Background: Hormone receptor-positive (HR+)/humaal growth factor receptor 2-negative (HER2-) breast cancer, the most common breast cancer type, has variable prognosis and high recurrence risk. Neoadjuvant therapy is recommended for median-high risk HR+/HER2- patients. This phase II, single-arm, prospective study aimed to explore appropriate neoadjuvant treatment strategies for HR+/HER2- breast cancer patients.
Methods: Eligible female patients with newly diagnosed, untreated HR+/HER2- breast cancer received 2 cycles of nab-paclitaxel and carboplatin (nabPCb). Magnetic resonance imaging (MRI) was performed to assess tumor responses, and ≥40% regression of the maximal tumor diameter was deemed chemo-sensitive. Chemo-sensitive patients continued nabPCb for 4 more cycles (group A). Chemo-insensitive patients were randomized to groups B, C, and D at a ratio of 1:3:1 to receive a new chemotherapy for 4 cycles or endocrine-immune-based therapy (dalpiciclib, letrozole and adebrelimab, with goserelin if patients were premenopausal) for 4 cycles or to undergo surgery. Peripheral blood and core-needle biopsy (CNB) samples were collected before treatment, followed by a next-generation sequencing (NGS) panel detection and similarity network fusion (SNF) typing through digital pathology data. The primary endpoint was the pathological complete response (pCR) rate, and the secondary endpoint was the clinical objective response rate (ORR).
Results: A total of 121 patients were enrolled (67.8% with stage III disease), with 76, 9, 27, and 9 patients in groups A, B, C and D, respectively. The total pCR rate was 4.1%, and all patients who received pCR were in group A. Group C had a better ORR than Group B (81.5% vs. 66.7%). Exploratory analysis revealed that patients with the SNF4 subtype were the most sensitive to nabPCb (pCR rate of 21.1% vs. 1.8% in group A), whereas patients in group C with the SNF2 subtype were more sensitive to endocrine-immune-based therapy (Miller-Payne grade 4-5, 45.5% vs. 6.3%).
Conclusions: Converting to endocrine-immune-based therapy improved the ORR, but not the pCR rate in chemo-insensitive patients. Neoadjuvant chemotherapy and endocrine therapy are not mutually exclusive. The SNF4 subtype of HR+/HER2- breast cancer was more chemo-sensitive, whereas the SNF2 subtype might be more sensitive to immunotherapy.
Background: The prognosis for non-small cell lung cancer (NSCLC) patients treated with standard platinum-based chemotherapy was suboptimal, with safety concerns. Following encouraging results from a preliminary phase I study, this phase II trial investigated the efficacy and safety of first-line sintilimab and anlotinib in metastatic NSCLC.
Methods: In this open-label, randomized controlled trial (NCT04124731), metastatic NSCLC without epithelial growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or proto-oncogene tyrosine-protein kinase ROS (ROS1) mutations, and previous treatments for metastatic disease were enrolled. Participants were randomly assigned in a 1:1 ratio to either sintilimab (200 mg every 3 weeks) plus anlotinib (12 mg D1-14 every 3 weeks) or a standard platinum-based chemotherapy regimen. Patients in the chemotherapy group were permitted to switch to sintilimab after disease progression. The primary endpoint was the objective response rate (ORR).
Results: From November 2019 to March 2023, 99 patients were randomized into the sintilimab plus anlotinib group (n = 49) and the chemotherapy group (n = 50). The ORR was significantly higher in the sintilimab plus anlotinib group (44.9%; 95% confidence interval [CI] = 30.7%-59.8%) compared to the chemotherapy group (18.0%; 95% CI = 8.6%-31.4%, P = 0.003). Progression-free survival (PFS) was also notably longer (median: 14.4 vs. 5.6 months; hazard ratio [HR] = 0.39; 95% CI = 0.23-0.67; P < 0.001). The 24-month overall survival rate was 58.4% (95% CI = 40.4%-72.6%) and 43.2% (95% CI = 26.0%-59.2%), respectively. The rate of grade 3 or higher treatment-related adverse events was lower in the sintilimab plus anlotinib group (28.0%) than in the chemotherapy group (49.0%), especially for the hematological toxicities.
Conclusion: First-line sintilimab plus anlotinib showed improved ORR and PFS, alongside a superior safety profile, compared to the standard platinum-based chemotherapy for metastatic NSCLC patients.
Background: The standard first-line treatment for human epidermal growth factor receptor 2 (HER2)-positive recurrent/metastatic breast cancer currently includes pertuzumab plus trastuzumab and docetaxel. This study aimed to evaluate the effectiveness of KN026, an anti-HER2 bispecific antibody, plus docetaxel in first-line treatment of HER2-positive recurrent/metastatic breast cancer.
Methods: This open-label, single-arm, phase II study enrolled patients with HER2-positive recurrent/metastatic breast cancer in 19 centers across China from December 30, 2019 to May 27, 2021. Patients were administered KN026 (30 mg/kg) plus docetaxel (75 mg/m2) in 21-day cycles. Primary endpoints included the objective response rate (ORR) and duration of response (DOR). In addition, overall survival (OS), progression-free survival (PFS), clinical benefit rate (CBR) and safety profile were examined.
Results: A total of 57 patients were included. In the efficacy analysis set of 55 patients, the ORR was 76.4% (95% confidence interval [CI], 63.0%-86.8%), and the CBR was 85.5% (95% CI, 73.3%-93.5%). The median DOR was not reached (95% CI, 20.7 months-not reached). In the safety set of 57 patients, the median PFS was 27.7 months (95% CI, 18.0 months-not reached). The median OS was not reached, with OS rates at 12, 24 and 30 months of 93.0%, 84.1% and 78.5%, respectively. Grade ≥3 treatment-emergent adverse events (AEs) were detected in 36 (63.2%) patients. No deaths were attributed to KN026 or docetaxel.
Conclusion: KN026 plus docetaxel showed promising efficacy and a manageable safety profile in first-line treatment of HER2-positive recurrent/metastatic breast cancer.