The most common type of lung cancer is non-small cell lung cancer (NSCLC). A sub-type of NSCLC, squamous cell carcinoma, is strongly associated with smoking. This type of lung cancer is usually located in the bronchi. Symptoms include voice changes, cough, shortness of breath, chest pain, and/or weight loss. Survival can be improved for patients with stage IV squamous cell NSCLC with immunotherapy used either alone or in combination with chemotherapy.
In this guidelines side-by-side comparison, we look at the latest clinical practice guidelines from the American Society of Clinical Oncology (ASCO) and the Society for Immunotherapy of Cancer (SITC) on first-line immunotherapy options for stage IV NSCLC.
Guidelines for Comparison
| Item | Therapy for Stage IV Non–Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2025.1 | Addendum 1: Society for Immunotherapy of Cancer (SITC) Clinical Practice Guideline on Immunotherapy for the Treatment of Lung Cancer and Mesothelioma |
|---|---|---|
| Authoring Society | American Society of Clinical Oncology | Society for Immunotherapy of Cancer |
| Publication Date | July 2025 | July 2025 |
| Graded Recommendations | Yes | Yes |
| Links | Summary / Full Text | Summary / Full Text |
Key Takeaways
Both of the articles reviewed today are updates to living guidelines, which undergo systematic reviews to stay up-to-date on practice changing evidence. In addition to first line immunotherapy options for stage IV squamous cell NSCLC, ASCO also updated one recommendation on second-line/subsequent line treatment for stage IV NSCLC and SITC updated recommendations for tumor mutational burden (TMB) and microsatellite instability (MSI) as tumor-agnostic indicators for immune checkpoint inhibitor (ICI) therapy, treatment recommendations for other stages of NSCLC (IB, II, IIIA), treatment of relapsed or refractory small cell lung cancer (SCLC), first line treatment of mesothelioma, and monitoring and treatment of immune-related toxicities for patients taking tarlatamab. Only first-line immunotherapy options for stage IV squamous cell NSCLC were reviewed in this article. We encourage you to review the full guidelines, found at the links above, for a more complete understanding of the recommendations.
Now to review and compare the updated and new recommendations for immunotherapy in patients with stage IV squamous cell NSCLC.
- ASCO provided 1 updated recommendations for first-line immunotherapy options for patients with stage IV NSCLC:
- First-line treatment options for patients with good performance status, any histology, and any PD-L1 expression:
- May offer nivolumab and ipilimumab plus two cycles of platinum-based chemotherapy.
- This is in line with SITC who also recommends offering nivolumab and ipilimumab with or without chemotherapy as a treatment option. The recommendation does not state a preferred number of cycles.
- First-line treatment options for patients with good performance status, any histology, and any PD-L1 expression:
- SITC added 2 new recommendations for patients with metastatic NSCLC:
- For patients with NSCLC with no EGFR, ALK, or ROS1 aberrations that is metastatic or locally advanced where patients are not candidates for surgical resection or definitive chemoradiation, first-line treatment with cemiplimab plus platinum-based chemotherapy may be considered.
- ASCO also offers cemiplimab with doublet chemotherapy as a first-line treatment option.
- For patients with metastatic NSCLC with no sensitizing EGFR mutation or ALK genomic tumor aberrations, tremelimumab plus durvalumab with platinum-based chemotherapy may be considered.
- ASCO recommendations align with this, offering tremelimumab with durvalumab and platinum-based chemotherapy as first-line treatment options.
First-Line Treatment Options for Stage IV NSCLS Without Actionable Genetic Alterations
| Category | ASCO | SITC |
|---|---|---|
| PD-L1 TPS ≥50% | Pembrolizumab Atezolizumab Cemiplimab Pembrolizumab + carboplatin + paclitaxel (or nab-paclitaxel) Cemiplimab + carboplatin + paclitaxel Nivolumab + ipilimumab Nivolumab + ipilimumab + two cycles of platinum-based chemotherapy Durvalumab + tremelimumab + platinum-based chemotherapy | Pembrolizumab Atezolizumab Cemiplimab Pembrolizumab + chemotherapy Atezolizumab + chemotherapy (with or without bevacizumab) Cemiplimab + chemotherapy Nivolumab + ipilimumab (with or without chemotherapy) Durvalumab + tremelimumab + chemotherapy |
| PD-L1 expression TPS 1%-49% | Pembrolizumab + carboplatin + paclitaxel (or nab-paclitaxel) Cemiplimab + carboplatin + paclitaxel Nivolumab + ipilimumab Nivolumab + ipilimumab + two cycles of platinum-based chemotherapy Durvalumab + tremelimumab + platinum-based chemotherapy Single-agent anti-PD-1 for patients who are ineligible or decline combination therapy with doublet platinum with or without and anti-PD-(L)1 | Pembrolizumab + chemotherapy Atezolizumab + chemotherapy (with or without bevacizumab) Cemiplimab + chemotherapy Nivolumab + ipilimumab (with or without chemotherapy) Durvalumab + tremelimumab + chemotherapy |
| Unknown or negative PD-L1 expression TPS < 1% | Pembrolizumab + carboplatin + paclitaxel (or nab-paclitaxel) Cemiplimab + carboplatin + paclitaxel Nivolumab + ipilimumab Nivolumab + ipilimumab + two cycles of platinum-based chemotherapy Durvalumab + tremelimumab + platinum-based chemotherapy | Pembrolizumab + chemotherapy Atezolizumab + chemotherapy (with or without bevacizumab) Cemiplimab + chemotherapy Nivolumab + ipilimumab (with or without chemotherapy) Durvalumab + tremelimumab + chemotherapy |
Comparison of Recommendations
| NSCLC Without Actionable Mutations | ASCO | SITC |
|---|---|---|
| NSCLC Without Actionable Mutations | Stage IV NSCLC without driver alterations: First-line treatment options for patients with good performance status, any histology, and any PD-L1 expression: Clinicians may offer nivolumab and ipilimumab plus two cycles of platinum-based chemotherapy. | For patients with NSCLC with no EGFR, ALK, or ROS1 aberrations that is metastatic or locally advanced where patients are not candidates for surgical resection or definitive chemoradiation, first-line treatment with cemiplimab plus platinum-based chemotherapy may be considered. For patients with metastatic NSCLC with no sensitizing EGFR mutation or ALK genomic tumor aberrations, tremelimumab plus durvalumab with platinum-based chemotherapy may be considered. |
| PD-L1 Expression, TPS ≥50% | 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. | For patients with metastatic NSCLC with no actionable mutations and TPS ≥50%, the panel recommends first-line pembrolizumab, atezolizumab, or cemiplimab monotherapy, with consideration for chemo-immunotherapy for patients with high tumor disease burden or worrisome symptoms. |
| PD-L1 Expression, TPS 1% – 49$ | Clinicians should 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. 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. | For patients with metastatic NSCLC with no actionable mutations and TPS <50%, pembrolizumab with chemotherapy, atezolizumab with chemotherapy (with or without bevacizumab), or nivolumab with ipilimumab with or without 2 cycles of chemotherapy (in select cases) should be used. For patients with metastatic NSCLC with no actionable mutations and tumor PD-L1 expression 1%–49% who are ineligible for or refuse chemotherapy, pembrolizumab monotherapy may be considered. |
| PD-L1 Expression, TPS ≤1% | Clinicians should 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. | For patients with metastatic NSCLC with tumor PD-L1 expression ≤1% and baseline brain metastases or squamous histology nivolumab in combination with ipilimumab may be considered. |
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