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1.
Multicenter phase II study of nivolumab in Japanese patients with relapsed or refractory classical Hodgkin lymphoma 下载免费PDF全文
Dai Maruyama Kiyohiko Hatake Tomohiro Kinoshita Noriko Fukuhara Ilseung Choi Masafumi Taniwaki Kiyoshi Ando Yasuhito Terui Yusuke Higuchi Yasushi Onishi Yasunobu Abe Tsutomu Kobayashi Yukari Shirasugi Kensei Tobinai 《Cancer science》2017,108(5):1007-1012
Overexpression of programmed death‐1 (PD‐1) ligands contributes to an immunosuppressive microenvironment. Nivolumab is a PD‐1‐blocking antibody that inhibits the PD‐1 pathway and showed good efficacy in several types of malignancy. This phase II study examined the efficacy and safety of nivolumab in 17 Japanese patients with refractory/relapsed classical Hodgkin lymphoma previously treated with brentuximab vedotin. Sixteen patients were included in efficacy analyses and 17 in safety analyses. The primary endpoint was the centrally assessed objective response rate (ORR). The study was commenced in March 2015. We report data obtained at a cutoff of 16 March 2016, at which time 11 patients were still receiving nivolumab. The median (range) duration of treatment and follow‐up were 7.0 (1.4–10.6) months and 9.8 (6.0–11.1) months, respectively. All 17 patients had previously received brentuximab vedotin. The ORR was 81.3% (95% confidence interval [CI]: 54.4–96.0%; 13/16 patients), with complete remission and partial remission in 4 and 9 patients, respectively. The overall survival (OS) and progression‐free survival (PFS) rates at 6 months were 100 and 60.0% (95% CI: 31.8–79.7%), respectively; the median OS and PFS were not reached. The most common adverse events (AE) were pyrexia (41.2%), pruritus (35.3%), rash (35.3%) and hypothyroidism (29.4%). Four patients (23.5%) experienced grade 3 or 4 AE, but most AE were of grade 1 or 2. In conclusion, nivolumab is a potentially effective and tolerable treatment option for Japanese patients with relapsed/refractory classical Hodgkin lymphoma previously treated with brentuximab vedotin. 相似文献
2.
Naoya Yamazaki Yoshio Kiyohara Hisashi Uhara Jiro Uehara Yasuhiro Fujisawa Tatsuya Takenouchi Masaki Otsuka Hiroshi Uchi Hironobu Ihn Masahiro Hatsumichi Hironobu Minami 《Cancer science》2019,110(6):1995-2003
The immune checkpoint inhibitor nivolumab inhibits the programmed death 1 receptor and suppresses the immune resistance of cancer cells. This is a long‐term follow up of a single‐arm, open‐label, multicenter, phase II study of nivolumab in untreated Japanese patients with stage III/IV or recurrent melanoma. In addition, a post–hoc subgroup analysis stratified by melanoma types was performed. Nivolumab was administered intravenously at a dose of 3 mg/kg every 2 weeks. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression‐free survival (PFS), best overall response, the disease control rate and change in tumor diameter. Safety was assessed by recording treatment‐related adverse events (TRAE), including select immune‐related adverse events. Of the 24 patients initially included in the primary phase II study, 10 survived for over 3 years (41.7%). The ORR was 34.8% (90% confidence interval [CI]: 20.8, 51.9) for all patients. When analyzing by melanoma type, the ORR was 66.7% (90% CI: 34.7, 88.3) for superficial spreading, 33.3% (90% CI: 11.7, 65.3) for mucosal, and 28.6% (90% CI: 10.0, 59.1) for acral lentiginous tumors. The median OS was 32.9 months, the 3‐year OS rate was 43.5%, and the 3‐year PFS rate was 17.2%. A long‐term response was observed in all the tumor types. The most common TRAE included skin toxicity (45.8%) and endocrine disorders (29.2%). This study demonstrated the long‐term efficacy and tolerability of nivolumab in patients with advanced or recurrent melanoma, irrespective of melanoma type. 相似文献
3.
Efficacy and safety of nivolumab in Japanese patients with advanced or recurrent squamous non‐small cell lung cancer 下载免费PDF全文
Toyoaki Hida Makoto Nishio Naoyuki Nogami Yuichiro Ohe Hiroshi Nokihara Hiroshi Sakai Miyako Satouchi Kazuhiko Nakagawa Mitsuhiro Takenoyama Hiroshi Isobe Shiro Fujita Hiroshi Tanaka Koichi Minato Toshiaki Takahashi Makoto Maemondo Koji Takeda Hideo Saka Koichi Goto Shinji Atagi Tomonori Hirashima Naoki Sumiyoshi Tomohide Tamura 《Cancer science》2017,108(5):1000-1006
Limited treatment options are available for stage IIIB/IV non‐small cell lung cancer (NSCLC). Nivolumab, a programmed cell death‐1 immune checkpoint inhibitor antibody, has been shown to be effective for the treatment of NSCLC. The present study investigated the effectiveness and safety of nivolumab in Japanese patients with advanced or recurrent squamous NSCLC that progressed after platinum‐containing chemotherapy. In this multicenter phase II study, patients were treated with nivolumab (3 mg/kg, i.v.) every 2 weeks until progressive disease or unacceptable toxicity was seen. Primary endpoint was overall response rate (ORR) assessed by independent radiology review committee (IRC) and secondary endpoints included a study site‐assessed ORR, overall survival (OS), progression‐free survival (PFS), duration of response, time to response, best overall response (BOR), and safety. The study included 35 patients from 17 sites in Japan. Patients had IRC‐assessed ORR of 25.7% (95% CI 14.2, 42.1) and the study site‐assessed ORR was 20.0% (95% CI 10.0, 35.9). Median OS, median time to response and median PFS were 16.3 (95% CI 12.4–25.4), 2.7 (range 1.2–5.5) and 4.2 (95% CI 1.4–7.1) months, respectively. The IRC‐assessed BOR was partial response, stable disease, and progressive disease for 25.7%, 28.6%, and 45.7% of patients, respectively. Treatment‐related adverse events were reported in 24 patients (68.6%), most of which resolved with appropriate treatment including steroid therapy or ?discontinuation of nivolumab. Nivolumab was effective and well tolerated in Japanese patients with advanced or recurrent squamous NSCLC that progressed after platinum‐containing chemotherapy. Clinical trial registration number: JapicCTI‐132072 相似文献
4.
Kenji Tamura Kosei Hasegawa Noriyuki Katsumata Koji Matsumoto Hirofumi Mukai Shunji Takahashi Hiroyuki Nomura Hironobu Minami 《Cancer science》2019,110(9):2894-2904
Nivolumab is a human monoclonal antibody against the immune checkpoint receptor programmed death‐1, inhibiting binding to programmed death‐ligand 1 or 2 (PD‐L1 or PD‐L2). This phase 2 study evaluated the efficacy and safety of nivolumab in patients with advanced/recurrent uterine cervical cancer, uterine corpus cancer, or soft tissue sarcoma (STS). Patients received nivolumab 240 mg at 2‐week intervals. Primary endpoint was objective response rate; secondary endpoints included overall survival, progression‐free survival, and safety. PD‐L1 expression and microsatellite‐instability (MSI) status were analyzed as potential efficacy biomarkers. Objective response rate was 25%, 23%, and 0% in patients with cervical cancer (n = 20), corpus cancer (n = 22), and STS (n = 21), respectively. The lower 80% confidence intervals of objective response rates in patients with cervical or corpus cancer exceeded the threshold rate (5%); the primary endpoint was met in cervical and corpus cancer, but not in STS. Median progression‐free survival was 5.6, 3.4, and 1.4 months, and 6‐month overall survival was 84%, 73%, and 86% in cervical cancer, corpus cancer, and STS, respectively. The objective response rate was higher in patients with cervical cancer with PD‐L1‐positive (n = 5/15; 33%) versus PD‐L1‐negative (n = 0/5; 0%) tumors. The two patients with corpus cancer classified as MSI‐high responded; the six patients classified as microsatellite stable did not respond. Overall, nivolumab showed acceptable toxicity in all cohorts, with evidence of clinical activity in uterine cervical or corpus cancer, but not in STS. PD‐L1 expression in cervical cancer and MSI‐high in corpus cancer may predict clinical activity of nivolumab in these cancers. 相似文献
5.
Cytokine biomarkers to predict antitumor responses to nivolumab suggested in a phase 2 study for advanced melanoma 下载免费PDF全文
Hisashi Uhara Hajime Iizuka Jiro Uehara Fujio Otsuka Yasuhiro Fujisawa Tatsuya Takenouchi Taiki Isei Keiji Iwatsuki Hiroshi Uchi Hironobu Ihn Hironobu Minami Hideaki Tahara 《Cancer science》2017,108(5):1022-1031
Promising antitumor activities of nivolumab, a fully humanized IgG4 inhibitor antibody against the programmed death‐1 protein, were suggested in previous phase 1 studies. The present phase 2, single‐arm study (JAPIC‐CTI #111681) evaluated the antitumor activities of nivolumab and explored its predictive correlates in advanced melanoma patients at 11 sites in Japan. Intravenous nivolumab 2 mg/kg was given repeatedly at 3‐week intervals to 35 of 37 patients enrolled from December 2011 to May 2012 until they experienced unacceptable toxicity, disease progression, or complete response. Primary endpoint was objective response rate. Serum levels of immune modulators were assessed at multiple time points. As of 21 October 2014, median response duration, median progression‐free survival, and median overall survival were 463 days, 169 days, and 18.0 months, respectively. The overall response rate and 1‐ and 2‐year survival rates were 28.6%, 54.3%, and 42.9%, respectively. Thirteen patients remained alive at the end of the observation period and no deaths were drug related. Grade 3–4 drug‐related adverse events were observed in 31.4% of patients. Pretreatment serum interferon‐γ, and interleukin‐6 and ‐10 levels were significantly higher in the patients with objective tumor responses than in those with tumor progression. In conclusion, giving repeated i.v. nivolumab had potent and durable antitumor effects and a manageable safety profile in advanced melanoma patients, strongly suggesting the usefulness of nivolumab for advanced melanoma and the usefulness of pretreatment serum cytokine profiles as correlates for predicting treatment efficacy. 相似文献
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Naoya Yamazaki Taiki Isei Yoshio Kiyohara Hiroshi Koga Takashi Kojima Tatsuya Takenouchi Kenji Yokota Kenjiro Namikawa Min Yi Alissa Keegan Satoshi Fukushima 《Cancer science》2022,113(8):2798
Talimogene laherparepvec (T‐VEC) is approved for the treatment of unresectable melanoma in the USA, Europe, and Australia. This phase I, multicenter, open‐label, dose de‐escalation study evaluated the safety and efficacy of T‐VEC in Japanese patients with unresectable stage IIIB–IV melanoma. Eligible adult patients had histologically confirmed stage IIIB–IVM1c cutaneous melanoma, may have received prior systemic anticancer therapy, must have had ≥1 injectable lesion, serum lactate dehydrogenase ≤1.5x upper limit of normal, ECOG performance status of 0 or 1, and adequate hematologic, hepatic, and renal function. T‐VEC was injected intralesionally (first dose, ≤4.0 ml of 106 PFU/ml; after 3 weeks and then every 2 weeks thereafter, ≤4.0 ml of 108 PFU/ml). Primary endpoints were dose‐limiting toxicities (DLTs) and durable response rate (DRR). Of 18 enrolled patients (72.2% female), 16 had received ≥1 prior line of therapy. Ten patients discontinued T‐VEC due to disease progression. Median (range) follow‐up was 20.0 (4–37) months. No DLTs were observed; 17 (94.4%) patients had treatment‐emergent adverse events (AEs). Fourteen (77.8%) patients had treatment‐related AEs; the most frequent were pyrexia (44.4%), malaise (16.7%), chills, decreased appetite, pruritus, and skin ulcer (11.1% each). The primary efficacy endpoint was met: 2 (11.1%) patients had a durable partial response ≥6 months. The DRR was consistent with that observed in a phase III trial of T‐VEC in non‐Asian patients. The safety profile was consistent with the patients'' underlying disease and the known safety profile of T‐VEC. 相似文献
7.
Do-Youn Oh MD PhD Alain Algazi MD Jaume Capdevila MD PhD Federico Longo MD Wilson Miller Jr. MD PhD Jerry Tan Chun Bing MD Carlos Eduardo Bonilla MD Hyun Cheol Chung MD Tormod K. Guren MD PhD Chia-Chi Lin MD PhD Daniel Motola-Kuba MD Manisha Shah MD Julien Hadoux MD PhD Lili Yao PhD Fan Jin MD Kevin Norwood MD Loïc Lebellec MD 《Cancer》2023,129(8):1195-1204
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Hussein A Tawbi Peter A Forsyth F Stephen Hodi Christopher D Lao Stergios J Moschos Omid Hamid Michael B Atkins Karl Lewis Reena P Thomas John A Glaspy Sekwon Jang Alain P Algazi Nikhil I Khushalani Michael A Postow Anna C Pavlick Marc S Ernstoff David A Reardon Igor Puzanov Ragini R Kudchadkar Ahmad A Tarhini Anne Sumbul Jasmine I Rizzo Kim A Margolin 《Neuro-oncology》2021,23(11):1961
BackgroundIn patients with melanoma and asymptomatic brain metastases (MBM), nivolumab plus ipilimumab provided an intracranial response rate of 55%. Here, we present the first report for patients who were symptomatic and/or required corticosteroids and updated data for asymptomatic patients.MethodsPatients with measurable MBM, 0.5-3.0 cm, were enrolled into Cohort A (asymptomatic) or Cohort B (stable neurologic symptoms and/or receiving corticosteroids). Nivolumab, 1 mg/kg, and ipilimumab, 3 mg/kg, were given intravenously every 3 weeks ×4, followed by nivolumab, 3 mg/kg, every 2 weeks until progression, unacceptable toxicity, or 24 months. The primary endpoint was intracranial clinical benefit rate (CBR; complete response [CR], partial response [PR], or stable disease ≥6 months).ResultsSymptomatic patients (N = 18) received a median of one nivolumab and ipilimumab combination dose and had an intracranial CBR of 22.2%. Two of 12 patients on corticosteroids had CR; 2 responded among the 6 not on corticosteroids. Median intracranial progression-free survival (PFS) and overall survival (OS) were 1.2 and 8.7 months, respectively. In contrast, with 20.6 months of follow-up, we confirmed an intracranial CBR of 58.4% in asymptomatic patients (N = 101); median duration of response, PFS, and OS were not reached. No new safety signals were observed.ConclusionsNivolumab plus ipilimumab provides durable clinical benefit for asymptomatic patients with MBM and should be considered for first-line therapy. This regimen has limited activity in MBM patients with neurologic symptoms and/or requiring corticosteroids, supporting the need for alternative approaches and methods to reduce the dependency on corticosteroids. Clinical trial registration. ClinicalTrials.gov, . NCT02320058相似文献
9.
Alexander N. Shoushtari MD Deborah Kuk MS Patrick A. Ott MD PhD Douglas B. Johnson MD Katy K. Tsai MD Suthee Rapisuwon MD Zeynep Eroglu MD Ryan J. Sullivan MD Jason J. Luke MD Tara C. Gangadhar MD April K. S. Salama MD Varina Clark BA Clare Burias BA Igor Puzanov MD Michael B. Atkins MD Alain P. Algazi MD Antoni Ribas MD PhD Jedd D. Wolchok MD PhD Michael A. Postow MD 《Cancer》2016,122(21):3354-3362
10.
Shintaro Kanda Yuichiro Ohe Yasushi Goto Hidehito Horinouchi Yutaka Fujiwara Hiroshi Nokihara Noboru Yamamoto Takanori Yamamoto Tomohide Tamura 《Cancer science》2020,111(6):1933-1942
Combination antiprogrammed death 1/programmed death‐ligand 1 Ab and platinum‐based chemotherapy is standard first‐line treatment for advanced non‐small‐cell lung cancer without targetable oncogene alterations. We describe the long‐term safety and efficacy data from a previously reported phase Ib study of nivolumab and chemotherapy. Japanese patients with non‐small‐cell lung cancer were assigned to a treatment arm based on histology and treatment history. Nivolumab (10 mg/kg, i.v.) and chemotherapy (4 arms) were given every 3 weeks: arm A, 4 cycles of cisplatin and gemcitabine (first‐line); arm B, 4 cycles of cisplatin and pemetrexed followed by pemetrexed maintenance therapy (first‐line); arm C, 4‐6 cycles of carboplatin, paclitaxel, and bevacizumab followed by bevacizumab (first‐line); and arm D, docetaxel (second‐ or third‐line). Study treatments were continued every 3 weeks as maintenance therapy until disease progression. Minimum follow‐up period was 57.9 months. Median progression‐free survival (median [range, plus sign indicates censored data]) was 6.3 (0.7+‐47.8), 11.8 (1.4‐65.1+), 40.7 (5.3‐60.8+), and 3.2 (1.9‐10.9) months, and 5‐year progression‐free survival was observed in 0/6, 1/6, 1/6, and 0/6 patients in arms A, B, C, and D, respectively. Median overall survival was 13.2 (11.0‐55.4), 28.5 (14.6‐66.2+), not reached (24.2‐67.4+), and 12.5 (9.8‐16.9) months; the number of patients surviving 5 years were 0/6, 1/6, 4/6, and 0/6 in arms A, B, C, and D, respectively. No unexpected severe adverse events or treatment‐related deaths occurred. Nivolumab and platinum‐based chemotherapy combinations showed long‐term tolerability. A moderate proportion of patients in arm C showed 5‐year progression‐free and overall survival. 相似文献
11.
Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials 下载免费PDF全文
Karen Kelly MD Jeffrey R. Infante MD Matthew H. Taylor MD Manish R. Patel MD Deborah J. Wong MD PhD Nicholas Iannotti MD Janice M. Mehnert MD Anja H. Loos PhD Helga Koch PhD Isabell Speit MD James L. Gulley MD PhD 《Cancer》2018,124(9):2010-2017
12.
Ken Kato Yuichiro Doki Takashi Ura Yasuo Hamamoto Takashi Kojima Takahiro Tsushima Shuichi Hironaka Hiroki Hara Toshihiro Kudo Satoru Iwasa Kei Muro Hirofumi Yasui Keiko Minashi Kensei Yamaguchi Atsushi Ohtsu Yuko Kitagawa 《Cancer science》2020,111(5):1676-1684
The long‐term efficacy of nivolumab in esophageal squamous cell carcinoma and its association with disease biomarkers are currently not well known. Therefore, we investigated the association in Japanese patients with treatment‐refractory advanced esophageal cancer who participated in an open‐label, single‐arm, multicenter phase II study. Patients received nivolumab 3 mg/kg i.v. every 2 weeks until disease progression or unacceptable toxicity, and were followed up for 2 years after the initial dosing of the last patient. Archival tissue samples were collected before treatment and analyzed for programmed death ligand‐1 (PD‐L1) and CD8+ status of tumors and tumor‐infiltrating lymphocytes (TILs) and human leukocyte antigen class 1. Efficacy end‐points included objective response rate (ORR), overall survival (OS), progression‐free survival (PFS), time to response, and duration of response. Of 65 enrolled patients (83% male), 64 were evaluable for efficacy and 41 (63%) for biomarkers. The ORR, median OS, and survival rate were 17.2%, 10.78 months, and 17.2%, respectively. Time to response was 1.45 months and duration of response was 11.17 months. The PD‐L1 positivity of tumor cells was possibly associated with better PFS (2.04 vs 1.41 months, cut‐off 1%) and OS (11.33 vs 6.24 months, cut‐off 1%). Median OS was prolonged in patients with a median number of TILs greater than 63.75% vs 63.75% or less (11.33 vs 7.85 months). Nivolumab showed continued long‐term efficacy, as seen by the stability of PFS and OS, in Japanese patients with esophageal squamous cell carcinoma. Further investigation of PD‐L1 tumor expression and TILs as potential biomarkers for predicting patients likely to benefit from nivolumab therapy is warranted. 相似文献
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Di Bei Mayu Osawa Shinji Uemura Tomoya Ohno Jogarao Gobburu Amit Roy Mayumi Hasegawa 《Cancer science》2020,111(2):528-535
Nivolumab 3 mg/kg every 2 weeks (Q2W) has been approved in Japan for various cancers; however, use of a flat dose is expected to simplify dosing and administration. A quantitative clinical pharmacology approach was used to assess the benefit‐risk profile of nivolumab 240 mg Q2W relative to the approved dose of nivolumab 3 mg/kg Q2W in Japanese patients. Three exposure‐response safety analyses were performed for adverse events that led to discontinuation/death, were grade 3 or higher, and were immune‐mediated and grade 2 or higher for Japanese patients diagnosed with one of multiple tumor types. Exposure‐response analyses of efficacy were evaluated for overall survival and objective response rate. Exposures of nivolumab 240 mg Q2W were 37% higher than those of nivolumab 3 mg/kg Q2W in Japanese patients across the tumor types analyzed. Predicted safety profiles at the two doses differed by less than 2% across tumor types for adverse events leading to discontinuation/death, adverse events of grade 3 or higher, or immune‐mediated adverse events of grade 2 or higher. In addition, the predicted 1‐year and 2‐year overall survival rates, the mean overall survival and the objective response rates were comparable between the doses regardless of the tumor type analyzed. Overall, these results demonstrated that the benefit‐risk of nivolumab 240 mg Q2W was comparable to that of the previously approved 3 mg/kg Q2W dosing regimen, and was the basis for the approval of the 240 mg Q2W as an alternative dosing regimen for treatment in Japanese patients across multiple tumor types. 相似文献
15.
Looking for the best immune‐checkpoint inhibitor in pre‐treated NSCLC patients: An indirect comparison between nivolumab,pembrolizumab and atezolizumab 下载免费PDF全文
Lorena Incorvaia Angela Listì Viviana Bazan Antonio Russo 《International journal of cancer. Journal international du cancer》2018,142(6):1277-1284
Immune‐checkpoint inhibitors represent the new standard of care in patients with advanced NSCLC who progressed after first‐line treatment. This work aim to assess any difference in both efficacy and safety profiles among Nivolumab, Pembrolizumab and Atezolizumab in pre‐treated NSCLC patients. Randomized clinical trials comparing immune‐checkpoint inhibitor versus docetaxel in pre‐treated patients with advanced NSCLC were included and direct comparison meta‐analysis of selected trials have been performed. Subsequently the summary estimates of Nivolumab, Pembrolizumab and Atezolizumab emerging from the direct meta‐analysis were selected to provide the pooled estimates of hazard ratio (HR) and relative risk (RR) for the indirect comparisons among these agents. A total of 5 studies met the selection criteria and were included in the meta‐analysis. Indirect comparisons for efficacy outcomes showed the RR for ORR nivolumab versus atezolizumab 1.66 (95% CI 1.07?2.58), pembrolizumab versus atezolizumab 1.94 (95% CI 1.30?2.90). No significant differences in both PFS and OS have been observed. Indirect comparisons for safety showed the RR for G3‐5 AEs nivolumab versus pembrolizumab 0.41 (95% CI 0.29?0.60), nivolumab versus atezolizumab 0.50 (95% CI 0.35?0.72). No significant differences in both pneumonitis and discontinuation rate have been observed. The results of this work revealed that nivolumab and pembrolizumab are associated with a significant increase of ORR as compared to atezolizumab and nivolumab is associated with a significant lower incidence of G3‐5 AEs as compared to the other drugs. These evidences could support the oncologists to select the best drug for each patient. 相似文献
16.
Advances in cancer immunotherapy and a growing body of research have focused on the role of the antitumor response in breast cancer. Triple‐negative breast cancer (TNBC) is the most immunogenic breast cancer subtype, and there is strong evidence that tumor‐infiltrating lymphocytes in TNBC have prognostic value and are associated with clinical outcome and improved survival. Evading antitumor immunity is a hallmark for the development and progression of cancer. Immunotherapy studies have focused on the role of the programmed cell death‐1 (PD‐1) receptor/programmed death‐ligand 1 (PD‐L1) pathway in maintaining immunosuppression in the tumor microenvironment. Blockade of the PD‐1/PD‐L1 axis has emerged as a promising therapeutic option to enhance antitumor immunity and is actively being investigated in TNBC, with encouraging results. In this article, the authors review the current literature on checkpoint inhibitors in TNBC with a focus on PD‐1/PD‐L1 antibodies and discuss combination strategies and novel approaches for improving antitumor immunity and clinical outcome. Cancer 2018;124:2086‐103 . © 2018 American Cancer Society. 相似文献
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Shengxiang Ren Jifeng Feng Shenglin Ma HuaJun Chen Zhiyong Ma Cheng Huang Li Zhang Jianxing He Changli Wang Jianying Zhou Pongwut Danchaivijitr Chin-Chou Wang Ihor Vynnychenko Kai Wang Francisco Orlandi Virote Sriuranpong Ben Li Jun Ge Thao Dang Caicun Zhou 《International journal of cancer. Journal international du cancer》2023,153(3):623-634
KEYNOTE-033 (NCT02864394) was a multicountry, open-label, phase 3 study that compared pembrolizumab vs docetaxel in previously treated, programmed death-ligand 1 (PD-L1)-positive, advanced non-small cell lung cancer (NSCLC), with most patients enrolled in mainland China. Eligible patients were randomized (1:1) to pembrolizumab 2 mg/kg or docetaxel 75 mg/m2 every 3 weeks. Primary endpoints were overall survival (OS) and progression-free survival and were evaluated sequentially using stratified log-rank tests, first in patients with PD-L1 tumor proportion score (TPS) ≥50% and then in patients with PD-L1 TPS ≥1% (significance threshold: P < .025, one-sided). A total of 425 patients were randomized to pembrolizumab (N = 213) or docetaxel (N = 212) between 8 September 2016 and 17 October 2018. In patients with a PD-L1 TPS ≥50% (n = 227), median OS was 12.3 months with pembrolizumab and 10.9 months with docetaxel; the hazard ratio (HR) was 0.83 (95% confidence interval [CI]: 0.61-1.14; P = .1276). Because the significance threshold was not met, sequential testing of OS and PFS was ceased. In patients with a PD-L1 TPS ≥1%, the HR for OS for pembrolizumab vs docetaxel was 0.75 (95% CI: 0.60-0.95). In patients from mainland China (n = 311) with a PD-L1 TPS ≥1%, HR for OS was 0.68 (95% CI: 0.51-0.89). Incidence of grade 3 to 5 treatment-related AEs was 11.3% with pembrolizumab vs 47.5% with docetaxel. In summary, pembrolizumab improved OS vs docetaxel in previously treated, PD-L1-positive NSCLC without unexpected safety signals; although the statistical significance threshold was not reached, the numerical improvement is consistent with that previously observed for pembrolizumab in previously treated, advanced NSCLC. 相似文献
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Elisa Funck-Brentano Bouchra Baghad Magali Fort Iman Aouidad Anissa Roger Alain Beauchet Yves Otmezguine Astrid Blom Christine Longvert Blandine Boru Philippe Saiag 《International journal of cancer. Journal international du cancer》2020,147(6):1707-1714
Advanced melanoma patients who failed anti-PD-1 therapy have limited options. We analyzed a cohort of 133 advanced melanoma patients receiving anti-PD-1 monotherapy in a referral center between April 2015 and December 2017, and included the 26 patients with confirmed progressive (PD) or stable disease who received additional radiotherapy with an unmodified anti-PD-1 mAb regimen. Tumor evaluations were done on radiated and nonradiated (RECIST 1.1) lesions, with abscopal effect defined as a partial (PR) or complete response (CR) outside radiated fields. Primary endpoint was the CR + PR rate in radiated + nonradiated lesions. Secondary endpoints were progression-free survival (PFS), melanoma-specific survival (MSS) and safety. First late radiotherapy, consisting of hypofractionated radiotherapy (3–5 sessions, 20–26 Gy), standard palliative radiotherapy or brain radiosurgery was begun after a median of 6.3 months of anti-PD-1 in 23, 2 and 1 patient(s), respectively. Best response was 8 (31%) CR, 2 (8%) profound PR allowing surgical resection of remaining metastases and 16 (62%) PD. Abscopal effect was seen in 35% of patients. Median PFS and MSS since anti-PD-1 initiation was 15.2 [95% CI: 8.0 not achieved (na)] and 35.3 [95% CI: 18.5 na] months, respectively. PFS curves seemed to achieve a plateau. We discontinued anti-PD-1 therapy in 9/10 of patients with no residual evaluable disease and observed one relapse after a median of 10 months off anti-PD1-therapy. No unusual adverse event was recorded. Limitations of the study include its retrospective nature and limited size. Hypofractionated radiotherapy may enhance anti-PD1 monotherapy efficacy in patients who previously failed anti-PD-1 therapy. Controlled studies are needed. 相似文献
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Shaked Lev-Ari MD Michael Serzan MD Tianmin Wu MS Andrew Ip MD Lauren Pascual HSD Brittany Sinclaire MS Shari Adams HSD Michael Marafelias BS Lakshmi Ayyagari MD Sarvarinder K. Gill MD Barbara Ma MD Jacob P. Zaemes MD Alexandra Della Pia PharmD Adil Alaoui MS Subha Madhavan PhD Anas Belouali MS Andrew Pecora MD Jaeil Ahn PhD Michael B. Atkins MD Neil J. Shah MD 《Cancer》2023,129(12):1885-1894