scholarly journals PD (L) 1-Inhibitors and Radiation: A Good Combination for Local and Systemic Effects?

2021 ◽  
Vol 9 (6) ◽  
Author(s):  
Gunther Klautke ◽  
Klaus Pietschmann ◽  
Zohier Srour
Keyword(s):  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Point Of View ◽  
Solid Tumours ◽  
Abscopal Effect ◽  
Stereotactic Radiation ◽  
Fractionated Radiotherapy ◽  
Treatment Situation ◽  
Concurrent Applications ◽  
Conventionally Fractionated

Radiation therapy is an important component in treatment of solid tumours, in a locally advanced situation and also in a metastatic situation. Indications for using PD- (L) -1 inhibitors increase especially in the metastatic situation, but also in locally advanced solid tumours. Preclinical data show local and systemically effective synergies between local irradiation and an application of checkpoint inhibitors. In the metastatic situation, a possible abscopal effect is of particular interest. This abscopal effect can be achieved especially in concurrent approaches of PD-(L)-1-inhibitors and stereotactic radiation with higher single doses like 3 x 8 Gy or 4 x 12,5 Gy. In locally advanced tumours a local enhancement of the radiation effect, and also an abscopal effect to eliminate potential micrometastases to is of great interest to achieve healing. In this treatment situation promising results are seen in the application of PD-(L)-1-inhibitors as maintenance after concurrent chemoradiation especially in non-small cell lung cancer, as well as in concurrent applications of conventionally fractionated radiotherapy and PD-(L)-1 inhibitors. These approaches and results are considered from the clinician’s point of view.

scholarly journals Induction Chemotherapy Followed By Concurrent Chemoradiotherapy Versus Radiotherapy Alone In Locally Advanced HNSCC – An Experience From Medical College In West Bengal, India

2016 ◽  
Vol 3 (2) ◽  
Author(s):  
Dr. Partha Dasgupta ◽  
Dr. Santanu Acharyya ◽  
Dr. Debangshu Bhanja Choudhury ◽  
Dr. Amitabha Chakrabarty ◽  
Dr. Kakali Choudhury ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Locally Advanced ◽  
Response Assessment ◽  
Definitive Treatment ◽  
Public Health Issue ◽  
P Value ◽  
Fractionated Radiotherapy ◽  
Medical College ◽  
Late Morbidity ◽  
Conventionally Fractionated

<p><strong>Introduction:</strong></p><p>Locally advanced Head and neck cancers (LAHNSCCs) are emerging as an important public health issue in India. Our study was designed to provide NACT to LAHNSCC patients followed by comparison between chemoradiation versus only radiation in rural medical college.</p><p><strong>Material and Method: </strong></p><p>Histopathologically proven non-metastatic LAHNSCC were randomized into 2 arms. Patients in both arms initially received 3 cycles of NACT (inj Paclitaxel 175mg/m2 and inj Carboplation AUC 6, i.v, q 21 days). Thereafter they received definitive treatment accordingly: arm A (control arm) received conventionally fractionated radiotherapy (CFRT), 70 Gy in 35 # and in arm B (study arm) received conventionally fractionated radiotherapy (CFRT), 70 Gy in 35 # with concomitant 3 weekly cisplatin 100mg/m2. A RECIST v1.0 criterion was used for response assessment and toxicities evaluated by RTOG Acute and late Morbidity scorings.</p><p><strong>Results: </strong></p><p>Between July 2013 to December 2015, 140 patients were randomized into arms. Laryngeal and hypopharyngeal subsites together accounted for 36.4% patients. 70% of patients were in AJCC TNM 7th edition stage IV. 87.8% of patients completed the planned 3 cycles of NACT. Response assessment using RECIST v1.0 criteria after NACT were comparable in both arms with CR in 25% patients and PR in another 60% patients, p value 0.963. After completion of full treatment, 68.57% (48/70) patients in concurrent arm had CR against 55.72% patients (39/70) in only radiation arm, p value 0.241. At the end of study, 38 patients in arm A and 46 patients in arm B were eligible for response assessment. 24 patients (63.2%) in arm A were in complete response against 32 patients (69.6%) in concurrent chemoradiation arm, p value 0.535. Gastrointestinal and mucositis grade 3 toxicities were significantly increased in concomitant chemoradiation arm.</p><p><strong>Conclusion: </strong></p><p>Our study failed to show any statistical significant improvement in CR in favour of CTRT arm in our subset of patients. Yet definitive conclusion regarding use of only radiation cannot be made for LAHNSCC especially when combined with induction chemotherapy.</p>

scholarly journals Nonclinical Development of SRK-181: An Anti-Latent TGFβ1 Monoclonal Antibody for the Treatment of Locally Advanced or Metastatic Solid Tumors

2021 ◽  
pp. 109158182199894
Author(s):  
Brian T. Welsh ◽  
Ryan Faucette ◽  
Sanela Bilic ◽  
Constance J. Martin ◽  
Thomas Schürpf ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Checkpoint Inhibitors ◽  
Human Peripheral Blood ◽  
Phase 1 ◽  
Locally Advanced ◽  
Acquired Resistance ◽  
Transforming Growth Factor Β ◽  
Human Antibody ◽  
Primary Resistance

Checkpoint inhibitors offer a promising immunotherapy strategy for cancer treatment; however, due to primary or acquired resistance, many patients do not achieve lasting clinical responses. Recently, the transforming growth factor-β (TGFβ) signaling pathway has been identified as a potential target to overcome primary resistance, although the nonselective inhibition of multiple TGFβ isoforms has led to dose-limiting cardiotoxicities. SRK-181 is a high-affinity, fully human antibody that selectively binds to latent TGFβ1 and inhibits its activation. To support SRK-181 clinical development, we present here a comprehensive preclinical assessment of its pharmacology, pharmacokinetics, and safety across multiple species. In vitro studies showed that SRK-181 has no effect on human platelet function and does not induce cytokine release in human peripheral blood. Four-week toxicology studies with SRK-181 showed that weekly intravenous administration achieved sustained serum exposure and was well tolerated in rats and monkeys, with no treatment-related adverse findings. The no-observed-adverse-effect levels levels were 200 mg/kg in rats and 300 mg/kg in monkeys, the highest doses tested, and provide a nonclinical safety factor of up to 813-fold (based on Cmax) above the phase 1 starting dose of 80 mg every 3 weeks. In summary, the nonclinical pharmacology, pharmacokinetic, and toxicology data demonstrate that SRK-181 is a selective inhibitor of latent TGFβ1 that does not produce the nonclinical toxicities associated with nonselective TGFβ inhibition. These data support the initiation and safe conduct of a phase 1 trial with SRK-181 in patients with advanced cancer.

624 A PHASE III STUDY ON NEOADJUVANT TORIPALIMAB PLUS CHEMOTHERAPY VERSUS NEOADJUVANT CHEMOTHERAPY FOR LOCALLY RESECTABLE ESOPHAGEAL SQUAMOUS CELL CARCINOMA

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Yan Zheng ◽  
Jiangong Zhang ◽  
Wenqun Xing
Keyword(s):  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
R0 Resection ◽  
Phase Iii Trial ◽  
Free Survival

Abstract   In recent years, immune checkpoint inhibitors (ICIs) have shown promising results in the treatment of ESCC. More than 20 phase II clinical trials have been launched to explore combinations of ICIs in the neoadjuvant setting for ESCC. Based on our phase II clinical trial, a two-arm phase III trial was launched in our Hospital. Methods A two-arm phase III trial was launched in April 2020 in our Hospital. Patient recruitment will be completed within 18 months. The primary endpoint is event-free survival (EFS). The secondary endpoints include pathologic complete response (pCR), disease-free survival (DFS) rate, overall response rate (ORR), R0 resection rate, major pathologic response (MPR), adverse events (AEs), complication rate and quality of life (QOL). A biobank of pretreatment, resected tumor tissue and paired blood samples will be built for translational research in the future. Results Until Dec. 2021, one hundred and twenty ESCC patients recruited in the trial. The trial is ongoing. Conclusion This RCT directly compares NAC with neoadjuvant toripalimab plus chemotherapy in terms of EFS for locally advanced ESCC. The results may usher in a new era of resectable ESCC treatment.

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