Non-Squamous Cell Carcinoma (Non-SCC)
PD-L1 Tumor Proportion Score (TPS) ≥ 50%
1.1. Clinicians are advised to use single-agent pembrolizumab, cemiplimab, or atezolizumab. (HS)
1.2. Pembrolizumab with carboplatin and pemetrexed, or cemiplimab with carboplatin and pemetrexed, may be considered. (MW)
1.3. Atezolizumab with carboplatin and nab-paclitaxel, with or without bevacizumab (if no contraindications), may be offered. (MW)
1.4. Nivolumab with ipilimumab is an option. (MW)
1.5. Nivolumab plus ipilimumab combined with two cycles of platinum-based chemotherapy may be offered. (MW)
1.6. Durvalumab with tremelimumab and platinum-based chemotherapy may also be considered. (MW)
PD-L1 TPS 1–49%
1.7. Pembrolizumab with carboplatin and pemetrexed, or cemiplimab with carboplatin and pemetrexed, should be offered. (MS)
1.8. Atezolizumab with carboplatin and nab-paclitaxel ± bevacizumab (if not contraindicated) may be used. (MW)
1.9. Nivolumab with ipilimumab may be considered. (MW)
2.0. Nivolumab and ipilimumab with two cycles of platinum chemotherapy may be used. (MW)
2.1. Durvalumab and tremelimumab with platinum-based chemotherapy may be offered. (MW)
2.2. If a patient is ineligible for or refuses platinum doublet ± PD-(L)1 inhibitor, monotherapy with anti-PD-1 may be an alternative. (MW)
PD-L1 TPS <1% or Unknown Expression
2.3. Pembrolizumab with carboplatin and pemetrexed, or cemiplimab with carboplatin and pemetrexed, may be offered. (MW)
2.4. Atezolizumab with carboplatin and nab-paclitaxel ± bevacizumab (if not contraindicated) may be considered. (MW)
2.5. Nivolumab and ipilimumab may be used. (MW)
2.6. Nivolumab and ipilimumab with two cycles of platinum-based chemotherapy may be offered. (MW)
2.7. Durvalumab and tremelimumab with platinum chemotherapy may also be considered. (MW)
Squamous Cell Carcinoma (SCC)
PD-L1 TPS ≥ 50%
3.1. Single-agent pembrolizumab, cemiplimab, or atezolizumab should be offered. (HS)
3.2. Pembrolizumab with carboplatin and paclitaxel (or nab-paclitaxel), or cemiplimab with carboplatin and paclitaxel, may be considered. (MW)
3.3. Nivolumab with ipilimumab is a treatment option. (MS)
3.4. Nivolumab and ipilimumab combined with two cycles of platinum-based chemotherapy may be offered. (MW)
3.5. Durvalumab with tremelimumab and platinum-based chemotherapy may also be considered. (MW)
PD-L1 TPS 1–49%
3.6. Pembrolizumab with carboplatin and paclitaxel (or nab-paclitaxel), or cemiplimab with carboplatin and paclitaxel, should be used. (MS)
3.7. Nivolumab and ipilimumab may be considered. (MW)
3.8. Nivolumab and ipilimumab combined with two cycles of platinum chemotherapy may be used. (MW)
3.9. Durvalumab with tremelimumab and platinum-based chemotherapy is another option. (MW)
4.0. If a patient cannot receive or declines platinum doublet ± anti-PD-(L)1, monotherapy with anti-PD-1 may be used. (MW)
PD-L1 TPS <1% or Unknown Expression
4.1. Pembrolizumab with carboplatin and paclitaxel (or nab-paclitaxel), or cemiplimab with carboplatin and paclitaxel, should be considered. (MW)
4.2. Nivolumab and ipilimumab may be offered. (MW)
4.3. Nivolumab and ipilimumab with two cycles of platinum chemotherapy may be considered. (MW)
4.4. Durvalumab with tremelimumab and platinum-based chemotherapy may be used. (MW)
Patients with Unspecified Histology
4.5. Patients with advanced lung cancer should be referred early to palliative care teams offering both inpatient and outpatient support alongside cancer-directed treatment. (HS)
4.6. Patients who are not candidates for immunotherapy and have good performance status should be treated with platinum-based doublet therapy. (HS)
4.7. For those with contraindications to platinum, nonplatinum combination therapies may be considered. (MW)
Patients with Contraindications to Bevacizumab
4.8. Bevacizumab should be avoided in patients with squamous histology, significant hemoptysis, poor organ function, ECOG performance status >1, severe cardiovascular disease, or uncontrolled hypertension. (HS)
4.9. Combining maintenance bevacizumab with pemetrexed offers no survival benefit and adds significant toxicity compared to maintenance with either agent alone. (MW)
Previously Treated with Immune Checkpoint Inhibitors (No Prior Chemotherapy)
5.0. Platinum-based doublet chemotherapy should be offered. (LS)
Previously Treated with Both Chemotherapy and Immunotherapy
5.1. Docetaxel, with or without ramucirumab, should be considered following prior platinum-based chemotherapy. (LS)
5.2. Pemetrexed or gemcitabine may be offered if the patient previously received platinum chemotherapy. (LW)
5.3. Trastuzumab deruxtecan may be used in patients with HER2-overexpressing NSCLC defined as IHC 3+ using gastric scoring criteria. (VLW)