ASCO/CCO Update Guideline for Selecting Systemic Treatment in Stage IV NSCLC Without Driver Mutations

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ASCO and Cancer Care Ontario (CCO) have published an update to a joint guideline on systemic therapy for stage IV non–small cell lung cancer (NSCLC) without driver mutations.1

Nasser H. Hanna, MD

Nasser H. Hanna, MD

“The treatment of stage IV NSCLC has become increasingly more complicated, and, with the advent of immunotherapy and the identification of the PD-L1 biomarker, decision-making has become more complex,” said Guideline Co-Chair Nasser H. Hanna, MD, of the Indiana University Simon Cancer Center. “Just a few years ago, all patients with stage IV NSCLC were treated similarly. Today, there are multiple subsets [of the disease] that have been identified that must be considered for [treatment] decision-making [in patients with driver mutations such as those in EGFR or RAS].” As Dr. Hanna put it, clinicians must now consider tumor histology, programmed cell death ligand 1 (PD-L1) score, eligibility for immunotherapy, appropriateness for chemoimmunotherapy, and eligibility for bevacizumab before selecting a treatment paradigm.

Recommendations Based on Emerging Evidence

In this guideline, researchers provided a partial update and revision to the 2017 ASCO/CCO guideline, providing recommendations based on emerging evidence regarding systemic therapy in stage IV NSCLC without effectively targeted driver alterations and with known EGFR and ALK status (in addition to PD-L1 tumor proportion score [TPS] test results). New recommendations focus on the use of immune checkpoint therapy, chemotherapy, and anti-VEGF agents.

Gregory Masters, MD, FACP, FASCO

Gregory Masters, MD, FACP, FASCO

“There have been a number of new developments in the management of advanced NSCLC,” said Guideline Co-Chair Gregory Masters, MD, FACP, FASCO, of the Helen F. Graham Cancer Center and Research Institute. “Some of them involve targeted therapies for patients with driver mutations, but others involve combinations of chemotherapy and immunotherapy and new immunotherapy indications and combinations.”

Based on data from the KEYNOTE-042 trial, which demonstrated a greater overall survival with single-agent pembrolizumab compared with a chemotherapy doublet,2 the updated guideline now recommends offering single-agent pembrolizu­mab to patients with high PD-L1 expression (TPS ≥ 50%), nonsquamous cell carcinoma and an Eastern Cooperative Oncology Group performance status of 0 to 1. The KEYNOTE-407 study also formed the basis for another recommendation in the guideline, which states that clinicians may wish to consider offering pembrolizumab/carboplatin/(paclitaxel or nab-paclitaxel) to patients with squamous cell carcinoma, high PD-L1 expression, and a performance status of 0 to 1.

Recent data from the IMpower150 trial also played a role in the updated recommendations.3 Based on data from this trial, the guideline now recommends offering atezolizumab/carboplatin/paclitaxel/bevacizumab to patients with nonsquamous cell cancer and high PD-L1 expression and without contraindications to bevacizumab. Likewise, the guideline also recommends that clinicians consider offering atezolizumab/carboplatin/nab-paclitaxel to patients with high PD-L1 expression nonsquamous cell carcinoma, based on data from the IMpower130 trial.4

According to the guideline authors, there are insufficient data available to recommend any other checkpoint inhibitor and any immune checkpoint inhibitor combinations with chemotherapy as a first-line approach.

PD-L1 Testing

A primary consideration in the guideline was the importance of PD-L1 testing to guide immunotherapy approaches in the first-line setting and beyond, Dr. Hanna said. In addition, he emphasized the importance of documenting PD-L1 status in every patient, because it can be an important biomarker for offering the most effective treatment.

“Much of the research has focused on immunotherapy and selecting optimal patients for immunotherapy vs chemotherapy vs combinations,” Dr. Masters said. “We still do not have a single universal test to guide immunotherapy, but PD-L1 testing has received the most attention in guiding options.

“In PD-L1–low or –negative populations, combination chemotherapy and immunotherapy has shown the most activity to date,” Dr. Masters continued. “We outlined how randomized trials have shown that median survival has significantly improved over the past several years so that many patients are living beyond 24 months. There is a significant group of patients who will survive 5 years or more with the incorporation of immunotherapy into their treatment regimen.”

Future Updates

When asked which areas of the guideline need further attention, Dr. Masters stated that a future update might include information on the optimal selection of patients for immunotherapy, combination therapy with chemotherapy and immune checkpoint inhibitors, or combination immunotherapy. Dr. Hanna added that more data are needed on the optimal duration of therapy and the treatment of patients who have experienced disease progression before or after immunotherapy. These additional data may help inform future guidelines for this population of patients with advanced disease.

“The various drugs that have been developed as immune checkpoint inhibitors are still being evaluated, and, eventually, we would like to see studies comparing these agents with and without chemotherapy,” Dr. Masters said. “Certainly, there is a need for ongoing investigation for patients who receive immunotherapy and then [experience disease progression]. This population has limited options for effective therapies, and clinical trial participation is crucial to delineate the best course of action.” 

DISCLOSURE: For full disclosures of the study authors, visit


1. Hanna NH, Schneider BJ, Temin S, et al: Therapy for stage IV non-small cell lung cancer without driver alterations: ASCO and OH (CCO) joint guideline update. J Clin Oncol. January 28, 2020 (early release online).

2. Mok TSK, Wu YL, Kudaba I, et al: Pembrolizumab vs chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): A randomised, open-label, controlled, phase III trial. Lancet 393:1819-1830, 2019.

3. Socinski MA, Jotte RM, Cappuzzo F, et al: Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med 378:2288-2301, 2018.

4. West H, McCleod M, Hussein M, et al: Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): A multicentre, randomised, open-label, phase III trial. Lancet Oncol 20:924-937, 2019.

Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, January 28, 2020. All rights reserved.