Combination approach appears best in advanced lung cancer

By David Douglas

NEW YORK (Reuters Health) - 30/8/2019

In patients with stage-IV non-small-cell lung cancer (NSLCC), systemic therapy by itself appears less effective in reducing mortality risk than when it's used with other treatment modalities, according to a retrospective study.

"Systemic therapy is the cornerstone for treatment for patients with stage-IV disease," said Dr. Hyun S. Kim of Yale School of Medicine, in New Haven, Connecticut. However, Dr. Kim told Reuters Health by email, his team's findings show that the "combination of local treatments (surgery, radiation and/or thermal ablation) and systemic therapy versus systemic therapy alone showed survival benefits."

The researchers analyzed 2010-2015 data from the National Cancer Database on close to 35,000 patients, with a median age of 68 years. Of these, 24,513 received systemic therapy alone, 9,539 had external beam radiotherapy (EBRT) or thermal ablation (TA) plus systemic therapy and 835 underwent surgical resection plus systemic therapy.

Follow-up lasted a median of 39.4 months, Dr. Kim and his colleagues report in JAMA Network Open, online August 21.

After adjustment, surgical resection was associated with significantly superior overall survival compared with EBRT/TA (hazard ratio, 0.62). This was also the case compared with systemic therapy alone (HR, 0.59).

Patients treated with EBRT/TA also had significantly better overall survival than those given systemic therapy alone (HR, 0.95).

In further analysis, compared with systemic therapy alone, the higher survival associated with EBRT/TA "was especially pronounced in stage IV squamous cell carcinoma with limited T and N category disease and oligometastases (HR, 0.68)," with an overall survival rate at one year of 60.4% versus 45.4% and, at three years, 20.2% versus 10.6%.

However, patients with adenocarcinoma, T3 to T4 category disease, N2 to N3 category disease, and two or more distant metastatic sites had significantly worse overall survival after EBRT/TA compared with systemic therapy alone (HR, 1.39).

"As many as 55% of patients with non-small-cell lung cancer present with stage-IV disease at diagnosis," noted Dr. Kim He and his colleagues say "future studies are warranted to assess the combination therapies and sequencing of systemic and local therapies in stage IV NSCLC."

Dr. Abbas Abbas of Fox Chase Cancer Center, in Philadelphia, told Reuters Health by email, "The vast majority of (patients with metastases) are offered only systemic treatment with chemotherapy and/or immunotherapy and are usually not considered for local treatment such as surgical removal or ablation."

However, in the current study, the researchers "found that patients who had surgical removal of metastatic disease showed the best overall survival compared to the other 2 groups. Patients who had systemic therapy plus ablation had less favorable outcomes than the surgical group but still significantly better than those who underwent only systemic therapy."

"Of course, not all patients with stage-IV lung cancer are candidates for local treatment," added Dr. Abbas, who is chief of the division of cancer surgery. "This is only feasible in situations with a small number of metastatic lesions, also called oligometastatic disease. However, this study along with several other previous ones continues to show that an aggressive approach to eradicating metastatic disease can often translate to better outcomes."


JAMA Netw Open 2019.

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