New Therapy Guideline Marks New Era for Stage IV NSCLC Patients

The American Society of Clinical Oncology (ASCO) is issuing a new clinical practice guideline that more adequately clarifies the role of immunotherapy in the treatment of patients with advanced non–small-cell lung cancer (NSCLC). The update provides new recommendations on the use of targeted therapies for patients with changes in EGFR, ALK, and ROS1 genes.

ASCO published the last guideline on systemic therapy for stage IV NSCLC in 2015. To develop this update, an expert panel with multidisciplinary representation reviewed medical literature published between February 2014 and December 2016. The new recommendations are based on 14 randomized controlled clinical trials, and earlier-phase trials were also taken under advisement.

“The major changes in the NSCLC guidelines since 2015 include further clarification on applying molecular testing and using targeted therapy, as well as the new immunotherapy drugs, especially checkpoint inhibitors, which have shown to be helpful in patients, especially with PD-L1 positivity,” said Gregory Masters, MD, a medical oncologist in Delaware and co-chair of the expert panel that developed the guideline update.

The new update recommends that if a patient has low PD-L1 expression, clinicians should offer standard chemotherapy as first-line therapy. Pembrolizumab alone is recommended for patients with high PD-L1 expression. Other checkpoint inhibitors, combinations of checkpoint inhibitors, and immune checkpoint therapy with chemotherapy are not recommended.

First-line recommendations for targeted therapy from the 2015 guideline remain the same for patients with EGFR mutation–positive, ALK rearrangement–positive, or ROS1 rearrangement–positive tumors.

For second-line therapy in patients with high PD-L1 expression who have had no prior immunotherapy, clinicians should use single-agent nivolumab, pembrolizumab, or atezolizumab, according to the update. However, if the tumor has low PD-L1 expression or the PD-L1 expression level is unknown, clinicians should use nivolumab, atezolizumab, or chemotherapy. Other checkpoint inhibitors, combinations of checkpoint inhibitors, and immune checkpoint therapy with chemotherapy are not recommended.

“We have tried to help refine recommendations for individual patients based on their specific cancer subtype and molecular profile to improve quality of life and extend survival,” said Masters.

For patients with sensitizing EGFR mutations and progression following first-line EGFR targeted therapy, osimertinib is recommended, if the tumor has T790M mutation. However, if the tumor lacks the T790M mutation, then chemotherapy is recommended.

Patients with ROS1 gene rearrangement may be offered crizotinib if they have not had prior crizotinib, or chemotherapy if they have had prior crizotinib. The authors noted that there are insufficient data to recommend for or against immunotherapy in the third-line setting.

“The most important take-home message for oncologists is to recognize the significance of molecular characterization of NSCLC for each individual patient. This allows us to take advantage of all available treatment options including chemotherapy, targeted therapy, and immunotherapy, and to best match these options to the individual’s unique tumor profile,” Masters told OncoTherapy Network.