KEY TAKEAWAYS
- The CheckMate 7FL phase III trial aimed to evaluate nivolumab (immunotherapy) alongside standard chemo and hormone therapy for high-risk, early-stage ER+ BC.
- The primary endpoint was pCR. Secondary endpoints were pCR, RCB, AE, and death incidences.
- The result demonstrated that neoadjuvant treatment with NIVO + NACT significantly improved pCR and RCB 0–1 rates, particularly in PD-L1+ patients.
Early-stage, high-risk breast cancer(BC) with positive estrogen receptors and negative HER2 status often receives a two-step treatment approach: chemo before neoadjuvant chemotherapy (NACT) and hormone therapy after surgery (ET).
Researchers aimed to evaluate nivolumab(NIVO) (immunotherapy) alongside standard chemo and hormone therapy for high-risk, early-stage ER+ BC.
The study included newly diagnosed ER+ HER2− BC patients with stages T1c–2 and N1–2 or T3–4 and N0–2 of grade 2 (ER 1–10%) or 3 (ER ≥ 1%). Patients were randomly assigned 1:1 to receive NACT + NIVO 360 mg Q3W/NIVO 240 mg Q2W (arm A) or NACT + placebo(PBO) (arm B).
In April 2022, based on external data, the trial closed to new enrollment; the primary endpoint was amended only to include the pathological complete response (pCR; ypT0/is ypN0) rate in the modified intention-to-treat population (mITTP; database lock 14 Apr 2023).
Secondary endpoints included pCR rates in programmed death ligand 1 (PD-L1)-positive (PD-L1+) patients (SP142 ≥ 1%), residual cancer burden (RCB) 0–1 rates (all patients and PD-L1+), adverse event (AE) incidences, and death incidences.
Of 830 screened patients, 521 were randomized (arm A/B, n = 263/258), with 510 included in the mITTP population. Baseline characteristics were balanced between arms. The pCR rate was significantly higher in arm A (24.5%) compared to B (13.8%; P = 0.0021), particularly in the stage III subgroup (Arm A/B, 30.7%/8.1%). Nivolumab’s benefit on pCR was more pronounced in PD-L1+ patients (AD, 24.1%; 44.3% in arm A, 20.2% in arm B). RCB 0–1 rates improved overall, especially in PD-L1+ patients.
During the neoadjuvant chemotherapy phase, the incidence of grade 3/4 treatment-related adverse events (AEs) was similar across arms (arm A/B, n = 92[35%]/82[32%]). In arm A, two study-drug-related deaths occurred (pneumonitis, hepatitis), and the incidence of immune-mediated adverse events (IMAE) was higher in arm A compared to B.
The result demonstrated that neoadjuvant treatment with NIVO + NACT significantly improved pCR and RCB 0–1 rates, particularly in PD-L1+ patients.
Clinical Trial: https://clinicaltrials.gov/study/NCT04109066
Loi S, Curigliano G, Salgado RF, Romero Diaz RI, Delaloge S, Rojas C, Kok M, Saura Manich C, Harbeck N, Mittendorf EA, Yardley D, Pusztai L, Suarez Zaizar A, Ungureanu A, Ades F, Chandra R, Nathani R, Pacius M, Wu JQ, McArthur HL. A randomized, double-blind trial of nivolumab (NIVO) vs placebo (PBO) with neoadjuvant chemotherapy (NACT) followed by adjuvant endocrine therapy (ET) ± NIVO in patients (pts) with high-risk, ER+ HER2− primary breast cancer (BC). Ann Oncol. 2023;34(suppl_2):S1254-S1335. doi:10.1016/annonc/annonc1358.
