SUMMARY: Lung cancer is the second most common cancer in both men and women and accounts for about 13% of all new cancers and 27% of all cancer deaths. The American Cancer Society estimates that for 2017 about 222,500 new cases of lung cancer will be diagnosed and over 155,000 patients will die of the disease. Lung cancer is the leading cause of cancer-related mortality in the United States. ASCO published the last clinical practice guideline update on systemic therapy for patients with Stage IV Non Small Cell Lung Cancer (NSCLC), in 2015. With the many advances in the management of these patients and availability of new practice changing evidence since the last publication, the latest ASCO guideline has been revised. The ASCO NSCLC Expert Panel updated their recommendations based on a systematic review of 14 randomized controlled trials from February 2014 to December 2016 and six nonrandomized studies on systemic therapy. This guideline is applicable to patients who had received molecular testing for EGFR/ALK/ROS1, as well as Programmed Death Ligand 1 (PD-L1), and clinicians know the test results.
Guideline Question: What systemic therapy treatment options should be offered to patients with Stage IV NSCLC, depending on the subtype of the patient’s cancer?
Target Population: Patients with Stage IV NSCLC.
Target Audience: Oncology care providers (including primary care physicians, specialists, nurses, social workers, and any other relevant member of a comprehensive multidisciplinary cancer care team), patients, and their caregivers.
Key Points:
1) There is no cure for patients with Stage IV NSCLC.
2) Decisions regarding chemotherapy should not be made based on age alone.
Recommendations: First Line Treatment for Patients
Patients with Non-Squamous Cell Carcinoma without a tumor EGFR-sensitizing mutation or ALK or ROS1 gene rearrangement and with a Performance Status (PS) of 0 or 1 (and appropriate PS of 2):
1) With high PD-L1 expression (Tumor Proportion Score [TPS] 50% or more) and no contraindications, single-agent Pembrolizumab is recommended.
2) With low PD-L1 expression (TPS less than 50%), a variety of combination cytotoxic chemotherapies (with or without Bevacizumab, if patients are receiving Carboplatin and Paclitaxel) are recommended.
3) There is insufficient evidence to recommend Bevacizumab in combination with Pemetrexed plus Carboplatin.
4) Other checkpoint inhibitors, combination checkpoint inhibitors, or immune checkpoint therapy with chemotherapy are not recommended.
5) With PS of 2, combination or single agent therapy or palliative care alone may be used.
Patients with Squamous Cell Carcinoma without a tumor EGFR-sensitizing mutation or ALK or ROS1 gene rearrangement and with a PS of 0 or 1 (and appropriate PS of 2):
1) With high PD-L1 expression (TPS 50% or more) and no contraindications, single agent Pembrolizumab is recommended.
2) With low PD-L1 expression (TPS less than 50%), a variety of combination cytotoxic chemotherapies are recommended.
3) Other checkpoint inhibitors, combination checkpoint inhibitors, or immune checkpoint therapy with chemotherapy are not recommended.
4) With PS of 2, combination or single agent therapy or palliative care alone may be used.
5) With Squamous NSCLC treated with Cisplatin and Gemcitabine, the Panel neither recommends for nor recommends against the addition of Necitumumab to chemotherapy.
With sensitizing EGFR mutations, Afatinib, Erlotinib, or Gefitinib is recommended.
With ALK gene rearrangements, Crizotinib is recommended.
With ROS1 rearrangement, Crizotinib is recommended.
Recommendations: Second Line Treatment for Patients
Without a tumor EGFR-sensitizing mutation or ALK or ROS1 gene rearrangement and with PS of 0 or 1 (and appropriate PS of 2):
1) In patients with high PD-L1 expression (TPS 1% or more), no contraindications, who received first line chemotherapy and have not received prior immune therapy, single agent Nivolumab, Pembrolizumab, or Atezolizumab is recommended.
2) In patients with negative or unknown tumor PD-L1 expression (TPS less than 1%), no contraindications and who received first line chemotherapy, single agent Nivolumab, or Atezolizumab, or a variety of combination cytotoxic chemotherapies are recommended.
3) Other checkpoint inhibitors, combination checkpoint inhibitors, and immune checkpoint therapy with chemotherapy are not recommended.
4) In patients who received an immune checkpoint inhibitor as first line therapy, a variety of combination cytotoxic chemotherapies are recommended.
5) In patients with contraindications to immune checkpoint inhibitor therapy after first line chemotherapy, Docetaxel is recommended.
6) In patients with non-Squamous Cell Carcinoma who have not previously received Pemetrexed, Pemetrexed is recommended.
With sensitizing EGFR mutations:
1) In patients with disease progression after first line therapy with an EGFR Tyrosine Kinase Inhibitor (TKI) and the presence of the T790M resistance mutation, Osimertinib is recommended. If T790M mutation is not present, a platinum doublet is recommended.
2) In patients who received an EGFR-TKI in the first-line setting, had an initial response, and subsequently experienced slow or minimal disease progression at isolated sites, EGFR-TKI with local therapy to the isolated sites is an option.
With ROS1 rearrangement:
1) In patients who have not received prior Crizotinib, Crizotinib is recommended.
2) In patients who have received prior Crizotinib, platinum-based therapy in the second line with or without Bevacizumab is recommended.
With BRAF mutations:
1) In patients without prior immune checkpoint therapy and high PD-L1 expression (TPS more than 1%), single agent Atezolizumab, Nivolumab, or Pembrolizumab is recommended.
2) In patients who have received prior immune checkpoint therapy, Dabrafenib alone or in combination with Trametinib in third line, is an option.
Recommendations: Third Line Treatment for Patients
1) In patients without a tumor EGFR-sensitizing mutation or ALK or ROS1 gene rearrangement and with non-Squamous Cell Carcinoma and PS of 0 or 1 (and appropriate PS of 2), who received chemotherapy with or without Bevacizumab and immune checkpoint therapy, single agent Pemetrexed or Docetaxel are options.
2) In patients with tumor EGFR-sensitizing mutation(s) who have received at least one first-line EGFR-TKI and prior platinum-based chemotherapy, there are insufficient data to recommend immunotherapy in preference to chemotherapy.
Recommendations: Fourth Line Treatment for Patients
Patients and clinicians should consider and discuss experimental treatment, clinical trials, and continued best supportive (palliative) care.
Systemic Therapy for Stage IV Non-Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. Hanna N, Johnson D, Temin S, et al. J Clin Oncol 2017;35:3484-3515
