Excitement Grows About Immunotherapy Potential in Breast Cancer

Andrew D. Smith
Published: Saturday, Mar 09, 2019

Hope Rugo, MD

Hope Rugo, MD

Although the first checkpoint inhibitor has just been approved for patients with breast cancer, findings from dozens of ongoing studies may eventually change the paradigm for large subsets of those with the malignancy. Two leading experts in the field, Hope S. Rugo, MD, FASCO, and Elizabeth Mittendorf, MD, PhD, discussed emerging trial data and the populations who might benefit the most from this modality during the 36th Annual Miami Breast Cancer Conference® (MBCC).

The prospects for administering these therapies moved from the realm of pending trials into clinical practice with the FDA’s approval Friday of atezolizumab (Tecentriq) for patients with metastatic triple-negative breast cancer (TNBC). The PD-L1 inhibitor is approved in combination with nab-paclitaxel (Abraxane) for patients with unresectable locally advanced or metastatic PD-L1–positive TNBC.

“The approval of atezolizumab for breast cancer is really important because we have our first approved checkpoint inhibitor, or really immune agonoist for the treatment of breast cancer,” Rugo, an MBCC co-chair who was among the principal investigators in the study, said in an interview. “Now our big challenge is to try and figure out how to expand the use of this class of drugs to other patients and with other chemotherapy combinations.”

Mittendorf echoed those sentiments. “It’s obviously a tremendously exciting day but also a tremendously exciting time,” she said in an interview. “It’s going to be a very fast-paced time…Of course, triple negative is just 1 subtype of breast cancer and so there’s going to be tremendous enthusiasm for continuing to explore opportunities to make our other tumor types susceptible to immunotherapy as well.”

She said the next steps in the research include determining which patients are likely to respond beyond the PD-L1–positive group, how those without PD-L1–positive expression on immune cell infiltrates will be treated, and what subsequent therapies should be administered to PD-L1–positive patients who initially respond and then progress.

The atezolizumab combination was approved based on findings from the phase III IMpassion 130 study (NCT0242589), which randomized 902 patients with untreated metastatic TNBC to nab-paclitaxel with either atezolizumab or placebo. Patients must test positive for PD-L1 expression. The FDA designated the VENTANA PD-L1 SP142 assay, which was used in the study, as a companion diagnostic for the atezolizumab combination.

In the intent-to-treat population, median progression-free survival (PFS) was 7.2 months with the atezolizumab combination and 5.5 months among those who received nab-paclitaxel plus placebo (hazard ratio [HR] for progression or death, 0.80; 95% CI, 0.69-0.92; P =.002).1 Median overall survival (OS) was 21.3 months with the atezolizumab regimen and 17.6 months with nab-paclitaxel alone (HR for death, 0.84; 95% CI, 0.69-1.02; P = .08).

For patients with PD-L1–positive tumors, the median PFS was 7.5 months with atezolizumab and 5.0 months with nab-paclitaxel alone (HR, 0.62; 95% CI, 0.49-0.78; P <.001). Median OS was 25.0 months and 15.5 months, respectively (HR, 0.62; 95% CI, 0.45-0.86). Positivity was defined as PD-L1 expression on tumor-infiltrating immune cells as a percentage of tumor area, with <1% categorized as negative and ≥1% as positive.1 Rugo said the OS findings are an interim result based on 60% of the events, but that the trend would likely be maintained when the data are updated later this year.

Even at this juncture, however, the OS benefit for the combination “is the amazing part of this data,” she said. “A 9.5-month difference—it’s unequaled. We haven’t seen it anywhere else,” Rugo noted. “It tells us 2 things: 1 is we can change the survival in patients with metastatic triple-negative breast cancer who have immune cells positive for PD-L1. It also tells us we can change the environment of the cancer to change its responsivness to treatment so that other treatments have to be working better.”

The rationale for using immune checkpoint inhibitors as neoadjuvant therapy also is growing. “Over the last few years, we have come to understand that more aggressive forms of breast cancer have some degree of host immunity, and as those tumors progress and become more resistant, the host immunity tends to decrease. As the tumor becomes more resistant, it also is able to reduce the body’s immune response to the cancer,” Rugo said in an earlier interview.

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