The American Society of Clinical Oncology (ASCO) recently released an update to their living guideline, Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations. In this 2026 update, ASCO updated the guideline based on its systematic review process, which included a review of randomized controlled trials spanning March through October of 2025.
The 2026 guideline update, similar to the previous versions, is largely divided into two main sections: non-squamous cell carcinoma and squamous cell carcinoma. Today, we are comparing the latest update to the 2025.1 version, published in July of 2025.
Key Elements of the 2026 ASCO NSCLC Without Driver Alterations Update:
Biomarker Testing
A new recommendation regarding molecular testing was added, recommendation 1.0.
Nonsquamous Cell Carcinoma
Recommendation 1.2, for PD-L1 expression, TPS ≥50%, in the 2025 version is now split into two individual recommendations: Pembrolizumab + carboplatin + pemetrexed; Cemiplimab + carboplatin + pemetrexed.
Similarly, recommendation 1.7 in the 2025 version, for PD-L1 expression, TPS 1%-49%, is now split into two individual recommendations: Pembrolizumab + carboplatin + pemetrexed; Cemiplimab + carboplatin + pemetrexed.
Also, in the PD-L1 expression, TPS 1%-49% section, for patients who are ineligible for or decline combination therapy, the updated recommendation states that Pembrolizumab monotherapy may be offered to these patients.
Another recommendation split in the 2026 update was the 2.3, which is now 1.15 Pembrolizumab + carboplatin + pemetrexed; and Cemiplimab + carboplatin + pemetrexed, both included in the Unknown or Negative PD-L1 Expression, TPS <1% section.
Squamous Cell Carcinoma
Under PD-L1 Expression, TPS 1%-49%, Recommendation 3.6 was split into two recommendations in the 2026 update: Pembrolizumab + carboplatin + paclitaxel (or nab-paclitaxel); Cemiplimab + carboplatin + paclitaxel.
Recommendation 4.1, under Unknown or Negative PD-L1 Expression, TPS <1%, was also split in the 2026 update: Pembrolizumab + carboplatin + paclitaxel (or nab-paclitaxel); Cemiplimab + carboplatin + paclitaxel.
Patients Previously Treated with Chemotherapy and Immune Checkpoint Therapy
In the 2026 update, recommendation 4.3 received an update: its 2025 counterpart previously included pemetrexed or gemcitabine; the 2026 update includes pemetrexed, nab-paclitaxel, or gemcitabine.
A new recommendation (4.4) recommends clinicians offer telisotuzumab vedotin (Teliso-V) for patients with c-MET protein-overexpressing NSCLC.
Recommendation numbers were included in the following overview for ease of reference. To view the complete 2026 living guideline, view the full-text version.
Comparison of Recommendations
| Item | 2025 (version 2025.1.0) | 2026 (version 2026.3.0) |
|---|---|---|
| Biomarker Testing | N/A | 1.0. Biomarker testing with a validated tissue and/or blood-based broad multigene panel and a validated tissue IHC assay for PD-L1, HER2, and MET protein expression should be universally accessible for all patients diagnosed with NSCLC. |
| Nonsquamous Cell Carcinoma | ||
| PD-L1 Expression TPS ≥50% | 1.1. Clinicians should offer single-agent pembrolizumab or cemiplimab or atezolizumab. 1.2. Clinicians may offer pembrolizumab + carboplatin + pemetrexed or cemiplimab + carboplatin + pemetrexed. 1.3. Clinicians may offer atezolizumab + carboplatin + nab-paclitaxel with or without bevacizumab (in the absence of contraindications to bevacizumab). 1.4. Clinicians may offer nivolumab and ipilimumab. 1.5. Clinicians may offer nivolumab and ipilimumab plus two cycles of platinum-based chemotherapy. 1.6. Clinicians may offer durvalumab and tremelimumab plus platinum-based chemotherapy. | 1.1. Pembrolizumab or cemiplimab or atezolizumab. 1.2. Pembrolizumab + carboplatin + pemetrexed. 1.3. Cemiplimab + carboplatin + pemetrexed. 1.4. Atezolizumab + carboplatin + (nab)-paclitaxel ± bevacizumab (in the absence of contraindications to bevacizumab). 1.5. Nivolumab and ipilimumab. 1.6. Nivolumab and ipilimumab with two cycles of platinum-based chemotherapy. 1.7. Durvalumab and tremelimumab plus platinum-based chemotherapy. |
| PD-L1 Expression, TPS 1%-49% | 1.7. Clinicians should offer pembrolizumab + carboplatin + pemetrexed or cemiplimab + carboplatin + pemetrexed. 1.8. Clinicians may offer atezolizumab + carboplatin + (nab)-paclitaxel ± bevacizumab in the absence of contraindications to bevacizumab. 1.9. Clinicians may offer nivolumab and ipilimumab. 2.0. Clinicians may offer nivolumab and ipilimumab plus two cycles of platinum-based chemotherapy. 2.1. Clinicians may offer durvalumab and tremelimumab plus platinum-based chemotherapy. 2.2. For patients who are ineligible for or decline the combination of doublet platinum ± anti–PD-(L)1, clinicians may offer monotherapy with anti–PD-1. | 1.8. Pembrolizumab + carboplatin + pemetrexed. 1.9. Cemiplimab + carboplatin + pemetrexed. 1.10. Atezolizumab + carboplatin + (nab)-paclitaxel ± bevacizumab (in the absence of contraindications to bevacizumab). 1.11. Nivolumab and ipilimumab. 1.12. Nivolumab and ipilimumab plus two cycles of platinum-based chemotherapy. 1.13. Durvalumab and tremelimumab plus platinum-based chemotherapy. 1.14. Pembrolizumab monotherapy may be offered to patients who are ineligible for or decline combination therapy. |
| Unknown or Negative PD-L1 Expression, TPS <1% | 2.3. Clinicians may offer pembrolizumab + carboplatin + pemetrexed or cemiplimab + carboplatin + pemetrexed. 2.4. Clinicians may offer atezolizumab + carboplatin + (nab)-paclitaxel ± bevacizumab in the absence of contraindications to bevacizumab. 2.5. Clinicians may offer nivolumab and ipilimumab. 2.6. Clinicians may offer nivolumab and ipilimumab plus two cycles of platinum-based chemotherapy. 2.7. Clinicians may offer durvalumab and tremelimumab plus platinum-based chemotherapy. | 1.15. Pembrolizumab + carboplatin + pemetrexed. 1.16. Cemiplimab + carboplatin + pemetrexed. 1.17. Atezolizumab + carboplatin + (nab)-paclitaxel ± bevacizumab (in the absence of contraindications to bevacizumab). 1.18. Nivolumab and ipilimumab plus two cycles of platinum-based chemotherapy. 1.19. Nivolumab and ipilimumab. 1.20. Durvalumab and tremelimumab plus platinum-based chemotherapy. |
| Squamous Cell Carcinoma | ||
| PD-L1 Expression, TPS ≥50% | 3.1. Clinicians should offer single-agent pembrolizumab or cemiplimab or atezolizumab. 3.2. Clinicians may offer pembrolizumab + carboplatin + paclitaxel (or nab-paclitaxel) or cemiplimab + carboplatin + paclitaxel. 3.3. Clinicians may offer nivolumab and ipilimumab. 3.4. Clinicians may offer nivolumab and ipilimumab plus two cycles of platinum-based chemotherapy. 3.5. Clinicians may offer durvalumab and tremelimumab plus platinum-based chemotherapy. | 2.1. Single-agent pembrolizumab or cemiplimab or atezolizumab. 2.2. Pembrolizumab + carboplatin + paclitaxel (or nab-paclitaxel) or cemiplimab + carboplatin + paclitaxel. 2.3. Nivolumab and ipilimumab. 2.4. Nivolumab and ipilimumab plus two cycles of platinum-based chemotherapy. 2.5. Durvalumab and tremelimumab plus platinum-based chemotherapy. |
| PD-L1 Expression, TPS 1%-49% | 3.6. Clinicians should offer pembrolizumab + carboplatin + paclitaxel (or nab-paclitaxel) or cemiplimab + carboplatin + paclitaxel. 3.7. Clinicians may offer nivolumab and ipilimumab. 3.8. Clinicians may offer nivolumab and ipilimumab plus two cycles of platinum-based chemotherapy. 3.9. Clinicians may offer durvalumab and tremelimumab plus platinum-based chemotherapy. 4.0. For patients who are ineligible for or decline the combination of doublet platinum ± anti-PD-(L)1, clinicians may offer single-agent anti–PD-1. | 2.6. Pembrolizumab + carboplatin + paclitaxel (or nab-paclitaxel). 2.7. Cemiplimab + carboplatin + paclitaxel. 2.8. Nivolumab and ipilimumab. 2.9. Nivolumab and ipilimumab plus two cycles of platinum-based chemotherapy. 2.10. Durvalumab and tremelimumab plus platinum-based chemotherapy. 2.11. Pembrolizumab monotherapy may be offered to patients who are ineligible for or decline combination therapy. |
| Unknown or Negative PD-L1 Expression, TPS <1% | 4.1. Clinicians should offer pembrolizumab + carboplatin + paclitaxel (or nab-paclitaxel) or cemiplimab + carboplatin + paclitaxel. 4.2. Clinicians may offer nivolumab and ipilimumab. 4.3. Clinicians may offer nivolumab and ipilimumab plus two cycles of platinum-based chemotherapy. 4.4. Clinicians may offer durvalumab and tremelimumab plus platinum-based chemotherapy. | 2.12. Pembrolizumab + carboplatin + paclitaxel (or nab-paclitaxel). 2.13. Cemiplimab + carboplatin + paclitaxel. 2.14. Nivolumab and ipilimumab plus two cycles of platinum-based chemotherapy. 2.15. Nivolumab and ipilimumab. 2.16. Durvalumab and tremelimumab plus platinum-based chemotherapy. |
| General Approaches | 4.5. Patients with advanced lung cancer should be referred to interdisciplinary palliative care teams (consultation) that provide inpatient and outpatient care early in the course of disease, alongside active treatment of their cancer. 4.6. For patients who are not candidates for immune checkpoint inhibitor therapy, clinicians should offer platinum-doublet combination therapy for patients with preserved PS. 4.7. Clinicians may offer nonplatinum therapy combinations for patients who have contraindications to platinum therapy. | 3.1. Patients with advanced lung cancer should be referred to interdisciplinary palliative care teams (consultation) that provide inpatient and outpatient care early in the course of disease, alongside active treatment of their cancer. 3.2. For patients who are not candidates for immune checkpoint inhibitor therapy, clinicians should offer platinum doublet combination therapy for patients with preserved PS. 3.3. Clinicians may offer nonplatinum therapy combinations for patients who have contraindications to platinum therapy. |
| Patients with Contraindications to Bevacizumab | 4.8. Bevacizumab should be avoided for patients with SCC histologic type, clinically significant hemoptysis, inadequate organ function, ECOG PS >1, clinically significant cardiovascular disease, or medically uncontrolled hypertension. 4.9. Maintenance bevacizumab given with pemetrexed has no survival advantage and significant increased toxicity compared to maintenance pemetrexed or bevacizumab alone. | 3.4. Bevacizumab should be avoided for patients with squamous cell carcinoma histologic type, clinically significant hemoptysis, inadequate organ function, ECOG PS > 1, clinically significant cardiovascular disease, or medically uncontrolled hypertension. 3.5. Maintenance bevacizumab given with pemetrexed has no survival advantage and significantly increased toxicity compared to maintenance pemetrexed or bevacizumab alone. |
| Patients Previously Treated with Immune Checkpoint Therapy Without Chemotherapy | 5.0. Clinicians should offer platinum doublet chemotherapy. | 4.1. Clinicians should offer platinum-doublet chemotherapy. |
| Patients Previously Treated with Chemotherapy and Immune Checkpoint Therapy | 5.1. Clinicians should offer docetaxel with or without ramucirumab if the patient has already received platinum-based chemotherapy. 5.2. Clinicians may offer pemetrexed or gemcitabine if the patient has already received platinum-based chemotherapy. 5.3. Clinicians may offer trastuzumab deruxtecan for patients with HER2-overexpressing NSCLC defined as HER2 IHC 3+ (by gastric scoring). | 4.2. Clinicians should offer docetaxel with or without ramucirumab if the patient has already received platinum-based chemotherapy. 4.3. Clinicians may offer pemetrexed, nab-paclitaxel, or gemcitabine if the patient has already received platinum-based chemotherapy. 4.4. Clinicians may offer telisotuzumab vedotin (Teliso-V) for patients with c-MET protein–overexpressing NSCLC. 4.5. Clinicians may offer trastuzumab deruxtecan for patients with HER2-overexpressing NSCLC defined as HER2 IHC 3+ (by gastric scoring). |
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