IMvigor130 clinical trial in patients (pts) with metastatic urothelial carcinoma (mUC): Analysis of upper tract (UT) and lower tract (LT) subgroups.

551 Background: IMvigor130 demonstrated a statistically significant improvement in PFS in pts receiving atezolizumab (atezo; anti–PD-L1) + platinum-based chemotherapy (plt/gemcitabine [gem]; Arm A) vs placebo + plt/gem (Arm C) as first-line treatment for mUC (Grande et al. 2019). Exploratory analyses examined efficacy outcomes in UT and LT mUC subgroups. Methods: Pts with UT and LT mUC from Arm A and Arm C were included. Chemotherapy was gem + investigator choice of plt (cisplatin or carboplatin). Tumors were assessed at baseline and every 9 wk until investigator-assessed PD per RECIST 1.1 or other events. PFS, OS and ORR in UT and LT subgroups are shown. Results: Baseline characteristics were comparable between Arm A and Arm C in the UT and LT subgroups; however, slight imbalances were noted, such as higher PD-L1–positive status (IC2/3) and lower Bajorin risk score in UT Arm A pts. With a median follow-up of 11.8 mo, median PFS was8.2 vs 6.2 mo in Arm A vs Arm C in UT pts (HR, 0.69 [95% CI: 0.51, 0.94]) and 8.1 vs 6.5 mo, respectively, in LT pts (HR, 0.85 [95% CI: 0.70, 1.02]). Interim median OS was 16.9 vs 13.5 mo in Arm A vs Arm C in UT pts (HR, 0.78 [95% CI: 0.54, 1.12]) and 15.8 vs 13.4 mo, respectively, in LT pts (HR, 0.87 [95% CI: 0.70, 1.08]). See table for additional efficacy results. Conclusions: Exploratorysubgroup analyses suggest activity of atezo + plt/gem in both UT and LT mUC, with outcomes in UT pts comparable to those seen in the LT and ITT populations. Clinical trial information: NCT02807636. [Table: see text]

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A phase II study of bevacizumab in combination with irinotecan plus S-1 as first-line treatment in patients with KRAS mutant-type metastatic colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.676 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 676-676

Author(s):

Tetsuya Eto ◽

Toshiki Masuishi ◽

Kohei Suzuki ◽

Isamu Shibata ◽

Yuichi Fukami ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Trial ◽

Primary Tumor ◽

Phase Ii Study ◽

Line Treatment ◽

First Line ◽

Mutant Type ◽

Clinical Trial Information ◽

Line Chemotherapy ◽

First Line Treatment

676 Background: FOLFIRI+bevacizumab (BV) is considered as a first-line treatment in patients (pts) with metastatic colorectal cancer (mCRC). The FIRIS study showed the non-inferiority of irinotecan plus S-1 (IRIS) to FOLFIRI. Therefore, we conducted a phase II study to evaluate the efficacy and safety of BV in combination with IRIS as first-line chemotherapy for KRAS mutant-type (mt) mCRC (clinical trial information: UMIN000004630). Methods: Eligibility criteria included histologically confirmed mCRC, KRAS mt, no previous chemotherapy, ECOG performance status (PS) of 0/1, and adequate organ function. S-1 was administered at 80 mg/m2 on days 1–14 and irinotecan at 100 mg/m2 on days 1 and 15 every 28 days. BV was administered at 5 mg/kg on days 1 and 15 every 28 days. The primary endpoint was response rate (RR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. The sample size was calculated to reject a RR of 25% in favor of a target RR of 50% with a significance level of 0.05 and a statistical power of 80%. Results: Of 26 patients enrolled for the study between December 2010 and September 2015, 23 met the inclusion criteria. The patient characteristics were as follows: median age, 66 (range, 46–77) years; male/female, 15/8; PS 0/1, 9/14; number of metastatic tumors 1/ ≥ 2, 8/15; colon/rectum as the primary tumor site, 13/10; primary tumor +/−, 15/8; and unresectable/recurrent, 15/8. The RR was 60.9% (95% confidence interval (CI): 40.8%–77.8%) with complete response, 0; partial response, 14; stable disease, 8; progressive disease, 0; and not evaluable, 1. With a median follow-up period of 58.1 months, the median PFS and OS were 10.7 (95% CI: 4.7–16.8) and 28.5 (95% CI: 17.6–39.3) months, respectively. The most common grade 3 or 4 adverse events were neutropenia (35%), diarrhea (22%), leukopenia (17%), febrile neutropenia (13%), anemia (13%), and hypoalbuminemia (13%). Conclusions: BV in combination with IRIS as first-line chemotherapy showed promising anti-tumor effects and manageable toxicities for KRAS mt mCRC. Clinical trial information: UMIN000004630.

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Treatment and prognosis of advanced triple-negative breast cancer patients with HER2-low expression: A 15-year retrospective study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e13046 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e13046-e13046

Author(s):

Jiangping Yang ◽

Xi Yan ◽

Jinlan He ◽

Ting Luo ◽

Xiaorong Zhong ◽

...

Keyword(s):

Triple Negative ◽

Early Stage ◽

Treatment Patterns ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Baseline Characteristics ◽

Low Expression ◽

First Line Treatment

e13046 Background: There is some tumor defined HER2 1+ or 2+ by IHC and negative in FISH as HER2 low expression in common triple-negative breast cancer (TNBC). This subset is considered to be a new subtype of HER2-low BC, which might benefit from HER2-targeted antibody drug conjugate (ADC). Therefore, it could preliminarily understand on treatment status and treatment needs of HER2-low BC by analysis of the distribution, treatment patterns and prognosis of HER2-low BC in advanced TNBC. Methods: This was a retrospective study which included HR-negative, HER2 IHC 0/1+/2+ and FISH negative ABC patients (pts) diagnosed from June 2006 to September 2020, with recurrence and de novo metastatic cancer at a single institution in China. The cut-off date of follow-up was 31 December 2020. The baseline characteristics, first- and second-line therapies and the clinical outcomes were reported. Results: In total of 195 pts with complete follow-up data were included into final analysis. HR-negative, HER2 IHC 0 pts (triple negative, TN pts) were 61.5% (n = 120), and HR- negative, HER2 IHC 1 + / 2 + and FISH negative pts (HER2-low pts) were 38.5% (n = 75). The baseline characteristics and treatment patterns of HER2-low pts and TN pts were similar. The median age of pts at diagnosis was 48 years old while 54.4% pts were premenopausal. About 80% pts were recurrence, and 27.6% of them received neoadjuvant chemotherapy. The median disease-free interval (DFI) in early stage was 15.5 months, with 66.0% pts for DFI≥12 months. 56.4% of the pts presented with visceral metastasis. The most common sites of metastasis were lung (35.4%), lymph node (27.7%), soft tissue (24.1%), liver (20.5%), bone (20.5%), and brain (6.2%). The most commonly used regimens for first- and second-line were combination chemotherapy, which were 74.7% and 65.3%, respectively; paclitaxel (55.6%) and platinum (43.8%) were the most commonly used drugs for the first-line treatment. Only 14.4% and 3.6% pts received targeted combination therapy and immunotherapy in advanced setting, respectively. In TN and HER2-low ABC pts, the median PFS of first-line treatment were both 7.2 months, and the median OS was 17.2 months and 17.0 months, respectively. In DFI≥12 months and DFI<12 months subgroup, the median PFS was 8.4 months vs. 4.7 months, with a median OS of 17.8 months vs. 14.4 months, respectively. No significant different was observed between HER2-low pts and TN pts. Conclusions: Based on this observational cohort study, there is no significant difference in the current treatment patterns and prognosis between HER2-low pts and TN pts. However, with the emergence of HER2-targeted ADC therapy, HER2-low ABC pts which were commonly defined as TNBC may benefit from these novel therapies. The recurrence subgroup with DFI≥12 months presented a trend of longer OS, suggesting the therapy mode and response in early stage should be considered in advanced TNBC treatment.

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The randomized phase II study of FOLFOXIRI plus cetuximab versus FOLFOXIRI plus bevacizumab as the first-line treatment in metastatic colorectal cancer with RAS wild-type tumors: The DEEPER trial (JACCRO CC-13).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.3501 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 3501-3501

Author(s):

Akihito Tsuji ◽

Hisatsugu Ohori ◽

Tatsuro Yamaguchi ◽

Masato Matsuura ◽

Atsujiro Nishioka ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Trial ◽

Primary Endpoint ◽

Line Treatment ◽

Wild Type ◽

First Line ◽

Randomized Phase Ii ◽

Secondary Endpoints ◽

Clinical Trial Information ◽

First Line Treatment

3501 Background: Triplet regimens, FOLFOXIRI, combined with bevacizumab (bev) or panitumumab have been shown to be superior in terms of early tumor shrinkage (ETS) and depth of response (DpR) compared to doublet combinations in patients with RAS wild-type metastatic colorectal cancer (mCRC), in the TRIBE trial ( N Engl J Med 2014) or the VOLFI trial ( J Clin Oncol 2019), respectively. There have been few studies which directly compared cetuximab (cet) with bev when combined with triplet regimen. Therefore, we investigated the efficacy and safety of bev vs. cet in combination with FOLFOXIRI in previously untreated mCRC patients with RAS wild-type tumors. Methods: This trial was a randomized phase II trial to evaluate modified (m)-FOLFOXIRI (irinotecan 150mg/m2, oxaliplatin 85mg/m2, 5-FU 2400mg/m2) plus cet vs. bev as first-line treatment in terms of DpR during the entire course as the primary endpoint in 360 patients with RAS wild-type mCRC. The aim of the trial was to show that median DpR of cet arm was more than 12.5% higher than bev arm, with a power of 85% at a significance level of 0.05. Secondary endpoints included ETS rate at week 8, overall response rate (ORR), progression-free survival (PFS), overall survival (OS), secondary resection rate, and toxicity. Results: A total of 359 patients were enrolled between July 2015 and June 2019. For the full analysis set (median age 65y, 64% male, PS0/1: 91%/9%, left/right primary: 83%/17%), 173 and 175 patients were randomly assigned to the cet and bev arms, respectively. On the cutoff date of September 2020, the median number of cycles administered was 10 (range, 1-51) for the cet arm and 12 (range, 1-51) for the bev arm. Safety data was already reported at the ASCO GI symposium 2021 (J Clin Oncol 39, 2021 suppl 3; abstr 86). The primary endpoint was met (p =.001); 57.4%（-15.0̃100）for the cet arm versus 46.0% （-0.6̃100）for the bev arm. As for primary tumor sidedness, median DpR were 60.3% versus 46.1% (p =.0007) in the left-side and 50.0% versus 41.2% (p =.46) in the right-side. The ETS rate and ORR as the secondary endpoints were 77.8% and 69.1% in the cet arm versus 74.6% and 71.7% in the bev arm, respectively, with no statistical significance. Although the survival data were immature, PFS and OS of both arms were 12.7 months (95%CI 11.5-14.0) and 37.6 months (95%CI 30.8 to 43.0), respectively. Conclusion: The mFOLFOXIRI plus cet has been shown to be significantly superior to the mFOLFOXIRI plus bev in terms of DpR as the primary endpoint in first-line treatment for RAS wild-type mCRC. Clinical trial information: NCT02515734. Clinical trial information: UMIN000018217.

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Efficacy and safety of KN046 plus paclitaxel/cisplatin as first-line treatment for unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.4062 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 4062-4062

Author(s):

Jianming Xu ◽

Rongrui Liu ◽

Yanqiao Zhang ◽

Nong Xu ◽

Qingxia Fan ◽

...

Keyword(s):

Clinical Trial ◽

Squamous Cell Carcinoma ◽

Adverse Events ◽

Esophageal Squamous Cell Carcinoma ◽

Locally Advanced ◽

Line Treatment ◽

Efficacy And Safety ◽

First Line ◽

Clinical Trial Information ◽

First Line Treatment

4062 Background: The prognosis of pts with advanced esophageal squamous cell carcinoma (ESCC) remains dismal clinically. Paclitaxel and cisplatin were used as the standard first-line regimen in ESCC for almost two decades. Recently, the combination of PD-1/PD-L1 pathway blockades with chemotherapy has shown synergistic efficacy in a few clinical trials. KN046 is the world's first dual immune checkpoint inhibitor, which can block PD-1/PD-L1 and CTLA-4 pathways at the same time. The purpose of this ongoing phase II trial (NCT03925870) in China was to evaluate the efficacy and safety of KN046 monotherapy or combined with chemotherapy for unresectable locally advanced, recurrent or metastatic ESCC. Methods: This trial included 3 cohorts, one of which enrolled systemic treatment naïve pts with histologically or cytologically confirmed unresectable locally advanced, recurrent or metastatic ESCC who have ECOG PS of 0-1. Eligible subjects were given paclitaxel (135-175mg/m2, iv, d1, q3w) and cisplatin (75mg/m2, iv, d2-4, q3w) plus KN046 (5mpk, iv, d1, q3w) for 4̃6 cycles during initial therapy. For those without progressive disease, maintenance treatment was administrated with KN046 monotherapy (5mpk, iv, q2w) until progression or unacceptable toxicity. Tumour response was assessed according to RECIST 1.1 every 6 weeks. The primary endpoint was investigator-assessed ORR. Secondary endpoints included DCR, safety, PK profile, and immunogenicity. Results: As of December 14, 2020, 15 pts were enrolled, all of them were male, 52.3% ≥60 years, 64% ECOG 1, 80% with distant metastasis. Median exposure time to KN046 was 11.4 wks and average KN046 treatment was 2.4 cycles. 12 pts were included in the efficacy analysis and 15 pts in the safety analysis. The overall response rate (ORR) and disease control rate (DCR) were 58.3% and 91.6%, respectively. 7 pts (58.3%) had partial response (PR) including one complete response of target lesion. 4 pts (33.3%) had stable disease (SD) with 3 pts showing more than 20% of tumor burden reduction. The overall incidence of KN046 related adverse events was 80.0%, with 13.3% Gr 3 or above TRAE. Infusion-related adverse events occurred during 7.8% and most were mild. Immune related adverse events（irAE）were seen in 53.3% and the most common Gr 3 irAE were nausea (n＝1, 6.7%) and rash (n＝1, 6.7%). Conclusions: KN046 plus paclitaxel/cisplatin demonstrated clinical efficacy and acceptable safety as first-line treatment, and might be a favorable option for pts with advanced ESCC. Clinical trial information: NCT03925870. Research Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd. Clinical trial information: NCT03925870.

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