CHICAGO – Women with breast cancer treated with neoadjuvant chemotherapy and surgery are more likely to have a recurrence in the breast, chest wall, or axilla or to die if they don’t receive adjuvant radiation therapy, even if they had a pathologic complete response to the chemotherapy, new data show.

In a meta-analysis of three Gepar trials conducted by the German Breast Group, radiation therapy was associated with a 38% lower multivariate risk of locoregional recurrence or death, investigators reported at the annual meeting of the American Society of Clinical Oncology. Significant benefit was seen regardless of pathologic complete response, although findings across other subgroups were not consistent, possibly due to selection bias or underlying confounders.

“Radiotherapy is an independent prognostic factor for locoregional recurrence–free survival after neoadjuvant chemotherapy in breast cancer. However, the optimal selection criteria remain unclear,” commented first author Dr. David Krug of University Hospital Heidelberg (Germany).

“We are eagerly awaiting the results of prospective studies that are currently recruiting patients,” he added, referring to the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-51 trial and the Radiotherapy After Primary Chemotherapy for Breast Cancer (RAPCHEM) trial.

Findings of this meta-analysis are not practice changing, according to invited discussant Dr. Monica Morrow, chief of the breast service, department of surgery, and the Anne Burnett Windfohr Chair of Clinical Oncology at the Memorial Sloan Kettering Cancer Center in New York. “The Gepar data is not consistent enough across subsets to draw any different conclusions other than we need more data,” she said.

Focusing on the women who underwent mastectomy, she noted that only a small number who had a pathologic complete response did not receive radiation therapy, “so this study unfortunately lacks the power to tell us anything about the ability to eliminate radiation in this group.”

“What we’d really like to know about local control after neoadjuvant therapy is what’s the relative contribution of pretreatment stage and posttreatment stage to the risk of locoregional recurrence, especially in patients who achieve pathologic complete response? And if we try to address that question with this study, the results were a little murky,” Dr. Morrow further noted. For example, patients with higher–T stage primary tumors benefited from postmastectomy radiation, but patients who were clinically node positive did not.

“I think right now, what we have to say is we need to continue to do what we have been doing up until the present time, namely, patients whose presenting stage clearly indicates the need for radiotherapy should receive it, and patients who have lower-stage disease perhaps not,” she concluded, agreeing that the NSABP B-51 trial should help put this issue to rest.

Dr. Krug and his colleagues performed a pooled meta-analysis of data from the GeparTrio, GeparQuattro, and GeparQuinto trials of neoadjuvant chemotherapy, in which guidelines specified when adjuvant radiation therapy should be used. Those guidelines called for whole-breast radiation therapy with a boost after breast-conserving surgery (with omission of the boost in low-risk patients); radiation therapy after mastectomy for patients having more extensive disease before neoadjuvant chemotherapy; and radiation therapy for those with greater involvement of the regional lymphatics.

The meta-analysis was based on a total of 3,370 women. Overall, 94% received radiation therapy (99% of those who had undergone breast-conserving surgery and 85% of those who had undergone mastectomy).

With a median follow-up of 4.2 years, the 5-year rate of locoregional recurrence–free survival was 89.2% in the entire study population, according to Dr. Krug.

Women who did not receive radiation therapy had a significantly elevated risk of such recurrence or death compared with peers who received it. In subgroups analyses, benefit was significant whether women had had a pathologic complete response to neoadjuvant chemotherapy or not. Greatest absolute benefit was seen in those with a pathologic complete response, clinically positive nodes, or pathologically negative nodes.

The 5-year rate of disease-free survival was 74.0% in the entire study population. Here, there was only a trend toward a higher risk of events for women who did not receive radiation therapy.

In multivariate analyses, radiation therapy independently predicted better locoregional recurrence–free survival (hazard ratio, 0.62; P = .038) but not disease-free survival.

When analyses were restricted to women who had undergone mastectomy, radiation therapy was associated with significantly better locoregional recurrence–free survival among those with clinical stage T3/4 disease, pathologically negative nodes, a conversion from clinically positive to pathologically negative nodes, or hormone receptor–negative, HER2-positive disease.

It was associated with poorer disease-free survival for patients who did not achieve a pathologic complete response, had clinical stage T1/2 disease, or were clinically node negative.

Multivariate analysis here again showed that radiation therapy independently predicted better locoregional recurrence–free survival (HR, 0.56; P = .029) but not disease-free survival.

ASCO: Omitting adjuvant radiation after pCR ups locoregional recurrence risk