There was a small increase in pCR initially (with no continuity after surgery), questioning the need to maintain immunotherapy as adjuvant treatment, according to data presented in ASCO 2021
During ASCO World Congress 2021, the results of GeparNUEVO (NCT02685059), a randomized, phase II trial investigating the neoadjuvant use of durvalumab combined with anthracycline and taxane-based chemotherapy in early triple-negative breast cancer (TNBC) treatment, were presented.
The trial randomized patients with TNBC cT1b-cT4a-d to durvalumab 1.5g EV or placebo every four weeks. Durvalumab or placebo (750mg EV) in monotherapy were administered during the first two weeks (“window” phase), followed by durvalumab or placebo associated with nab-paclitaxel 125mg/m² weekly for 12 weeks, and finally, durvalumab or placebo plus epirubicin/cyclophosphamide every two weeks for four cycles. Randomization was stratified by stromal tumor-infiltrating lymphocytes (sTILs) (low [≤10%], intermediate [11-59%], high [≥60%]). The main endpoint was to evaluate the rate of pathologic complete response rate (pCR, defined by ypT0 ypN0). Secondary endpoints were invasive disease-free survival (iDFS), distant disease-free survival (dDFS), and overall survival (OS).
In total, 174 patients were enrolled between June 2016 and September 2017. The pCR rate with durvalumab was 53.4% versus 44.2% for placebo (OR 1.45; 95% CI 0.80–2.63; p = 0.224). The effect of durvalumab for the primary endpoint was observed only in the window phase (pCR 61.0% versus 41.4%; OR 2.22; 95% CI 1.06–4.64; p = 0.035; interaction p = 0.048).
After a mean follow-up of 42.2 months, 34 events occurred in 174 patients. The iDFS at three years in patients with pCR versus without pCR was 92.0% versus 71.9% (log-rank p = 0.002). iDFS at three years was 84.9% with durvalumab versus 76.9% with placebo (HR 0.54; CI 95% 0.27-1.09; stratified log-rank p = 0.0559). The dDFS at three years was 91.4% versus 79.5% (HR 0.37; 95% CI 0.15-0.87; p = 0.0148). Finally, The OS at three years was 95.1% versus 83.1% (HR 0.26; 95% CI 0.09-0.79; p = 0.0076). No difference was observed for iDFS, dDFS, and OS between the window and the non-window cohort.
The researchers conclude that durvalumab added to neoadjuvant chemotherapy on TNBC significantly improved the long-term outcome, despite a small increase in pCR initially (with no continuity after surgery), questioning the need to maintain immunotherapy as adjuvant treatment.