Therapy for Stage IV Non–Small Cell Lung Cancer Without Driver Alterations

Biomarker testing with a validated tissue and/or blood based broad multi-gene 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.

Clinicians should offer single-agent pembrolizumab or cemiplimab or atezolizumab.

Clinicians may offer pembrolizumab + carboplatin + pemetrexed.

Clinicians may offer cemiplimab + carboplatin + pemetrexed.

Clinicians may offer atezolizumab + carboplatin + (nab)-paclitaxel ± bevacizumab (in the absence of contraindications to bevacizumab).

Clinicians may offer nivolumab and ipilimumab.

Clinicians may offer nivolumab and ipilimumab with two cycles of platinum-based chemotherapy.

Clinicians may offer durvalumab and tremelimumab plus platinum-based chemotherapy.

Clinicians may offer retifanlimab plus platinum-based chemotherapy.

Clinicians should offer pembrolizumab + carboplatin + pemetrexed.

Clinicians should offer cemiplimab + carboplatin + pemetrexed.

Clinicians may offer atezolizumab + carboplatin + (nab)-paclitaxel ± bevacizumab (in the absence of contraindications to bevacizumab).

Clinicians may offer nivolumab and ipilimumab.

Clinicians may offer nivolumab and ipilimumab plus two cycles of platinum based chemotherapy.

Clinicians may offer durvalumab and tremelimumab plus platinum-based chemotherapy.

Clinicians may offer retifanlimab plus platinum-based chemotherapy.

Pembrolizumab monotherapy may be offered to patients who are ineligible for or decline combination therapy.

Clinicians may offer pembrolizumab + carboplatin + pemetrexed.

Clinicians may offer cemiplimab + carboplatin + pemetrexed.

Clinicians may offer atezolizumab + carboplatin + (nab)-paclitaxel ± bevacizumab (in the absence of contraindications to bevacizumab).

Clinicians may offer nivolumab and ipilimumab plus two cycles of platinum-based chemotherapy.

Clinicians may offer nivolumab and ipilimumab.

Clinicians may offer durvalumab and tremelimumab plus platinum-based chemotherapy.

Clinicians may offer retifanlimab plus platinum-based chemotherapy.

Clinicians should offer single-agent pembrolizumab or cemiplimab or atezolizumab.

Clinicians may offer pembrolizumab + carboplatin + paclitaxel (or nab-paclitaxel) or cemiplimab + carboplatin + paclitaxel.

Clinicians may offer nivolumab and ipilimumab.

Clinicians may offer nivolumab and ipilimumab plus two cycles of platinum-based chemotherapy.

Clinicians may offer durvalumab and tremelimumab plus platinum-based chemotherapy.

Clinicians should offer pembrolizumab + carboplatin + paclitaxel (or nab-paclitaxel).

Clinicians should offer cemiplimab + carboplatin + paclitaxel.

Clinicians should offer nivolumab and ipilimumab.

Clinicians should offer nivolumab and ipilimumab plus two cycles of platinum-based chemotherapy.

Clinicians may offer durvalumab and tremelimumab plus platinum-based chemotherapy.

Pembrolizumab monotherapy may be offered to patients who are ineligible for or decline combination therapy.

Clinicians should offer pembrolizumab + carboplatin + paclitaxel (or nab-paclitaxel).

Clinicians should offer cemiplimab + carboplatin + paclitaxel.

Clinicians may offer nivolumab and ipilimumab plus two cycles of platinum-based chemotherapy.

Clinicians may offer nivolumab and ipilimumab.

Clinicians may offer durvalumab and tremelimumab plus platinum-based chemotherapy.

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.

For patients who are not candidates for immune checkpoint inhibitor therapy, clinicians should offer platinum doublet combination therapy for patients with preserved PS.

Clinicians may offer nonplatinum therapy combinations for patients who have contraindications to platinum therapy.

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.

Maintenance bevacizumab given with pemetrexed has no survival advantage and significant increased toxicity compared to maintenance pemetrexed or bevacizumab alone.

Clinicians should offer platinum doublet chemotherapy.

Clinicians should offer docetaxel with or without ramucirumab if the patient has already received platinum-based chemotherapy.

Clinicians may offer pemetrexed, nab-paclitaxel, or gemcitabine if the patient has already received platinum-based chemotherapy.

Clinicians may offer telisotuzumab vedotin (Teliso-V) for patients with c-Met protein-overexpressing NSCLC.

Clinicians may offer trastuzumab deruxtecan for patients with human epidermal growth factor receptor 2 (HER2)– overexpressing NSCLC defined as HER2 immunohistochemistry (IHC) 31 (by gastric scoring).