4520 Background: RC48-ADC (Disitamab Vedotin) is a novel humanized anti-HER2 antibody-drug conjugate (ADC). RC48-ADC demonstrated a promising efficacy with a manageable safety profile in HER2-positive locally advanced or metastatic UC patients who failed to platinum based chemotherapy in RC48-C005 and RC48-C009 trials. Here are the pooled results of the two studies with the supplementary efficacy, safety and updated OS data. Methods: Both of the two trials are single-arm, multi-center, phase II trials. Eligible patients were 18̃80 years old, with central-laboratory confirmed, histologically HER2-postive (IHC2+,3+), unresectable mUC. Patients had at least one line of systemic chemotherapy. The primary endpoint was objective response rate (ORR). Progress-free survival (PFS), overall survival (OS), and safety were also assessed. Results: RC48-C005 and RC48-C009 enrolled HER2-positive locally advanced or metastatic UC patients from Nov 2017 to Sep 2020. 107 mUC patients (80 males; median age 63 y [40-79]) were enrolled. 64.5% patients had received ≥ 2 lines systemic chemotherapy. 90.7% patients had visceral metastases. As of 04 Sep 2021 (data cutoff), The overall confirmed ORR as assessed by the BIRC was 50.5% (95% CI: 40.6%, 60.3%). Similar responses were observed in prespecified subgroups. cORR was 52.1% (25/48) for patients with liver metastasis and was 55.6% (15/27) in patients with previous PD-1/L1 treatment. The cORR was 62.2% (28/45) for HER2 IHC2+&FISH+ or IHC3+ patients, 55.6% (5/9) for HER2 IHC2+&FISH unknown patients, and 39.6% (21/53) for HER2 IHC2+&FISH- patients respectively. DCR was 82.2% (95% CI:73.7%, 89.0%). The mPFS was 5.9 (95% CI:4.2, 7.2) months. The mOS was 14.2 (95% CI:9.7, 18.8) months. The median OS follow up time was 19.1 months. Most common treatment-related AEs were hypoaesthesia (50.5%), Leukopenia (49.5%), aspartate aminotransferase increased (43.0%), neutropenia (42.1%), alopecia (40.2%), asthenia (39.3%), alanine aminotransferase increase (35.5%), decreased appetite (31.8%). The grade ≥3 TRAEs (≥5%) only included hypoaesthesia (15.0%), neutropenia (12.1%) and r-GT increased (5.6%). Conclusions: RC48-ADC showed continuously a promising efficacy with a manageable safety profile in HER2-postive mUC patients who had failed at least one line systemic chemotherapy. Clinical trial information: NCT03507166, NCT03809013.
4509 Background: Urothelial carcinoma (UC) is the third largest cancer type with HER2 positive cancer. RC48-ADC is a novel humanized anti-HER2 antibody-drug conjugate (ADC). This study was to evaluate the activity of RC48-ADC in HER2-positive patients with locally advanced or metastatic urothelial carcinoma (mUC). Methods: This study is an open-label, multicenter, single-arm, non-randomized phase II study. Eligibility criteria include: histologically confirmed UC, HER2-positive (IHC 2+ or 3+), ECOG PS 0-1, treated with ≥1 prior systemic treatment. The patients received RC48-ADC treatment alone (2 mg/kg IV infusion, q2w) until disease progression, unacceptable toxicity, withdrawal, or study termination. The primary endpoint was objective response rate (ORR). Progress-free survival (PFS), overall survival (OS), and safety was also assessed. Results: Patient enrollment for this study was completed in November 2018. A total of 43 patients were enrolled, with a median age of 64 years old. At baseline, most patients (37/43) had visceral metastasis. Fourteen (32.6%) patients had received ≥ 2 lines treatment and 8 (18.6%) patients had prior immune checkpoint inhibitor (CPI) therapy in second line treatment. The objective response rate was 60.5% (95% CI: 44.4%, 75.0%) and the DCR was 90.7% (39/43). As of Jan 23, 2019, the median PFS for the overall study population was not yet reached, and the median PFS was 7.8 months (95% CI: 4.9, 10.7) for the 9 patients who started RC48-ADC prior to Jun 30, 2018. The ORR was 70.6% (12/17) in patients with HER2 FISH+ or IHC3+. The ORR was 64.9% (24/37) in patients with visceral metastasis and was 70.0% (14/20) in liver metastasis patients especially. The ORR was 64.3% in patients post to ≥ 2 lines treatment and 75.0% in patients post to immunotherapy. Common treatment-related AEs were leukopenia (51.2%), hypoesthesia (41.9%), alopecia (41.9%), neutropenia (37.2%), fatigue (34.9%), ALT increase (32.6%), and AST increase (32.6%); Most were Grade 1 or 2. Conclusions: RC48-ADC has demonstrated a clinically meaningful ORR of 60.5% in pretreated HER-2 positive mUC patients including those who underwent failure to the immunotherapy. Clinical trial information: NCT03507166.
Renal cell carcinoma is abbreviated as renal carcinoma, and its clinical symptoms are basically hematuria, lumbago, and abdomen bump. As people’s lifestyles change, the incidence of renal carcinoma continues to rise due to factors such as smoking and obesity. At present, surgical treatment is mostly used in clinical practice. Traditional open radical nephrectomy (ORN) is one of the main methods for clinical treatment of renal carcinoma. However, due to its large wound and large amount of intraoperative blood loss, the renal function of patients after surgery is poor, which is not conducive to the postoperative recovery of patients. Retroperitoneal laparoscopic radical nephrectomy (RLRN) has been widely used in the surgical treatment of renal cancer due to its advantages of small wound, less bleeding, and rapid recovery. The purpose of this study was to investigate the efficacy of RLRN in the treatment of renal cancer patients and its effect on renal function and to analyze the related factors affecting postoperative recurrence of patients. We adopt ORN and RLRN, two kinds of treatment, in patients with renal cancer surgery way, contrast analysis of the two groups of operation time, intraoperative blood loss, postoperative intestinal function recovery time, drainage tube indwelling time, length of hospital stay, and other clinical indicators and renal function indexes and use the single factor analysis and multifactor analysis, the relevant factors that affect kidney cancer patients with postoperative recurrence. The results showed that, compared with ORN treatment, RLRN treatment of renal cancer patients has a short operation time, less trauma, quick recovery after surgery, and fewer complications and can effectively alleviate the renal function injury and the body’s inflammatory response, which is worthy of promotion. Postoperative recurrence was related to age, tumor diameter, TNM stage, surgical method, and postoperative immunotherapy.
5005 Background: Both TITAN and ARCHES studies have demonstrated significant clinical benefits of second-generation androgen receptor inhibitors (ARIs) plus ADT versus placebo plus ADT in the treatment of mHSPC. However, first-generation ARIs plus ADT is also widely used in clinic and how superior second-generation ARIs is to first-generation ones remains to be determined. Here, we evaluated the efficacy and safety of SHR3680, a novel oral ARI, versus bicalutamide (Bica) in high-volume mHSPC. Methods: CHART is a randomized, open-label, phase 3 study (NCT03520478). Patients (pts) with mHSPC were randomized 1:1 to ADT plus either SHR3680 (240 mg/d) or Bica (50 mg/d). All pts had high-volume disease adapted from the CHAARTED study. The primary endpoints were radiographic progression-free survival (rPFS) assessed by independent review committee (IRC) and overall survival (OS). As of May 16, 2021, 209 rPFS events per IRC and 153 deaths occurred and a preplanned interim analysis for rPFS was done. Results: 654 pts were randomized to receive SHR3680 (n = 326) or Bica (n = 328). At data cutoff, the median follow-up duration was 22.1 mo in SHR3680 group and 20.4 mo in Bica group. SHR3680 significantly reduced the risk of radiographic progression or death than Bica (HR, 0.44; 95% CI, 0.33-0.58; p < 0.0001; median, not reached vs 25.1 mo). OS data were immature but an improved OS was observed in SHR3680 group compared to Bica group (HR, 0.58; 95% CI, 0.42-0.80; p = 0.0009). All secondary efficacy endpoints favored SHR3680 plus ADT (Table). Frequencies of adverse events of any cause in any grade were similar between groups. Grade ≥3 treatment-related adverse events occurred in 19.2% and 13.9% of pts in SHR3680 and Bica groups, respectively. No seizure occurred in SHR3680 group. Conclusions: SHR3680 plus ADT significantly improved rPFS versus Bica plus ADT in pts with high-volume mHSPC, with a desirable safety profile. New drug application has been submitted to seek approval based on the data presented here. Clinical trial information: NCT03520478. [Table: see text]
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