ASCO Updates Treatment Guidelines for Advanced NSCLC

Nasser Hanna, MD

ASCO has updated its guidelines for first- and second-line treatment of patients with stage IV non—small cell lung cancer (NSCLC). The organization has created new recommendations regarding the use of immunotherapy, and updated advice on targeted therapies for patients with mutations in the EGFR, ALK, or ROS1 genes.

“Treatment for lung cancer has become increasingly more complex over the last several years,” Nasser Hanna, MD, co-chair of the expert panel that developed the guideline update, said in a press release. “This guideline update provides oncologists the tools to choose therapies that are most likely to benefit their patients.”

The guidelines were last updated in 2015. A multidisciplinary expert panel reviewed medical literature published from February 2014 to December 2016 to develop this year’s update. The recommendations are based on 14 randomized controlled clinical trials providing “potentially practice-changing evidence.” In this case, the updates were a direct response to developments in immunotherapy over the past 2 years.

In first-line therapy, ASCO strongly recommends pembrolizumab (Keytruda) monotherapy for patients with high PD-L1 expression (tumor proportion score [TPS] ≥50%). Patients with low PD-L1 (TPS <50%) should be treated with standard platinum-based chemotherapy with or without bevacizumab (Avastin). The organization gave a weak recommendation to the use of non—platinum-based treatment.

ASCO does not recommend other checkpoint inhibitors, combinations of checkpoint inhibitors, and immune checkpoint therapy with chemotherapy in the frontline setting.

ASCO said there is insufficient evidence to recommend bevacizumab in combination with pemetrexed plus carboplatin in the first line.

For patients with EGFR mutation—positive, ALK rearrangement—positive or ROS1 rearrangement—positive tumors in the first line, ASCO’s recommendations are unchanged.

The changes are more extensive for second-line treatment. For patients who have received first-line chemotherapy without prior immune checkpoint therapy, ASCO strongly recommends monotherapy with pembrolizumab, nivolumab (Opdivo), or atezolizumab (Tecentriq) in those patients whose tumors have high PD-L1 expression (TPS ≥1%). Physicians should use single-agent nivolumab, atezolizumab, or a chemotherapy regimen for patients with negative or unknown PD-L1 expression (TPS <1%).

As in the frontline, ASCO does not recommend other checkpoint inhibitors, combinations of checkpoint inhibitors, or immune checkpoint therapy with chemotherapy in the second-line setting.

Physicians should offer standard second-line chemotherapy to patients who previously received a first-line immune checkpoint inhibitor.

ASCO strongly recommends osimertinib (Tagrisso) for patients with a sensitizing EGFR mutation and progression following a first-line EGFR targeted therapy if the tumor has a T790M mutation. Patients whose tumors do not have the T790M mutation should undergo treatment with chemotherapy.

ASCO says that patients with a ROS1 gene0 rearrangement may be offered crizotinib (Xalkori) if they have not been treated with the ALK-inhibitor previously. Patients with prior crizotinib treatment may be offered chemotherapy.

The organization added that there are insufficient data to recommend for or against immunotherapy in the third-line setting, and called for administration of concurrent palliative care starting at diagnosis.

“Our patients rely on us to keep up with the most effective and best tolerated therapies to help manage this devastating disease,” Gregory Masters, MD, co-chair of the expert panel that developed the guideline update, said in a press release. “Knowing when to use targeted therapies or immunotherapy in place of more toxic chemotherapy can help improve the quality of life of our patients.”

ASCO noted that these recommendations are based on the idea that patients have undergone molecular testing prior to initiating treatment. Other organizations recommend EGFR/ALK/ROS1 testing and clinical trials for PD-1 and PD-L1 testing.

The organization also noted that while immunotherapy can provide a survival benefit in some cases, not every patient will respond to treatment, and physicians still do not fully understand optimal sequencing of immune checkpoint therapy and other recommended agents.

Hanna N, Johnson D, Temin S, et al. Systemic therapy for stage IV non—small-cell lung cancer: American Society of Clinical Oncology clinical practice guideline update [published online August 14, 2017]. J Clin Oncol. doi: 10.1200/JCO.2017.74.6065.