Efficacy and safety of immune checkpoint inhibitors and cytokine therapy in autoimmune diseases

TPS178 Background: Immune checkpoint inhibitors are drugs that block specific proteins produced by the immune system cells, such as T-cells; these proteins prevent T-cells from killing cancer cells. NIV is a standard care for pretreated mGC patients (pts), with increasing clinical use in Japan. Data from retrospective studies on various tumors have shown that after exposure to immune checkpoint inhibitors, the objective response rate to CTx potentially improves; however, enough data have not been accumulated. Although there are no recommended CTx regimen following NIV therapy, in a clinical setting, an irinotecan or oxaliplatin combination regimen (limited to cisplatin-refractory or cisplatin-intolerant pts) is frequently used as post-NIV CTx. This multicenter observational study aims to evaluate the efficacy and safety of CTx in NIV-refractory or NIV-intolerant mGC pts. Methods: We prospectively collect clinical and imaging data from NIV-pretreated mGC pts; these pts will be treated with cytotoxic agents. Pts who meet inclusion criteria A (histologically proven mGC pretreated with NIV, prior administration of a combination therapy of fluoropyrimidine plus platinum and taxanes, and written informed consent) at primary registration are registered. After primary registration, pts who meet inclusion criteria B [Eastern Cooperative Oncology Group Performance Status (ECOG PS 0-2), refractory or intolerant to NIV; prior administration of irinotecan monotherapy or oxaliplatin combination regimens and prior use of cisplatin; evaluable lesions according to RECIST ver. 1.1] at formal registration are registered. The primary endpoint is overall survival of NIV-pretreated mGC pts after CTx. For this study, we require 146 pts, with bilateral alpha = 0.05 and beta = 0.10, with a median threshold survival of 4.0 months and an expected median survival of 6.0 months. Therefore, we plan to enroll 200 pts, considering exclusions from the analysis; since May 2018, we have enrolled 27 pts. Clinical trial information: UMIN000032182.

Download Full-text

Immune checkpoint inhibitors plus neoadjuvant chemotherapy in early triple-negative breast cancer: a systematic review and meta-analysis

BMC Cancer ◽

10.1186/s12885-021-08997-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yuanfang Xin ◽

Guoshuang Shen ◽

Yonghui Zheng ◽

Yumei Guan ◽

Xingfa Huo ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Triple Negative ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Efficacy And Safety ◽

Intention To Treat

Abstract Purpose Some studies have shown that Immune checkpoint inhibitors (ICIs) have a favorable efficacy in advanced triple negative breast cancer (TNBC) patients, but the results are controversial in neoadjuvant chemotherapy (NACT) stage. The purpose of this study is to evaluate the efficacy and safety after NACT plus ICIs in early TNBC patients. Methods After searching PubMed, EMBASE, the Cochrane library and several mainly oncology conferences up to 30 January 2021 systematically, and define randomized controlled trials (RCTs) exploring the efficacy and safety of programmed death protein-1/programmed cell death-Ligand 1(PD-1/PD-L1) inhibitors plus neoadjuvant chemotherapy in TNBC patients. The primary endpoint was the pathological complete response (pCR) in intention-to-treat populations (ITT), and the secondary endpoints were event-free survival (EFS) and safety analysis in the ITT populations. Results Six RCTs (N = 2142) were included in our meta-analysis; NACT plus ICIs increased pCR rates compared with NACT in intention-to-treat (ITT) populations (OR: 1.91; 95% CI: 1.32–2.78, P < 0.001). The pCR rate also increased in both PD-L1 positive (OR: 1.65; 95% CI: 1.26–2.16, P < 0.001) and PD-L1 negative patients (OR: 1.56; 95% CI: 1.04–2.33, P = 0.03), especially in PD-L1 positive patients. The benefit was also observed in nodal-positive populations (OR: 2.52; 95% CI: 1.69–3.77, P < 0.001) and Eastern Cooperative Oncology Group performance-status score (ECOG PS) 0 subgroup (OR: 1.90; 95% CI: 1.42–2.53, P < 0.001). Three RCTs (N = 1615) reported EFS and the results showed that adding PD-1/PD-L1 inhibitors increased EFS (HR 0.65, 95% CI 0.50–0.83, P = 0.0007) in ITT populations with a short follow-up time. In the safety analysis of 2205 patients with early TNBC from five eligible studies, NACT plus ICIs had a higher risk of grade 3–4 diarrhea (OR: 2.54; 95% CI: 1.21–5.32; P = 0.01), any grade of adverse effects(AEs)including vomiting (OR: 1.37; 95% CI: 1.00–1.86; P = 0.05), hyperthyroidism (OR: 6.04; 95% CI: 2.39–15.29; P < 0.001), and hypothyroidism (OR: 5.04; 95% CI: 3.02–8.39; P < 0.001). Conclusions PD-1/PD-L1 inhibitors combined with chemotherapy can improve pCR rates and EFS, and with an increased incidence of some immune-related AEs compared with chemotherapy alone. NACT plus ICIs might be an option in patients with in PD-L1 positive and high-risk populations with positive nodal disease early TNBC.

Download Full-text

Immune Checkpoint Inhibitors Plus Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis.

10.21203/rs.3.rs-671558/v1 ◽

2021 ◽

Author(s):

Yuanfang Xin ◽

Guoshuang Shen ◽

Yonghui Zheng ◽

Yumei Guan ◽

Xingfa Huo ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Triple Negative ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Efficacy And Safety ◽

Intention To Treat

Abstract Purpose: Some studies have shown that Immune checkpoint inhibitors (ICIs) have a favorable efficacy in advanced triple negative breast cancer (TNBC) patients, but the results are controversial in neoadjuvant chemotherapy (NACT) stage. The purpose of this study is to evaluate the efficacy and safety after NACT plus ICIs in early TNBC patients.Methods: After searching PubMed, EMBASE, the Cochrane library and several mainly oncology conferences up to 30 January 2021 systematically, and define randomized controlled trials (RCTs) exploring the efficacy and safety of PD-1/PD-L1 inhibitors plus neoadjuvant chemotherapy in TNBC patients. The primary endpoint was the pathological complete response (pCR) in intention-to-treat populations (ITT), and the secondary endpoints were event-free survival (EFS) and safety analysis in the ITT populations.Results: Six RCTs (N = 2142) were included in our meta-analysis; NACT plus ICIs increased pCR rates compared with NACT in intention-to-treat (ITT) populations (OR: 1.91; 95% CI: 1.32–2.78, P < 0.001). The pCR rate also increased both in PD-L1 positive (OR: 1.65; 95% CI: 1.26–2.16, P < 0.001) and negative patients (OR: 1.56; 95% CI: 1.04–2.33, P = 0.03), especially in PD-L1 positive patients. The benefit was also observed in nodal-positive populations (OR: 2.52; 95% CI: 1.69–3.77, P < 0.001) and Eastern Cooperative Oncology Group performance-status score (ECOG PS) 0 subgroup (OR: 1.90; 95% CI: 1.42–2.53, P < 0.001). Three RCTs (N = 1615) reported that EFS and the addition of PD-1/PD-L1 inhibitors increased EFS (HR 0.66, 95% CI 0.48–0.92, P = 0.01) in ITT populations with a short follow-up time. In the safety analysis of 2205 patients with early TNBC from five eligible studies, NACT plus ICIs had a higher risk of grade 3-4 diarrhea (OR: 2.54; 95% CI: 1.21–5.32; P = 0.01), any grade of AEs including vomiting (OR: 1.37; 95% CI: 1.00–1.86; P = 0.05), hyperthyroidism (OR: 6.04; 95% CI: 2.39–15.29; P < 0.001), and hypothyroidism (OR: 5.04; 95% CI: 3.02–8.39; P < 0.001).Conclusions: NACT plus ICIs might be an option in patients with early TNBC.

Download Full-text