In the JournalsPerspective

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

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.

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.

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