scholarly journals Implementation of Double Immune Checkpoint Blockade Increases Response Rate to Induction Chemotherapy in Head and Neck Cancer

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1959
Author(s):  
Sabine Semrau ◽  
Antoniu-Oreste Gostian ◽  
Maximilian Traxdorf ◽  
Markus Eckstein ◽  
Sandra Rutzner ◽  
...  
Keyword(s):  
Head And Neck ◽  
Induction Chemotherapy ◽  
Immune Checkpoint ◽  
Response Rate ◽  
Locally Advanced ◽  
Young Patients ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Fixed Dose ◽  
Treatment Type

To determine whether a single dose of double immune checkpoint blockade (induction chemoimmunotherapy (ICIT)) adds benefit to induction single-cycle platinum doublet (induction chemotherapy (IC)) in locally advanced head and neck squamous cell carcinoma (HNSCC), patients treated with cisplatin 30 mg/m2 d1-3 and docetaxel 75 mg/m2 d1 combined with durvalumab 1500 mg fixed dose d5 and tremelimumab 75 mg fixed dose d5 (ICIT) within the CheckRad-CD8 trial were compared with a retrospective cohort receiving the same chemotherapy (IC) without immunotherapy. The endpoint of this analysis was the complete response rate (CR). A total of 53 patients were treated with ICIT and 104 patients with IC only. CR rates were 60.3% for ICIT and 40.3% for IC (p = 0.018). In the total population (n = 157), the most important predictor to achieve a CR was treatment type (OR: 2.21 for ICIT vs. IC; p = 0.038, multivariate analysis). The most diverse effects in CR rates between ICIT and IC were observed in younger (age ≤ 60) patients with HPV-positive OPSCCs (82% vs. 33%, p = 0.176), while there was no difference in older patients without HPV-positive OPSCCs (53% vs. 48%). The analysis provides initial evidence that ICIT could result in higher CR rates than IC. Young patients with HPV-positive OPSCCs may have the greatest benefit from additional immune checkpoint inhibitors.

A phase II study of chemotherapy and immune checkpoint blockade with pembrolizumab in the perioperative and maintenance treatment of locoregional gastric or GE junction adenocarcinoma.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. TPS197-TPS197
Author(s):  
Paul Eliezer Oberstein ◽  
Beth Schrope ◽  
Tamas Gonda ◽  
Amrita Sethi ◽  
Arnold Han ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Locally Advanced ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Standard Of Care ◽  
Cell Receptor ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Fixed Dose ◽  
Serum Samples

TPS197 Background: Gastric cancer is a prevalent worldwide disease for which surgical resection alone is insufficient to cure the majority of localized patients. Peri-operative chemotherapy is a standard of care approach that has demonstrated modest improved survival rates. Immune checkpoint therapy has proven efficacy in a subset of patients with refractory disease but it’s role in earlier stage disease and in combination with chemotherapy is not defined. By combining chemotherapy with immune checkpoint blockade utilizing pembrolizumab we hypothesize that we will obtain improved tumor response and prolonged disease control compared to chemotherapy alone. Tissue specimens will be obtained at baseline and at the time of surgery for novel correlative studies including single cell T cell receptor characterization and expression profiling. Methods: This Phase 2, multicenter study investigates the efficacy and safety of oxaliplatin/FU based chemotherapy plus pembrolizumab in the perioperative treatment of locally advanced, resectable gastric or GE junction adenocarcinoma. A total of 40 eligible patients with T2-4 and/or N1, M0 tumors on imaging or EUS will be treated with capecitabine, oxaliplatin and epirubicin (epirubicin can be omitted at investigator discretion) plus fixed dose pembrolizumab at 200mg for 3 cycles prior to surgery plus one additional dose of pembrolizumab alone before surgery. Following completion of post-operative chemotherapy with pembrolizumab, patients continue pembrolizumab for 1 year of maintenance therapy (17 cycles). The primary endpoint is disease free survival at 24 months (DFS 24) with an estimated 80% power to detect a clinically significant 24 month DFS rate of 65%. A key secondary endpoint is pathCR at surgery, additional endpoints include response rate (RECIST 1.1), 12 month DFS, and overall survival. Safety, including surgical outcomes, will be assessed. Multiple correlative analyses utilizing baseline and post-treatment tissue, PD-L1 staining, and serum samples will also be performed. Enrollment opened in March 2017. Clinical trial information: NCT02918162.

Response to docetaxel and cisplatin induction chemotherapy of locally advanced head and neck squamous cell carcinoma: a multicenter, non-comparative, open-label interventional pilot study

2016 ◽  
Vol 130 (9) ◽  
pp. 833-842 ◽  
Author(s):  
V Noronha ◽  
C Goswami ◽  
S Patil ◽  
A Joshi ◽  
V M Patil ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Pilot Study ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Response Rate ◽  
Locally Advanced ◽  
Comparable Efficacy ◽  
Induction Regimen

AbstractBackground:Docetaxel, cisplatin plus 5-fluorouracil is an efficacious induction regimen but is more toxic than cisplatin plus 5-fluorouracil. This study aimed to determine whether docetaxel and cisplatin without 5-fluorouracil maintains efficacy while decreasing toxicity.Methods:A multicenter non-comparative pilot study of locally advanced squamous cell carcinoma of the head and neck was performed. Patients received primary therapy comprising three cycles of 75 mg/m2 docetaxel and 75 mg/m2 cisplatin followed by concurrent chemoradiotherapy. The primary endpoint was the response rate to the docetaxel and cisplatin induction regimen.Results:A total of 26 patients were enrolled: of these, 23 (88.5 per cent) received all three docetaxel and cisplatin cycles. Common grade 3–4 adverse events were febrile neutropenia (19.2 per cent of patients), diarrhoea (19.2 per cent) and non-neutropenic infection (15.4 per cent). The overall response rate to docetaxel and cisplatin induction chemotherapy was 65.4 per cent. A total of 23 patients (88.5 per cent) subsequently received chemoradiotherapy with a median radiotherapy dose of 70 Gy. The response rate to chemoradiotherapy was 73 per cent. At a median follow up of 44 months, the 3-year progression-free survival and overall survival rates were 62 per cent and 69 per cent, respectively.Conclusion:Docetaxel and cisplatin induction chemotherapy is a feasible induction regimen with comparable efficacy to docetaxel, cisplatin and 5-fluorouracil induction chemotherapy.

Induction chemotherapy with docetaxel, cisplatin and cetuximab versus docetaxel, cisplatin and 5-fluorouracil followed by radiotherapy with cetuximab for locally advanced or inoperable squamous cell carcinoma of the head and neck: Promising results of a randomized phase II AGMT-trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6027-6027
Author(s):  
Felix Keil ◽  
Maximilian Hartl ◽  
Gabriela Altorjai ◽  
Martin Pecherstorfer ◽  
Beate Mayrbäurl ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Induction Chemotherapy ◽  
Phase Ii ◽  
Response Rate ◽  
Locally Advanced ◽  
Stage Iii ◽  
Randomized Phase Ii ◽  
Unresectable Stage

6027 Background: Induction chemotherapy (ICT) with Cisplatin (P), 5-FU (F) and Taxanes (T) is a therapeutical option in patients suffering from locally advanced or unresectable stage III or IV squamous cell carcinoma of the head and neck (SCCHN). The role of ICT is controversial and toxicity and/or delay of radiotherapy may reduce the potential benefit of this treatment regimen. Here we report promising results of a randomized phase II trial comparing TPF with TP and Cetuximab (C) replacing F. Methods: In our trial, N= 100 patients with locally advanced or unresectable stage III or IV SCCHN were randomly assigned to either Arm A ( N= 49), receiving TPF, or Arm B ( N= 51), receiving TPC, both followed by radiotherapy (RT) + C. The primary end-point of the study was overall response rate (ORR) three months after RT + C was finished. Results: We observed a remarkable response rate (CR + PR) of 86.4% in the TPC-arm that compared favorably with 77.5% responding patients in the TPF-arm three months after RT + C was completed. OS and PFS were similar in both arms. After 400 days we observed an OS rate of 79% in the TPF and 86% in the TPC arm, and a PFS rate of 67% in the TPF and 70% in the TPC arm. TPC containing ICT led to less serious adverse events (SAEs), including blood and lymphatic disorders (40.8% in TPF arm, 27.5% in TPC arm) and metabolism and nutrition disorders (22.4% in TPF arm, 9.8% in TPC arm) during ICT. Interestingly, in HPVp16 positive patients, 88.24% in the TPF-arm and 93.33% in the TPC-arm showed CR or PR three months after RT + C, whereas only 69.57% in the TPF-arm and 82.76% in the TPC-arm showed CR or PR. We only lost one patient because of treatment-related mortality (TRM) and no delay from the end of ICT to local radiotherapy was observed in any patient. All patients received RT + C within three weeks after ICT was completed. Conclusions: In conclusion, TPC is a feasible and tolerable therapy regimen and can be applied within one day with less hematological toxicities. In contrast, more local reactions were observed after TPC. TPC containing ICT leads to improved response rates, while OS and PFS were similar in both arms. TRM was extremely low with 1%. Therefore, we conclude, that TPC containing ICT could be a considerable therapeutical alternative for patients with locally advanced or unresectable stage III or IV SCCHN, who are eligible for ICT. Clinical trial information: 2011-005540-99.

Chemo4MetPanc: A phase II study with combination chemotherapy (gemcitabine and nab-paclitaxel), chemokine (C-X-C) motif receptor 4 inhibitor (motixafortide), and immune checkpoint blockade (cemiplimab) in metastatic treatment naïve pancreas adenocarcinoma (PDAC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS454-TPS454
Author(s):  
Ilenia Pellicciotta ◽  
Emily Linda Alouani ◽  
Alexander Raufi ◽  
Samuel M Pan ◽  
Jianhua Hu ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Response Rate ◽  
Treatment Options ◽  
The United States ◽  
Neoplastic Cell ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Open Label ◽  
Pancreas Adenocarcinoma ◽  
Treatment Naïve

TPS454 Background: Pancreas adenocarcinoma (PDAC) is an aggressive cancer projected to be the second leading cause of cancer-related death in the United States by 2030 for which improved treatment options are desperately needed. Immune checkpoint blockade (ICB) for PDAC has failed as monotherapy in early phase clinical trials likely due to a highly immunosuppressive tumor microenvironment. The CXCR4/CXCL12 axis is a key immune evasion mechanism thought to deter CD8+ T-cells (CTLs) from infiltrating the tumor. We performed a large seven arm survival and biopsy/necropsy study in KPC mice (KrasLSL.G12D/+;p53R172H/+;Pdx1Cretg/+) where we demonstrate that addition of gemcitabine to CXCR4 inhibition in combination with ICB, enhanced tumor stabilization and neoplastic cell death, and improved survival by 50 percent. Multiplex immunofluorescence indicated an increased CTL to regulatory T-cell ratio and clustering of CTLs around neoplastic cells. Presented here is a trial-in progress that will evaluate combination of a CXCR4 inhibitor, ICB, and chemotherapy in treatment naïve patients with PDAC. Methods: This is a multicenter, single arm, open-label phase 2 study of combination motixafortide 1.25mg/kg SC monotherapy for 5 days during priming followed by twice weekly, cemiplimab 350mg IV once every 21 days, gemcitabine 1000mg/m2 IV with nab-paclitaxel 125mg/m2 IV on days 1, 8, and 15 every 28 days. Patients with histologically confirmed metastatic PDAC who have not received prior therapy will be enrolled. The primary endpoint is overall response rate by 16 weeks. A response rate greater than 45% by 16 weeks is considered promising, whereas a response rate of less than 23% is considered not promising. We will use a Simon optimal 2-stage design, where we will enroll 10 patients in the first stage. If 3 or more patients meet the endpoint in the first stage, the study will be expanded to a total of 40 patients. If a total of 14 or more patients achieve CR or PR by 16 weeks, the agent will be considered promising and worthy of further study. Secondary endpoints include safety, mPFS, disease control rate (DCR), and mOS. Correlative aims include analyses of pre- and on-treatment biopsies with quantitative multiplex immunofluorescence, RNA-sequencing, and generation of patient derived organoids for association with clinical benefit and to determine mechanisms of action/resistance. An interim analysis will be performed at the conclusion of the stage I portion of the study. Clinical trial information: NCT04543071.

Immunotherapy of head and neck squamous cell carcinoma (HNSCC). Immune checkpoint blockade

2018 ◽  
Vol 72 (4) ◽  
pp. 1-5 ◽  
Author(s):  
Krzysztof Przybylski ◽  
Ewa Majchrzak ◽  
Liucija Weselik ◽  
Wojciech Golusiński
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Neck Squamous Cell Carcinoma

Leczenie chorych na raka płaskonabłonkowego głowy i szyi jest istotnym problemem. Obserwuje się wzrost zachorowalności na nowotwory złośliwe tego regionu. Chirurgia, radioterapia oraz chemioterapia często nie są wystarczającymi metodami leczenia. Dokładna analiza procesów zachodzących w mikrośrodowisku guza pozwoliła na wyodrębnienie trzech etapów składających się na reakcję organizmu człowieka na wrogie antygeny, jakimi są antygeny nowotworowe. Poznanie tych mechanizmów skutkowało wprowadzeniem nowego terminu immunoonkologia. Jest to dziedzina leczenia nowotworów skupiająca się na wykorzystaniu układu immunologicznego pacjenta w celu zwalczania choroby. Immunoterapia u chorych na raka przyniosła pozytywne efekty. Wykorzystanie inhibitorów immunologicznych punktów kontroli, jak przeciwciała monoklonalne przeciwko receptorowi CTLA – 4 oraz PD – 1 umożliwiło modulację funkcji limfocytów T w konsekwencji znosząc immunosupresję w mikrośrodowisku guza. Przeprowadzono badania kliniczne z zastosowaniem nivolumabu oraz ipilimumabu, które potwierdziły ich przydatność kliniczną. Zatwierdzenie przez FDA nivolumabu w leczeniu nawrotowego i przerzutowego raka płaskonabłonkowego głowy i szyi wydłużyło całkowity czas przeżycia chorych oraz czas przeżycia wolny od choroby. Dane statystyczne wskazują na przewagę immunoterapii nad innymi metodami leczenia w zaawansowanym stadium choroby nowotworowej. Celem pracy jest omówienie podstawowych zagadnień związanych z immunoterapią, w szczególności immunoterapią u chorych na raka płaskonabłonkowego głowy i szyi.

Chemotherapy after immune checkpoint blockade in patients with recurrent, metastatic squamous cell carcinoma of the head and neck

Oral Oncology ◽  
2020 ◽  
Vol 105 ◽  
pp. 104676 ◽  
Author(s):  
Alec J. Kacew ◽  
Ethan J. Harris ◽  
Jochen H. Lorch ◽  
Jonathan D. Schoenfeld ◽  
Danielle N. Margalit ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Metastatic Squamous Cell Carcinoma
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