SAN DIEGO — In patients with breast cancer who have undergone a mastectomy, hypofractionated radiation therapy (HFRT) delivered in fewer fractions over a shorter period was not inferior to conventional fractionated radiation therapy (CFRT) and appears to have similar toxicity.
The new findings, from a large randomized trial involving 820 women, were presented here during a plenary session at the American Society for Radiation Oncology (ASTRO) 2017 Annual Meeting.
At 5 years, the results confirmed that hypofractionated approach, which delivered 43.5 Gy in 15 fractions over 3 weeks, had efficacy and toxicity similar to those of the conventional approach, which delivers 50 Gy in 25 fractions over 5 weeks.
The 5-year rate of locoregional recurrence was 8.3% for patients who received HFRT and 8.1% for CFTR (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.67 – 1.83),
“This is the first large, well-conducted randomized trial to demonstrate conclusively that hypofractionated radiation therapy to nodal regions in breast cancer patients is safe and effective in the postmastectomy setting,” said study author Shulian Wang, MD, a radiation oncologist at the Chinese Academy of Medical Sciences in Beijing.
“It shortens treatment time, saves medical resources, reduces medical cost, and makes radiation therapy more convenient for the patient,” Dr Wang noted.
She explained that in China, where the study was conducted, radiation therapy after mastectomy is underused because of such factors as a lack of radiation therapy facilities and cost. Only 52% of patients with stage III disease receive radiation therapy despite evidence that CFRT, at 50 Gy delivered in 25 fractions over 5 weeks, to the chest wall and nodal regions can improve outcomes in high-risk patients.
However, US experts commenting on the new results pointed out that women in this trial had not undergone breast reconstruction, and this important issue is being addressed in an ongoing US trial.
Noninferior to Standard Treatment
Previous randomized trials of HFRT after breast-conserving surgery in patients with early breast cancer have reported results similar to those with CFRT. However, Dr Wang noted that level I efficacy evidence for HFRT after mastectomy is lacking.
Hence, she and her colleagues conducted a phase 3 noninferior randomized trial.
A cohort of 820 high-risk patients with breast cancer (94.6% with stage III and 5.4% with stage II disease) were randomly assigned to receive HFRT (43.5 Gy in 15 fractions for 3 weeks or CFRT (50 Gy in 25 fractions for 5 weeks) to the chest wall and supraclavicular nodal region after mastectomy.
All patients in the cohort also received chemotherapy (88.6% taxanes and anthracycline, 8.9% taxane-based, 1.9% anthracycline-based, and 0.6% unknown). In addition, 16.8% received trastuzumab and/or hormonal therapy (76.5% of all patients; 94.5% of those eligible).
The study’s primary endpoint was locoregional recurrence, and median follow-up for surviving patients was 55 months.
The 5-year cumulative incidence of locoregional recurrence was 92.8% for the cohort, while the 5-year overall survival rate was 84.4% and the disease-free survival rate was 72.7%.
HFRT offered efficacy similar to that of CFRT. The 5-year overall survival rates were 83.2% for HFRT and 85.6% for standard treatment (HR, 1.13; 95% CI, 0.78 – 1.62).
Other measures of efficacy were also similar in the two groups: The 5-year disease-free survival rates were 74.6% and 70.7% (HR, 0.88; 95% CI, 0.67 – 1.16), and the 5-year rates for distant metastases were 23.2% and 26.2% (HR, 0.90; 95% CI, 0.67 – 1.20).
Toxicity was similar between the two groups, and there were no differences in radiation pneumonitis, late skin toxicity, lymphedema, and brachial plexopathy. No grade 4 or 5 toxicities were reported in either treatment group.
However, one difference was that patients receiving HFRT experienced less grade 3 acute skin toxicity (3.5% vs 7.8%; P = .008).
Data Needed for Reconstruction
In a discussion of the paper, Gary Freedman, MD, a professor of radiation oncology at the Hospital of the University of Pennsylvania, Philadelphia, noted that hypofractionation has been found to be just as effective as conventional therapy when used in the setting of breast-conserving surgery.
“But what about postmastectomy?” he asked, adding that the current study is “the end of the beginning for this question. This is a very large trial, there is 5-year data, and it takes us back to the year 2007-2008, when we were first getting phase 3 data in the postlumpectomy setting.”
Given this result, what does this mean for clinical practice?
Dr Freedman noted that hypofractionation “will not be an easier sell in the United States” in the postmastectomy setting.
“As compared to postlumpectomy, the stakes are higher,” he explained. “We are also concerned with reconstruction.”
The cohort in this study did not include women who had undergone reconstruction, and in fact, it was a contraindication, so data will be needed on that issue, he said.
And that is an important issue, Dr Freedman pointed out. “Reconstruction is expensive, and women spend a lot of money to have an excellent cosmetic result, so if we’re going to save money on hypofractionation, we want to make sure that we are not being pennywise and pound foolish in the long run.”
The number of potential complications can quickly change the paradigm for cost, he noted. “Patients and their referring plastic surgeons need to know that hypofractionation will not impose added risk to reconstruction.”
That is the main rationale for the upcoming Alliance trial, which will open enrollment in the United States within the next 6 months. Dr Freedman explained that this is a large randomized trial of over 800 women looking at hypofractionation after mastectomy and specifically after breast reconstruction. The primary endpoint will be reconstruction complications.
But for now, “I think it is suitable to use hypofractionation in women without reconstruction and for whom a 5-year result is sufficient,” he concluded. “Just like in the year 2008 when we very cautiously using hypofractionation in women who were older or who had other comorbidities.”
May Be Option for Some
Also weighing in on the study, Robert Mutter, MD, a consultant in the Department of Radiation Oncology at the Mayo Clinic, Rochester, Minnesota, also emphasized the importance of the upcoming Alliance trial, which will help define the role of hypofractionation in the postmastectomy setting.
Some data show a lower risk for complications with hypofractionation in women who have had breast-conserving surgery, Dr Mutter told Medscape Medical News.
“This may be the case for postmastectomy, but we don’t know that yet,” he said. “This is the first big randomized trial to ask those questions — is it safe and effective?”
Dr Mutter pointed out that even though the study was quite large, it was conducted in a single institution. “Still, it is very promising and this could be a wave of the future, but we need more data,” he said. “But for right now, it is a reasonable option for patients who may have difficulty getting the full 25 fractions and not undergoing immediate reconstruction. It seems to be safe and effective.”
Dr Wang and Dr Mutter have disclosed no relevant financial relationships. Two of the study investigators are employees of the Cancer Hospital & Institute. Dr Freedman received travel expenses from ABR.
American Society for Radiation Oncology (ASTRO) 2017 Annual Meeting. Abstract 5. Presented September 25, 2017.
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