The American Society of Clinical Oncology (ASCO) just updated its non-small cell lung cancer (NSCLC) living guidelines, Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations and Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations to version 2026.3.1. The update comes with a few changes. In the stage IV NSCLC with driver alterations guideline, recommendation 1.2 now features a qualifying statement that lazertinib monotherapy may be offered as an alternative treatment option for patients unable to access osimertinib. Additionally, recommendation 1.4 now suggests clinicians may offer amivantamab plus lazertinib, which also affects recommendations 1.3 and 1.5. In the stage IV NSCLC without driver alterations guideline, recommendations 1.8, 1.14, 1.21 were adjusted to include the suggestion that clinicians may offer retifanlimab plus platinum-based chemotherapy.

Outlined below, we feature the handful of new updates introduced in the recent 2026.3.1 update, alongside the previous version of the guidelines (version 2026.3.0). For the most thorough look at each guideline, visit the guideline summary pages linked above and navigate to the “full text” tab, near the top of each page.

Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations
2026.3.12026.3.0
Recommendation 1.2: Clinicians should offer osimertinib to patients not pursuing combination therapy (Evidence quality: Moderate; Strength of recommendation: Strong).

Qualifying Statement forRecommendations 1.2: For patients unable to access osimertinib, lazertinib monotherapy may be offered as an alternative treatment option if available.		Recommendation 1.2: Clinicians should offer osimertinib to patients not pursuing combination therapy (Evidence quality: Moderate; Strength of recommendation: Strong).
Recommendation 1.4: For other activating EGFR alterations (G719X, L861Q, S768I), clinicians may offer amivantamab plus lazertinib (Evidence quality: Low; Strength of recommendation: Conditional).

Qualifying Statement for Recommendations 1.3, 1.4 and 1.5: Recommendations 1.3, 1.4 and 1.5 exclude exon 20 insertion alterations, T790M.		Recommendation 1.3: For other activating EGFR alterations (G719X, L861Q, S768I), clinicians may offer afatinib (Evidence quality: Moderate; Strength of recommendation: Strong).

Recommendation 1.4: or osimertinib (Evidence quality: Low; Strength of recommendation: Conditional).

Qualifying Statement for Recommendations 1.3 and 1.4: Recommendations 1.3 and 1.4 exclude exon 20 insertion alterations, T790M.
Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations
2026.3.12026.3.0
Recommendations 1.8, 1.14, 1.21. Clinicians may offer retifanlimab plus platinum-based chemotherapy (Evidence quality: Moderate; Strength of recommendation: Conditional).Recommendation 1.8: Pembrolizumab + carboplatin + pemetrexed (Evidence quality: Moderate; Strength of recommendation: Strong).

Recommendation 1.14: Pembrolizumab monotherapy may be offered to patients who are ineligible for or decline combination therapy (Evidence quality: Moderate; Strength of recommendation: Conditional).

Recommendation 1.21: N/A

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