 2026 it became the first drug approved based on a blood test showing leftover cancer after bladder surgery.
Nivolumab was the second PD-1 blocker and is often combined with ipilimumab. Long-term data show about half of advanced melanoma patients alive at 10 years on the combination.
Ipilimumab was the first checkpoint inhibitor (2011), and proved the immune system could be unleashed against cancer.
- Tests PembrolizumabFirst-line metastatic NSCLC without EGFR/ALK: pembrolizumab alone (PD-L1 TPS ≥50%, KEYNOTE-024) or pembrolizumab + platinum-pemetrexed (any PD-L1, non-squamous, KEYNOTE-189)
Show survival figures (1)
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.
- 5-year OS 31.9% vs 16.3% (024); 19.4% vs 11.3% (189).
KEYNOTE-024: overall survival at 5 years, PD-L1 ≥50% (%): Pembrolizumab 31.9 (n=154) vs Chemotherapy 16.3 (n=151) · HR 0.62 · source - Tests PembrolizumabUntreated advanced non-small-cell lung cancer without EGFR or ALK alterations and PD-L1 tumour proportion score of 1 percent or more: pembrolizumab versus platinum doublet chemotherapy
Show survival figures (1)
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.
- Median overall survival 20.0 vs 12.2 months (PD-L1 50% or more, hazard ratio 0.69); 16.7 vs 12.1 months (1% or more, hazard ratio 0.81); no difference at 1 to 49%.
Overall survival, PD-L1 tumour proportion score 50% or more (months): Pembrolizumab 20 (n=299) vs Platinum chemotherapy 12.2 (n=300) · HR 0.69 · source - Tests CemiplimabUntreated advanced non-small-cell lung cancer with PD-L1 of 50 percent or more and no EGFR, ALK or ROS1 alteration: cemiplimab versus platinum doublet chemotherapy, with crossover at progression
Show survival figures (1)
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.
- Median overall survival not reached vs 14.2 months (hazard ratio 0.57) in PD-L1 50% or more; 26.1 vs 13.3 months in the three-year update; median progression-free survival 8.2 vs 5.7 months.
Overall survival, PD-L1 50% or more (three-year update) (months): Cemiplimab 26.1 (n=283) vs Platinum chemotherapy 13.3 (n=280) · HR 0.57 · source
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Hypothyroidism (immune-mediated) · Pooled monotherapy data, >2,800 patients | 8% | - |
| Pneumonitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 3.4% | - |
| Colitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 1.7% | - |
| Hepatitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 0.7% | - |
- No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Pneumonitis (immune-mediated) · Monotherapy pooled | 3% | 0.8% |
| Hepatitis (immune-mediated) · Monotherapy pooled | 1.8% | 0.7% |
| Colitis (immune-mediated) · Monotherapy pooled | 1% | 0.5% |
| Hypothyroidism (immune-mediated) · Monotherapy pooled | 4.9% | 0.2% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis with ipilimumab (1+3 mg/kg) · Monotherapy pooled unless stated | 25% | 14.4% |
| Hepatitis with ipilimumab · Monotherapy pooled unless stated | 15% | 13.4% |
| Colitis · Monotherapy pooled unless stated | 2.9% | 1.7% |
| Hepatitis · Monotherapy pooled unless stated | 1.8% | 1.5% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis (with nivolumab 1+3) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 25% | 14.4% |
| Hepatitis (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 15% | 13.4% |
| Rash (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 28% | 4.8% |
| Adrenal insufficiency (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 8% | 2.6% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Between Pembrolizumab, Cemiplimab, Atezolizumab and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in KEYNOTE-024 & KEYNOTE-189 and KEYNOTE-042, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- Which side effects of Pembrolizumab or Atezolizumab are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Non-Small Cell Lung Cancer), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- 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.
Add these to your appointment list, or take the full question set for this cancer.
Advanced, first line, PD-L1 1 to 49 percent
Pembrolizumab plus platinum doublet (KEYNOTE-189, KEYNOTE-407); monotherapy is not recommended below 50 percent.
Pembrolizumab is a PD-1 blocking antibody approved in more than 40 settings, from melanoma and lung cancer to the first tumour-agnostic approval for mismatch-repair-deficient tumours in 2017, and before and after surgery in triple-negative breast cancer. A subcutaneous form arrived in 2025, and it is the backbone partner for ADCs and personalised neoantigen vaccines.
Carboplatin is a platinum chemotherapy that crosslinks DNA; it is part of the standard pre-surgery regimen for triple-negative breast cancer.
Pemetrexed is the chemotherapy that, with a platinum drug, became the first approved treatment for mesothelioma in 2004, and is still the backbone today.
A microtubule poison discovered in the Pacific yew tree, among the most used chemotherapies in breast, lung, and ovarian cancer.
- Tests PembrolizumabFirst-line metastatic NSCLC without EGFR/ALK: pembrolizumab alone (PD-L1 TPS ≥50%, KEYNOTE-024) or pembrolizumab + platinum-pemetrexed (any PD-L1, non-squamous, KEYNOTE-189)
Show survival figures (1)
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.
- 5-year OS 31.9% vs 16.3% (024); 19.4% vs 11.3% (189).
KEYNOTE-024: overall survival at 5 years, PD-L1 ≥50% (%): Pembrolizumab 31.9 (n=154) vs Chemotherapy 16.3 (n=151) · HR 0.62 · source
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Hypothyroidism (immune-mediated) · Pooled monotherapy data, >2,800 patients | 8% | - |
| Pneumonitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 3.4% | - |
| Colitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 1.7% | - |
| Hepatitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 0.7% | - |
- No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Dose by Calvert formula using GFR (see the calculators).
- Not recommended for CrCl below 45.
- Between Pembrolizumab, Carboplatin, Pemetrexed and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in KEYNOTE-024 & KEYNOTE-189, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- Which side effects of Pembrolizumab are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Non-Small Cell Lung Cancer), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- 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.
Add these to your appointment list, or take the full question set for this cancer.
Advanced, after progression on immunotherapy
Platinum doublet if not yet given; docetaxel with or without ramucirumab; clinical trials of antibody-drug conjugates and bispecifics.
The first chemotherapy to extend life in prostate cancer (2004), now part of triplet therapy at first metastatic diagnosis.
An antibody that blocks the VEGF receptor, approved in liver cancer only for patients with a high AFP blood level, the first biomarker-selected HCC drug.
Carboplatin is a platinum chemotherapy that crosslinks DNA; it is part of the standard pre-surgery regimen for triple-negative breast cancer.
Pemetrexed is the chemotherapy that, with a platinum drug, became the first approved treatment for mesothelioma in 2004, and is still the backbone today.
- Previously treated advanced NSCLC: Dato-DXd vs docetaxel
PFS HR 0.75; OS HR 0.94.
Progression-free survival (BICR) (months): Datopotamab deruxtecan 4.4 (n=299) vs Docetaxel 3.7 (n=305) · HR 0.75 · source
- Do not give if bilirubin above ULN, or AST/ALT above 1.5 x ULN with alkaline phosphatase above 2.5 x ULN (treatment-related deaths).
- Dose by Calvert formula using GFR (see the calculators).
- Not recommended for CrCl below 45.
- Between Docetaxel, Ramucirumab, Carboplatin and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in TROPION-Lung01, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Non-Small Cell Lung Cancer), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- 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.
Add these to your appointment list, or take the full question set for this cancer.
Duration and stopping
Two years of immunotherapy for patients in response, with retreatment at relapse; management of immune-related adverse events by organ.
Pembrolizumab is a PD-1 blocking antibody approved in more than 40 settings, from melanoma and lung cancer to the first tumour-agnostic approval for mismatch-repair-deficient tumours in 2017, and before and after surgery in triple-negative breast cancer. A subcutaneous form arrived in 2025, and it is the backbone partner for ADCs and personalised neoantigen vaccines.
Immune checkpoint inhibitors are antibodies against CTLA-4, PD-1 or PD-L1 that release the brakes on T cells so they attack the cancer. They are approved in more than 20 tumour types and produce lasting, sometimes curative responses that chemotherapy rarely does, but most patients do not respond and autoimmune side effects are the cost.
- Durable, sometimes curative responses
- Broad applicability
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Hypothyroidism (immune-mediated) · Pooled monotherapy data, >2,800 patients | 8% | - |
| Pneumonitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 3.4% | - |
| Colitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 1.7% | - |
| Hepatitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 0.7% | - |
- No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Most patients do not respond
- Autoimmune toxicity
- Biomarkers are imperfect
- Between Pembrolizumab and Immune checkpoint inhibitors, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- Which side effects of Pembrolizumab are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Non-Small Cell Lung Cancer), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- 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.
Add these to your appointment list, or take the full question set for this cancer.