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ASCO updates guideline on systemic therapy for non-small cell lung cancer

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August 14, 2017

Gregory A. Masters

An updated ASCO clinical practice guideline clarifies the appropriate use of immunotherapy and provides new recommendations on the use of targeted therapy for patients with stage IV non-small cell lung cancer.

The evidence-based recommendations focus on the use of immunotherapy in the first- and second-line settings, and targeted therapies for patients with changes in tumor EGFR, ALK and ROS1 genes. Not enough evidence existed to recommend for or against immunotherapy in the third-line setting.

“Knowing when to use targeted therapies or immunotherapy in place of more toxic chemotherapy can help improve the quality of life of our patients,” Gregory A. Masters, MD, co-chair of the ASCO expert panel that developed the guideline, attending physician at Helen F. Graham Cancer Center and associate professor at Thomas Jefferson University Medical School, said in a press release.

To update the guideline — last published in 2015 — the panel conducted a systematic review of randomized, controlled clinical trials published between February 2014 and December 2016. Fourteen clinical trials provided the evidence for the recommendations.

The guideline contains the following recommendations for first-line treatment for patients without EGFR, ALK and ROS1 mutations:

  • Pembrolizumab (Keytruda, Merck) alone is recommended for patients with high PD-L1 expression in the tumor;
  • Patients with low PD-L1 expression should be offered standard chemotherapy; and
  • All other checkpoint inhibitors, combinations of checkpoint inhibitors and immune checkpoint therapy with chemotherapy are not recommended.

The guideline maintains the first-line recommendations from the 2015 guideline should be followed for patients with EGFR-, ALK- or ROS1-positive tumors.

The panel made the following recommendations for second-line treatment:

  • Single-agent nivolumab (Opdivo, Bristol-Myers Squibb), pembrolizumab or atezolizumab (Tecentriq, Genentech) is recommended for patients with high PD-L1 expression who have not received prior immunotherapy;
  • If PD-L1 expression is low or unknown, then nivolumab, atezolizumab or chemotherapy is recommended;
  • All other checkpoint inhibitors, combinations of checkpoint inhibitors, and immune checkpoint therapy with chemotherapy are not recommended;
  • Patients who received checkpoint inhibitors as first-line therapy should be offered standard chemotherapy;
  • Patients who cannot receive an immune checkpoint inhibitor after chemotherapy should be offered docetaxel; pemetrexed is recommended for patients with nonsquamous NSCLC;
  • Among patients with sensitizing EGFR mutations, those who progressed after first-line EGFR-targeted therapy and harbor a T790M mutation should receive osimertinib (Tagrisso, AstraZeneca). If no T790M mutation is present, then standard chemotherapy should be offered;
  • Patients with ROS1 gene arrangement may be offered crizotinib (Xalkori, Pfizer) if they have not previously received it. If patients received prior crizotinib therapy, chemotherapy should be offered; and
  • Concurrent palliative care should commence at diagnosis.

“Treatment for lung cancer has become increasingly more complex over the last several years,” Nasser Hanna, MD, co-chair of the ASCO expert panel that developed the guideline and professor of medicine at Indiana University School of Medicine, said in the release. “This guideline update provides oncologists the tools to choose therapies that are most likely to benefit their patients.” – by Melinda Stevens

Disclosures: Masters reports he has no relevant financial disclosures. Hanna reports he has received institutional research funding from Bristol-Myers Squibb and Merck KGaA. Please see the full guideline for a list of all other authors’ relevant financial disclosures.

itj+ Perspective

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Perspective

This is an exciting time in lung cancer treatment. We have new developments for the treatment of NSCLC — especially immunotherapy and targeted therapy. This ASCO update is important because it relates the major clinical trials that have come out in the last couple of years. This is a way for a clinician to go through the data and get a sense of the recommendations.

The role of immunotherapy is an important change. Immunotherapy essentially removes the brakes of the immune system, allowing it to attack the cancer. Lung cancer is one of the diseases in which we are making great progress in its treatment with immunotherapy. There are now some patients who should receive immunotherapy as first-line treatment, which the ASCO guidelines address.

Among patients diagnosed with advanced disease, clinicians should check for molecular targets like EGFR, ALK and ROS1 mutations and gene rearrangements. Clinicians also should assess PD-1 and PD-L1 expression to know when to give immunotherapy.

Lung cancer is the second most common cancer in both men and women, but it’s the number one cause of mortality, in part because we haven’t had good treatments for advanced-stage disease. Immunotherapy has improved OS compared with standard chemotherapy in second-line treatment. For patients who have a high PD-L1 expression, immunotherapy improves OS compared with chemotherapy in first-line treatment. This marks the first change in the way we treat lung cancer in a long time.

One other thing to note is the FDA approved the combination of immunotherapy and chemotherapy for patients with nonsquamous cell lung cancer, but the ASCO guidelines do not yet recommend that be used for everyone. The FDA approved the combination of immunotherapy with chemotherapy based on a small number of patients in a phase 2 study. We don’t have survival data yet on this combination, and it’s important we continue to get more data on the combination before we recommend it to all of our patients.

Sarah Gordon, DO

Virginia Commonwealth University Massey Cancer Center

Disclosure: Gordon reports no relevant financial disclosures.