SAN DIEGO – Stereotactic ablative body radiotherapy (SABR) appeared to delay the need for changes in systemic therapy in postmenopausal patients with oligoprogressive luminal ER-positive, HER2-negative breast cancer, according to a new phase 2 study.
In the AVATAR trial, patients with one to five metastatic lesions who’d been treated with cyclin-dependent kinase (CDK) 4/6 inhibitors and aromatase inhibitors for at least 6 months underwent SABR. Of those, 47% had event-free survival of more than 6 months, an unexpectedly high figure, reported radiation oncologist Steven David, MBBS, of Peter MacCallum Cancer Center, Melbourne, and colleagues at the annual meeting of the American Society for Radiation Oncology.
“We found surprisingly that SABR delayed a change in therapy by 10 months, which is great for patients. Also, one in three patients had a second round of SABR,” said Dr. David in an interview. “This trial provides the first prospective evidence to delay a change in therapy in this population, and this strategy is ready to go now.”
According to Dr. David, oligoprogressive luminal, ER-positive, HER2-negative, advanced breast cancer cannot be cured. However, patients can live more than 10 years in some cases, and an early treatment – CDK 4/6 inhibitors and aromatase inhibitors – is well tolerated. “Patients can lead a normal life and avoid chemo” as long as those medications keep working.
The goal of the study was to determine if SABR is helpful in these patients. The treatment, which produces highly focused radiation, “has very few side effects and does a great job in eliminating progressing metastases,” Dr. David said.
For the study, researchers recruited 32 subjects at 13 Australian sites. Participants could not have had leptomeningeal disease, previous chemotherapy for metastatic disease, or prior radiotherapy to an oligoprogressing lesion. Most metastases were to bone (n = 44, 71%), node (systemic, n = 8; 13%) and lung (n = 4; 6%).
The patients were treated with SABR, most commonly 24 Gy (n = 25; 43%) and 20 Gy (n = 10; 17%); half had one lesion treated (50%), and 25% had two lesions treated.
The median follow-up was 15.8 months. The median event-free survival was 5.2 months (95% confidence interval, 3.1-9.4 months), with events defined as progression within 6 months or in at least three lesions. Fifteen patients (47%) reached event-free survival of 6 or more months.
Elysia Donovan, MD, MSc, a radiation oncologist at McMaster University, Hamilton, Ont., said in an interview that the new study is thoughtfully designed, although it’s not definitive. “At this point we still do not know the optimal treatment regimen for oligoprogressive breast cancer. The findings of this trial are promising and exciting. However, further randomized trials are required before routine implementation in clinical practice. For now, patients should be considered in a case by case basis with multidisciplinary discussion to determine the optimal systemic therapy regimen at oligoprogression and whether SABR may provide benefit.”
Median modified progression-free survival was 10.4 months, and median progression-free survival was 5.2 months; 31% of patients received SABR for further oligoprogression, and 46% patients remained on CDK4/6 inhibitors and aromatase inhibitors for 12 months. Overall survival was 100%.
A total of 14 patients had grade 1 adverse events, 2 had grade 2 events, and none had grade 3 or higher events; 47% had no treatment-related toxicity.
The strategy “potentially has a place in other cancer types and other breast cancer types,” Dr. David said.
In an interview, Katarzyna Jerzak, MD, MSc, a medical oncologist with Sunnybrook Odette Cancer Center in Toronto, said the findings are promising, although the study is small and the patients are similar. Toxicity was limited, and a 12-month delay in a switch to therapy – reached by 46% – “is very meaningful for patients.” She added that “the positive results should serve as motivation to investigate the strategy further.”
Dr. David said a larger trial called AVATAR 2 is funded and in the works. It will have more patients and more breast cancer subtypes.
The study was funded by the Donald Ratcliffe and Phyllis McLeod Trust. Dr. David disclosed grant/research funding from Roche Genentech, and other authors reported various disclosures including relationships with AstraZeneca, Pfizer, Gilead, and others. Dr. Jerzak disclosed speaker/advisor board/consultant relationships with Amgen, AstraZeneca, Apobiologix, Eli Lilly, Esai, Genomic Health, Gilead, Knight Therapeutics, Merck, Myriad Genetics, Pfizer, Roche, Seagen, and Novartis and research funding from AstraZeneca, Eli Lilly, and Seagen. Dr. Donovan disclosed a Bright Foundation grant for a prospective trial of SABR for oligoprogressive breast cancer.