|The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Adding durvalumab to neoadjuvant chemotherapy improved long-term survival outcomes in patients with triple-negative breast cancer (TNBC), according to results presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.1
Durvalumab was associated with survival benefits despite a small, nonsignificant increase in pathologic complete response (pCR) rate and no continuation of treatment with durvalumab after surgery, said Sibylle Loibl, MD, PhD, co-chair of the German Breast Group in Neu-Isenburg, Germany, when presenting these results at ASCO 2021.
The findings raise questions about the need for adjuvant therapy with checkpoint inhibitors in this setting, Dr Loibl said.
She presented results from the GeparNuevo trial (ClinicalTrials.gov Identifier: NCT02685059), a phase 2 study of 174 patients with TNBC who were randomly assigned to durvalumab or placebo.
Patients initially received durvalumab or placebo alone for 2 weeks. Then, they received durvalumab or placebo in combination with nab-paclitaxel for 12 weeks. After that, patients received standard epirubicin and cyclophosphamide, with either durvalumab or placebo, for 8 weeks. Finally, patients went on to surgery.
As previously reported2, the pCR rate was 53.4% with durvalumab and 44.2% with placebo, a difference that was not statistically significant (odds ratio [OR] 1.53; 95% CI, 0.82-2.84; P =.182).
In the update at ASCO 2021, Dr Loibl reported long-term outcomes, including invasive disease-free survival (iDFS), distant disease-free survival (DDFS), and overall survival (OS).
There were 62 patients in the durvalumab arm and 67 in the placebo arm who had undergone surgery and were evaluable for long-term outcomes.
At a median follow-up of 43.7 months, 34 iDFS events occurred — 12 in the durvalumab arm and 22 in the placebo arm. The 3-year iDFS rate was 85.6% with durvalumab and 77.2% with placebo (stratified hazard ratio [HR], 0.48; 95% CI, 0.24-0.97; P =.0398).
The 3-year DDFS rate was 91.7% with durvalumab and 78.4% with placebo (HR, 0.31; 95% CI, 0.13-0.74; P =.005). The 3-year OS rate was 95.2% and 83.5%, respectively (HR, 0.24; 95% CI, 0.08-0.72; P =.0108).
Overall, outcomes were superior in patients who had achieved a pCR, with significant differences seen in iDFS (P =.004), DDFS (P =.003), and OS (P =.012). Dr Loibl noted that patients who achieved a pCR appeared to have better survival outcomes with durvalumab than with placebo.
Although durvalumab added to neoadjuvant chemotherapy significantly improved survival outcomes in TNBC, Dr Loibl said the value of anti-PD-L1 therapy for long-term outcomes needs to be explored further.
“The pCR improvement with durvalumab was, at best, modest and requires further assessment of the association of pCR and long-term outcomes with checkpoint inhibitor therapies,” Dr Loibl said. “Given these results, the value of adjuvant therapy with a checkpoint inhibitor after surgery needs to be further assessed.”
Disclosures: This research was supported by GBG Forschungs GmbH (the German Breast Group), AstraZeneca, and Celgene. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Read more of Cancer Therapy Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.
- Loibl S, Schneeweiss A, Huober JB, et al. Durvalumab improves long-term outcome in TNBC: results from the phase II randomized GeparNUEVO study investigating neoadjuvant durvalumab in addition to an anthracycline/taxane based neoadjuvant chemotherapy in early triple-negative breast cancer (TNBC). J Clin Oncol. 2021;39:(suppl 15; abstr 506). doi:10.1200/JCO.2021.39.15_suppl.506
- Loibl S, Untch M, Burchardi N, et al. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. Ann Oncol. 2019;30(8):1279-1288. doi:10.1093/annonc/mdz158