ASCO Updates Advice on Drug Therapy for Advanced Lung Cancer

With all the recent advances in the drug treatment of lung cancer, most notably immunotherapy and targeted therapy, the American Society of Clinical Oncology (ASCO) has issued an update to its clinical practice guideline on advanced non–small cell lung cancer (NSCLC).

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

The last update was in 2015.

The latest update, published online August 14 in the Journal of Clinical Oncology, reflects changes in evidence since then, including with regard to immune checkpoint therapy and targeted therapy for patients whose NSCLC has epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or proto-oncogene receptor tyrosine kinase (ROS1) targets.

"It is important to update the non-small cell lung cancer guidelines due to the rapid evolution of treatment options as our understanding of the molecular biology and genetics of lung cancer continues through basic research, translational research, and clinical trials," Gregory Masters, MD, co-chair of the guideline expert panel, told Medscape Medical News.

"We have new treatment options available with targeted therapies and immunotherapy as well as standard chemotherapy options, and we want to make sure clinicians throughout the country have the help and support they need in recommending the most appropriate care for their patients with this increasingly complex disease. Giving our patients the best, personalized approach to their individual cancer can improve their quality of life and survival and help us use our limited resources most efficiently," added Dr Masters.

First-L ine Therapy in Patients Without Mutations

Regarding recommendations for first-line treatment for patients with non–squamous cell carcinoma or 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):

With high programmed cell death ligand 1 (PD-L1) expression (tumor proportion score [TPS] 50% or greater) and no contraindication, single-agent pembrolizumab (Keytruda, Merck) is recommended (evidence quality: high; strength of recommendation: strong).
With low PD-L1 expression (TPS < 50%), a variety of combination cytotoxic chemotherapies (with or without bevacizumab if patients are receiving carboplatin and paclitaxel) are recommended (platinum-based [evidence quality: high; strength of recommendation: strong]; non–platinum-based [evidence quality: intermediate; strength of recommendation: weak]).
All other clinical scenarios for first-line treatment follow 2015 recommendations.

Second-Line Therapy in Patients Without Mutations

Regarding recommendations for second-line treatment in patients 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):

In patients with high PD-L1 expression and no contraindications who received first-line chemotherapy, without prior immune checkpoint therapy, single-agent nivolumab (Opdivo, Bristol-Myers Squibb), pembrolizumab, or atezolizumab (Tecentriq, Genentech) is recommended (evidence quality: high; strength of recommendation: strong).
In patients with negative or unknown PD-L1 expression and no contraindication who received first-line chemotherapy, nivolumab, or atezolizumab, a variety of combination cytotoxic chemotherapies are recommended (evidence quality: high; strength of recommendation: strong).
Other checkpoint inhibitors, combination checkpoint inhibitors, and immune checkpoint therapy with chemotherapy are not recommended.
In patients who received an immune checkpoint inhibitor as first-line therapy, a variety of combination cytotoxic chemotherapies are recommended (platinum-based [evidence quality: high; strength of recommendation: strong]; non–platinum-based [informal consensus; evidence quality: low; strength of recommendation: strong]).
In patients with contraindications to immune checkpoint inhibitor therapy after first-line chemotherapy, docetaxel is recommended (evidence quality: intermediate; strength of recommendation: moderate).
In patients with non–squamous cell carcinoma who have not previously received pemetrexed (Alimta, Lilly), pemetrexed is recommended (evidence quality: intermediate; strength of recommendation: moderate).

**Patients With Sensitizing EGFR Mutations**

With disease progression after first-line EGFR tyrosine kinase inhibitor (TKI) therapy and a T790M mutation, osimertinib (Tagrisso, AstraZeneca) is recommended (evidence quality: high; strength of recommendation: strong).
If the tumor lacks the T790M mutation, a platinum doublet is recommended (informal consensus; evidence quality: low; strength of recommendation: strong).
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 (informal consensus; evidence quality: insufficient; strength of recommendation: weak).

**Patients With ROS1 Rearrangement**

In patients who have not received prior crizotinib (Xalkori, Pfizer), crizotinib is recommended (informal consensus; evidence quality: low; strength of recommendation: moderate).
In patients who have received prior crizotinib, platinum-based therapy in the second line with or without bevacizumab (Avastin, Genentech) is recommended (informal consensus; evidence quality: insufficient; strength of recommendation: moderate).

**Patients With BRAF Mutations**

In patients without prior immune checkpoint therapy and high PD-L1 expression, atezolizumab, nivolumab, or pembrolizumab is recommended (informal consensus; evidence quality: insufficient; strength of recommendation: weak).
In patients who have received prior immune checkpoint therapy, dabrafenib (Tafinlar, Novartis) alone or in combination with trametinib (Mekinist, Novartis) as third line is an option (informal consensus; evidence quality: insufficient; strength of recommendation: moderate).

Third-Line Therapy Recommendations

In patients without a tumor EGFR-sensitizing mutation or ALK or ROS1 gene rearrangement and with non–squamous cell carcinoma and a 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 (informal consensus; evidence quality: low; strength of recommendation: strong).
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 (pemetrexed or docetaxel [informal consensus; evidence quality: insufficient; strength of recommendation: weak]).

For fourth-line treatment, ASCO advises patients and clinicians to consider and discuss experimental treatment, clinical trials, and continued best supportive (palliative) care.

"For all recommendations, benefits outweigh harms," the ASCO expert panel notes.

Disclosures provided by guideline writers are available online at www.jco.org

J Clin Oncol. Published online August 14, 2017. Full text

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