SAN DIEGO—Consolidation therapy improved survival by 6 months in a group of advanced non-small cell lung cancer (NSCLC) patients with synchronous oligometastatic tumors, according to a study presented at the 2019 Multidisciplinary Thoracic Cancers Symposium (Abstract 1).
A retrospective analysis of patient records at MD Anderson Cancer Center showed that those who received comprehensive local consolidative therapy (LCT) to the primary tumor and all distant metastases had median survival of 29 months versus 23 months for patients who did not. Moreover, the difference remained the same after controlling for different patient characteristics, said Erin Corsini, MD, a clinical research fellow at the University of Texas MD Anderson Cancer Center in Houston.
“Advanced NSCLC is frequently present at diagnosis and has a dismal prognosis,” Corsini told a press briefing. “Although not all people with stage IV NSCLC are the same, there are treatment options for those with limited metastatic disease. However, treatment strategies consisting of aggressive local therapy represent an evolving paradigm for select patients with advanced non-small cell lung cancer who present with a limited burden of metastatic disease.”
The investigators found that patients treated with LCT to all sites had a 3-year overall survival rate of 42 percent and a 5-year rate of 32 percent. The best outcomes were in patients with stage I or II thoracic cancer adenocarcinoma, no bone metastases.
“In select populations of patients, local consolidative therapy to all sites of disease with surgery, radiation therapy, or a combination of the two appears to show promise in prolonging overall survival. Patients who seem to have gained the most benefit were those with more favorable disease characteristics, such as adenocarcinoma, early intrathoracic stage, and absence of bone metastases.”
Corsini and her colleagues at MD Anderson reviewed the records of 194 stage IV NSCLC patients seen at the cancer center between 2000 and 2017. Included were patients with 1-3 synchronous metastatic tumors. Intrathoracic nodal disease counted as one site, and 70 percent of the subjects had 2-3 distant metastases and almost 90 percent also received systemic therapy.
Consolidative treatment of the primary tumor was associated with improved control of local and regional recurrences, the team found, and the rate of locoregional progression was 21 percent for patients given LCT to the primary tumor, compared to 43 percent for other patients. It also trended toward an association with improved overall survival (p=0.08), although this was not the case with LCT to distant metastases (p=0.21).
Squamous histology, higher intrathoracic stage, and bone metastases were all associated with poorer survival. Several recent clinical trials have indicated that LCT might provide survival benefits, Corsini noted.
“Our results are not only consistent with, but arguably bolster, the previously reported findings. Taken together, these studies make a strong case for LCT in patients with oligometastatic NSCLC. As the evidence accumulates and we learn that there are options for patients with oligometastatic disease, it is important that providers, patients, and families discuss these possibilities and how they align with their goals and priorities for treatment.”
Methodology, Other Findings
The researchers first identified 194 NSCLC patients treated at the center for NSCLC and at least three synchronous metastatic lesions. Intrathoracic nodal disease counted as one site. The median age of patients was 62 years. A total of 75 percent of the subjects had adenocarcinoma and 70 percent had nonregional distant metastases at 2-3 sites. These included 44 percent with brain metastases, 26 percent bone, and 19 percent with adrenal tumors.
Ninety percent of the patients underwent systemic therapy, with LCT to the primary lesion used in 75 percent, to all distant metastases in 76 percent, and to all disease sites in 62 percent of the patients.
Locoregional progression rates were lower in patients treated with LCT to the primary tumor (21%) than those who did not (43%). At a median follow-up of 52.3 months, the median overall survival for all patients was 26.5 months.
Although metastatic disease site was not associated with prognosis, progression on first-line systemic therapy was associated with an increased in mortality (HR 1.87), while comprehensive LCT to all sites was associated with improved overall survival (HR 0.67). A similar trend toward improved survival was observed with receipt of LCT to the primary lesion (HR 0.71). In contrast, LCT to distant metastases was not associated with a survival benefit. On multivariable analysis, receipt of comprehensive LCT to all sites of disease (HR 0.68) as well as adenocarcinoma histology were independently associated with improved survival.
“These results support ongoing prospective efforts to fully characterize the therapeutic benefits associated with this management strategy,” Corsini noted.
“Comprehensive local consolidation was associated with durable, long-term survival, with 1- and 5-year survival rates approximating that which was historically observed in earlier stages of disease,” he told reporters. “Given our findings, we speculate that patients with adenocarcinoma, low intrathoracic disease burden, and absence of bone metastases constitute those patients most likely to drive durable survival benefit.”
Charles B. Simone, II, MD, Professor and Chief Medical Officer of the New York Proton Center, told Oncology Times that local therapy—either radiation therapy or surgery—is increasingly being used for patients with both oligometastatic disease and oligoprogressive disease, and is being considered as a standard treatment approach.
“With the increasing use of stereotactic body radiation therapy both for early-stage non-small cell lung cancer and for sites of metastatic non-small cell lung cancer, oncologists now have an effective tool that can maximize local control and more safely deliver tumoricidal irradiation doses,” he noted.
For NSCLC oligometastatic disease, several important randomized trials have recently been reported. These include a 2016 University of Texas MD Anderson Cancer Center-led multicenter trial published in Lancet Oncology (2016;17(12):1672-1682) and a University of Texas Southwestern Medical Center study published in 2018 in JAMA Oncology (2018;4(1):e173501), both of which showed that local consolidative radiotherapy tripled progression-free survival compared with systemic therapy alone.
Additionally, while not solely restricted to NSCLC patients, he pointed to data from the SABR-COMET trial, presented in the plenary session at the 2018 American Society for Radiation Oncology (ASTRO) Annual Meeting. That study showed a significant improvement in overall survival with stereotactic body radiation therapy compared with systemic therapy alone.
“With multiple randomized trials, such an aggressive local therapy approach for select metastatic patients is increasingly being considered a validated treatment approach.”
While clinical treatment guidelines are currently lacking, Simone noted that the definition of oligometastatic disease is the subject of a soon-to-be released ASTRO guideline. “This is eagerly awaited, and it will undoubtably ultimately spur an oligometastatic ASTRO guideline paper across multiple primary disease sites, including lung cancer,” he said. “Additionally, the American Radium Society and American College of Radiology Appropriate Use Criteria Guideline Committee is releasing a guideline paper specifically on oligometastic and oligoprogressive non-small cell lung cancer this year.”
Simone also discussed several areas where research is still needed: “The ASTRO definition paper will be of great value, but more work is still needed to understand which patients benefit the most from local consolidative therapy in oligometastatic disease. We need to better understand if patients with a single metastatic lesion versus two versus up to five lesions benefit equally. We also need to better understand how aggressive local therapy benefits patients with lung metastasis to the brain versus the liver versus the adrenal glands versus bones versus other sites.”
Lastly, he said that as oligometastatic studies reported to date have included patients receiving cytotoxic chemotherapy, better understanding is needed on how consolidative therapy impacts outcomes in patients receiving immunotherapy.
Many of these questions will be answered, in part, through the ongoing NRG Oncology LU;002 trial “Maintenance Systemic Therapy Versus Local Consolidative Therapy (LCT) Plus Maintenance Systemic Therapy For Limited Metastatic Non-Small Cell Lung Cancer (NSCLC): A Randomized Phase II/III Trial.”
Kurt Samson is a contributing writer.