Findings from the randomized phase II CURB trial indicate that using stereotactic body radiation therapy to target oligoprogression in patients with non–small cell lung cancer significantly prolongs progression-free survival compared with standard systemic treatment. However, the same approach does not benefit patients with breast cancer.

For patients whose non–small cell lung cancer (NSCLC) has spread, but not extensively, after first-line therapy, targeting their few metastases with high-dose radiation may extend progression-free survival (PFS). This finding from CURB, a phase II trial at Memorial Sloan Kettering Cancer Center (MSKCC) in New York, NY, supports treating oligoprogression through localized rather than systemic means.

Broadly, cancers defined as oligoprogressive have limited sites of metastasis—up to five on average—that exhibit a mixed response to systemic therapy, “with some tumors starting to develop resistance, and others still under control,” explained lead investigator C. Jillian Tsai, MD, PhD. “We wanted to see if adding local radiation to specifically target progressing lesions could prolong disease stability.” She presented CURB's results at the 2021 American Society for Radiation Oncology Annual Meeting in Chicago, IL, October 24–27.

Study discussant Steven Chmura, MD, PhD, of the University of Chicago, observed that “we've learned metastasis is really a wide spectrum” in terms of lesion number and how slowly or quickly spread occurs. As such, “I think subsets of patients could potentially benefit from ablative techniques, if properly integrated” with standard therapy.

CURB enrolled 106 patients in two cohorts: 59 with NSCLC and 47 with breast cancer. All had five or fewer oligoprogressive sites. They were randomly assigned to receive either stereotactic body radiation therapy (SBRT)—which ensures highly focused delivery with minimal damage to surrounding tissue—followed by standard care or standard care alone.

In the NSCLC group, the median PFS for patients treated with SBRT was 44 weeks compared with 9 weeks for those given only standard therapy. However, among patients with breast cancer, SBRT did not significantly prolong PFS (18 vs. 19 weeks).

Zofia Piotrowska, MD, of Massachusetts General Hospital Cancer Center in Boston, noted that irradiating limited metastases is becoming routine in NSCLC, “but most commonly for one or two progressing lesions. It's difficult to know where to draw the line on what number constitutes oligoprogression and merits local treatment, versus switching to a different systemic therapy.” That said, regarding CURB, “the PFS difference with SBRT in lung cancer is quite impressive,” she added. “This is why we need such prospective studies, and preferably larger trials, so we can better determine if patients with more than just a couple of progressing sites still do well with radiation.”

Many of CURB's patients received SBRT for lesions in the lungs, which could cause pneumonitis, Piotrowska said. However, the investigators reported that this side effect and others associated with radiation, such as gastroesophageal reflux and diarrhea, were rare, “which is reassuring.”

Nikhil Wagle, MD, of Dana-Farber Cancer Institute, also in Boston, found it “particularly striking that there was such a discrepancy between breast cancer and lung cancer” regarding SBRT's potential to improve PFS. Perhaps, he said, “oligoprogressive lesions in breast cancer aren't as radiosensitive, nor do they represent the whole picture—there could be micrometastases that are growing but simply not discernible.” As well, although participants had all developed disease progression on first-line treatment, “maybe resistance to endocrine therapy or CDK4/6 inhibitors is somehow different” than to NSCLC drugs, and this could have impacted the negative results in CURB's breast cancer cohort.

To figure out the key differences, Tsai and her colleagues at MSKCC are carrying out exploratory analyses of circulating tumor cells and DNA from patients' blood samples. Meanwhile, other similar trials, such as HALT in the UK and STOP in Canada, are also under way.

“Hopefully these yield molecular markers down the road to help us understand who may benefit, or not” from localized treatment for oligoprogression, Wagle said. “Clearly there's distinct biology involved, which merits further investigation.” –Alissa Poh

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