The presence or absence of mutations in advanced non-small cell lung cancer (NSCLC) should guide selection of first-line systemic therapy, according to an updated clinical guideline from the American Society of Clinical Oncology.

Patients with squamous-cell tumors that have no gene alterations should begin treatment with combination platinum-based cytotoxic chemotherapy, so long as they have good performance status (0 or 1). Optionally, bevacizumab (Avastin) may be added when the platinum agent is carboplatin. For patients with performance status 2, either chemotherapy or palliative care alone is an acceptable option.

In the presence of sensitizing EGFR mutations, appropriate first-line therapy is afatinib (Gilotrif), erlotinib (Tarceva), or gefitinib (Iressa). Treatment should begin with crizotinib (Xalkori) when patients have tumors with ALK or ROS1rearrangements, as published online in the Journal of Clinical Oncology.

Patients who respond to treatment have the option of continuing the same regimen as maintenance therapy, switching to a different therapy, or taking a break from therapy.

“Although there is no cure for patients with stage IV non-small cell lung cancer, various treatment options are available that can help patients control their cancer longer,” guideline panel co-chair Gregory Masters, MD, of Christiana Care Health System in Newark, Del., said in a statement. “This guideline will help doctors choose the most appropriate therapies, depending on the biology of the tumor and the patient’s general well-being.”

For first-line conventional chemotherapy for nonsquamous NSCLC, also favors platinum-containing regimens. The panel noted that use of nonplatinum doublets has weak supporting evidence. Additionally, “there are no FDA-approved nonplatinum regimens,” the authors pointed out.

The guideline addresses treatment options for multiple combinations of tumor mutation status, performance status, and histologic subtype, as well as quality of response (if any) and the selection of maintenance therapy.

The panel decided to remove a previous recommendation that allowed clinicians to “consider addition of cetuximab (Erbitux) to cisplatin-vinorelbine in first-line therapy in patients with EGFR-positive tumor.” Cetuximab has no regulatory approval for NSCLC in the United States, Canada, or Europe, and a recent trial of a cetuximab-containing combination ended in a negative result, the panel noted.

Options for second-line therapy included docetaxel, erlotinib, and gefitinib, plus pemetrexed (Alimta) as an additional option for patients with nonsquamous tumors. Patients with EGFR-mutant tumors can receive chemotherapy or a different EGFR inhibitor, depending on response to initial therapy. Crizotinib or chemotherapy is appropriate for patients with ALKrearrangements.

For third-line therapy, the panel backed the existing ASCO recommendation of erlotinib for patients with performance status 0 to 3 and no prior exposure to erlotinib or gefitinib. The authors found data insufficient to recommend for or against cytotoxic chemotherapy in third line.

The ASCO panel supported early palliative care, alone or in addition to primary therapy, throughout the guideline.

“Early palliative care is associated with improved survival of patients with advanced lung cancer,” panel co-chair David H. Johnson, MD, of the University of Texas Southwestern Medical Center in Dallas, said in the ASCO statement. “Hospice care also improves patient quality of life and reduces caregiver distress.”