Preoperative durvalumab (D) with or without tremelimumab (T) for resectable head and neck squamous cell carcinoma (HNSCC): Updated results with high dimensional profiling of circulating immune cells
6072 Background: Although PD-1 blockade has improved survival in patients with recurrent and/or metastatic HNSCC, safety and efficacy of neoadjuvant immunotherapy with PD-L1 inhibitor with or without CTLA-4 inhibitor has not been investigated. Here, we report the updated results of the safety and ef...
Saved in:
Published in | Journal of clinical oncology Vol. 40; no. 16_suppl; p. 6072 |
---|---|
Main Authors | , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
01.06.2022
|
Online Access | Get full text |
Cover
Loading…
Abstract | 6072
Background: Although PD-1 blockade has improved survival in patients with recurrent and/or metastatic HNSCC, safety and efficacy of neoadjuvant immunotherapy with PD-L1 inhibitor with or without CTLA-4 inhibitor has not been investigated. Here, we report the updated results of the safety and efficacy of a preoperative D with or without T (D+/-T) in patients with resectable HNSCC, accompanied with high dimensional profiling of circulating immune cells. Methods: Patients with locally advanced but resectable HNSCC were eligible. Enrolled patients were randomized into D or D+T, stratified by primary site and human papilloma virus (HPV) infection status. A single dose of preoperative D (1500mg) or D+T (1500mg+75mg) was administered, with surgery planned 2 to 8 weeks later for curative resection. Postoperative (chemo) radiation was prescribed based on standard guidelines, followed by maintenance with D every 4 weeks for 1 year. Dynamic changes in circulating immune cells were tracked with mass cytometry. The primary objective was to determine the local recurrence rate. Secondary endpoints included pathologic response, safety, survival outcome, and exploration of immune dynamics. Results: As of January 25th 2022 for the interim analysis, a total of 45 patients were completely enrolled and received surgical resection (D: 21 patients, D+T: 24 patients). Oropharyngeal cancer was most common (n = 23; 51.1%) and HPV-mediated cancer was observed in 20 patients (44.4%). Neoadjuvant D+/-T had acceptable safety profiles and was not associated with delays in surgery or unexpected adverse events. Tumor shrinkage was observed in 31 patients (68.9%), with 15.6% of average tumor shrinkage (range; 100.0% to -80.0%). Major pathologic response (no more than 10% of viable tumor cells) was achieved in 3 patients (6.7%), including 2 cases with pathologic complete response (4.4%). During median follow-up duration of 407 days after surgery, local recurrence and systemic recurrence were documented in 9 patients (20.0%) and 7 patients (15.6%), respectively. Median disease-free survival and overall survival was 910 days and not reached, respectively. High dimensional immune profiling with mass cytometry revealed that D+T disproportionally increased the frequency of regulatory T cells accompanied with the upregulation of their functional markers, which was absent in patients treated with D monotherapy. Conclusions: These updated data suggested that preoperative D+/-T was safe and feasible and had the potential to provide clinical benefits for patients with resectable HNSCC. Distinct immunologic changes in circulating immune cells were induced by each treatment regimen, warranting further investigation. The trial is ongoing and the updated outcomes with immune correlates will be presented in this ASCO. Clinical trial information: NCT03737968. |
---|---|
AbstractList | 6072
Background: Although PD-1 blockade has improved survival in patients with recurrent and/or metastatic HNSCC, safety and efficacy of neoadjuvant immunotherapy with PD-L1 inhibitor with or without CTLA-4 inhibitor has not been investigated. Here, we report the updated results of the safety and efficacy of a preoperative D with or without T (D+/-T) in patients with resectable HNSCC, accompanied with high dimensional profiling of circulating immune cells. Methods: Patients with locally advanced but resectable HNSCC were eligible. Enrolled patients were randomized into D or D+T, stratified by primary site and human papilloma virus (HPV) infection status. A single dose of preoperative D (1500mg) or D+T (1500mg+75mg) was administered, with surgery planned 2 to 8 weeks later for curative resection. Postoperative (chemo) radiation was prescribed based on standard guidelines, followed by maintenance with D every 4 weeks for 1 year. Dynamic changes in circulating immune cells were tracked with mass cytometry. The primary objective was to determine the local recurrence rate. Secondary endpoints included pathologic response, safety, survival outcome, and exploration of immune dynamics. Results: As of January 25th 2022 for the interim analysis, a total of 45 patients were completely enrolled and received surgical resection (D: 21 patients, D+T: 24 patients). Oropharyngeal cancer was most common (n = 23; 51.1%) and HPV-mediated cancer was observed in 20 patients (44.4%). Neoadjuvant D+/-T had acceptable safety profiles and was not associated with delays in surgery or unexpected adverse events. Tumor shrinkage was observed in 31 patients (68.9%), with 15.6% of average tumor shrinkage (range; 100.0% to -80.0%). Major pathologic response (no more than 10% of viable tumor cells) was achieved in 3 patients (6.7%), including 2 cases with pathologic complete response (4.4%). During median follow-up duration of 407 days after surgery, local recurrence and systemic recurrence were documented in 9 patients (20.0%) and 7 patients (15.6%), respectively. Median disease-free survival and overall survival was 910 days and not reached, respectively. High dimensional immune profiling with mass cytometry revealed that D+T disproportionally increased the frequency of regulatory T cells accompanied with the upregulation of their functional markers, which was absent in patients treated with D monotherapy. Conclusions: These updated data suggested that preoperative D+/-T was safe and feasible and had the potential to provide clinical benefits for patients with resectable HNSCC. Distinct immunologic changes in circulating immune cells were induced by each treatment regimen, warranting further investigation. The trial is ongoing and the updated outcomes with immune correlates will be presented in this ASCO. Clinical trial information: NCT03737968. |
Author | Jung, Inkyung Park, Heejung Hong, Min Hee Cho, Byoung Chul Kim, Da Hee Koh, Yoon Woo Bang, Yoon Ji Park, Young Min Kim, Hyun Je Kim-Schulze, Seunghee Lee, Brian Kim, Jae Hwan Merad, Miriam Park, Goeun Kim, Se-Heon Lim, Sun Min Kim, Hye Ryun Pyo, Kyoung-Ho Kim, Chang Gon |
Author_xml | – sequence: 1 givenname: Chang Gon surname: Kim fullname: Kim, Chang Gon organization: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea – sequence: 2 givenname: Min Hee surname: Hong fullname: Hong, Min Hee organization: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea – sequence: 3 givenname: Da Hee surname: Kim fullname: Kim, Da Hee organization: Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, South Korea – sequence: 4 givenname: Sun Min surname: Lim fullname: Lim, Sun Min organization: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea – sequence: 5 givenname: Brian surname: Lee fullname: Lee, Brian organization: Genome Medicine Institute, Seoul National University College of Medicine, Seoul, South Korea – sequence: 6 givenname: Yoon Ji surname: Bang fullname: Bang, Yoon Ji organization: Deparment of Biomedical Science, Seoul National University College of Medicine, Seoul, South Korea – sequence: 7 givenname: Se-Heon surname: Kim fullname: Kim, Se-Heon organization: Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, South Korea – sequence: 8 givenname: Young Min surname: Park fullname: Park, Young Min organization: Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, South Korea – sequence: 9 givenname: Kyoung-Ho surname: Pyo fullname: Pyo, Kyoung-Ho organization: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea – sequence: 10 givenname: Jae Hwan surname: Kim fullname: Kim, Jae Hwan organization: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea – sequence: 11 givenname: Heejung surname: Park fullname: Park, Heejung organization: Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea – sequence: 12 givenname: Goeun surname: Park fullname: Park, Goeun organization: Division of Biostatics, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, South Korea – sequence: 13 givenname: Inkyung surname: Jung fullname: Jung, Inkyung organization: Division of Biostatics, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, South Korea – sequence: 14 givenname: Seunghee surname: Kim-Schulze fullname: Kim-Schulze, Seunghee organization: Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY – sequence: 15 givenname: Miriam surname: Merad fullname: Merad, Miriam organization: Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY – sequence: 16 givenname: Byoung Chul surname: Cho fullname: Cho, Byoung Chul organization: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea – sequence: 17 givenname: Hyun Je surname: Kim fullname: Kim, Hyun Je organization: Genome Medicine Institute, Seoul National University College of Medicine, Seoul, South Korea – sequence: 18 givenname: Yoon Woo surname: Koh fullname: Koh, Yoon Woo organization: Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, South Korea – sequence: 19 givenname: Hye Ryun surname: Kim fullname: Kim, Hye Ryun organization: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea |
BookMark | eNotkc1uFDEQhC0UJDaBd2hu2cMstmft2eWGhp-AIoJEInEbeex21uCfwR4H8YI8F7PZnEpV3apu6TsnZzFFJOQ1oxvGKX3zpb_ZcMr5ZrsEcih1mvxG0o4_IysmeNd0nRBnZEW7ljds1_54Qc5L-Ukp2-5asSL_vmVME2Y1uwcEU_OD8jWoES7fr-GPmw-Q8qOmOsOcMaB34bRwuwa7DDMW1LMaPcIBlQEVDUTUv6D8riqkWkCj96BV1i6moODy6uv3vl-_hbvJqBnNsaH6uZzOHdz9AYwLGItLUXmYcrLOu3gPyYJ2WVe_PLtYF0KN-NheXpLnVvmCr570gtx9_HDbXzXXN58-9--uG82o5I3SvGuF1pZrtCj21iyOdkqhZjuuuR07LfcURzVKI_dCcsGENdKIbmulYe0F2Z96dU6lZLTDlF1Q-e_A6HAEMixAhiOQYbsET0CGI5D2P3VBiMg |
CitedBy_id | crossref_primary_10_1016_j_amjoto_2023_103985 |
ContentType | Journal Article |
DBID | AAYXX CITATION |
DOI | 10.1200/JCO.2022.40.16_suppl.6072 |
DatabaseName | CrossRef |
DatabaseTitle | CrossRef |
DatabaseTitleList | CrossRef |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Medicine Pharmacy, Therapeutics, & Pharmacology |
EISSN | 1527-7755 |
EndPage | 6072 |
ExternalDocumentID | 10_1200_JCO_2022_40_16_suppl_6072 |
GroupedDBID | --- .55 0R~ 18M 2WC 34G 39C 4.4 53G 5GY 5RE 8F7 AAQQT AARDX AAWTL AAYEP AAYXX ABJNI ABOCM ACGFO ACGFS ACGUR ADBBV AEGXH AENEX AIAGR ALMA_UNASSIGNED_HOLDINGS AWKKM BAWUL C45 CITATION CS3 DIK EBS EJD F5P F9R FBNNL FD8 GX1 H13 HZ~ IH2 IPNFZ K-O KQ8 L7B LSO MJL N9A O9- OK1 OVD OWW P2P QTD R1G RHI RIG RLZ RUC SJN SV3 TEORI TR2 TWZ UDS VVN WH7 X7M YCJ YFH YQY |
ID | FETCH-LOGICAL-c1062-ac2735ccf2cefe59fd35c07aaec182c2fb7c690ebab6d69562515fd6d574f6d13 |
ISSN | 0732-183X |
IngestDate | Fri Aug 23 04:09:24 EDT 2024 |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 16_suppl |
Language | English |
LinkModel | OpenURL |
MergedId | FETCHMERGED-LOGICAL-c1062-ac2735ccf2cefe59fd35c07aaec182c2fb7c690ebab6d69562515fd6d574f6d13 |
PageCount | 1 |
ParticipantIDs | crossref_primary_10_1200_JCO_2022_40_16_suppl_6072 |
PublicationCentury | 2000 |
PublicationDate | 2022-06-01 |
PublicationDateYYYYMMDD | 2022-06-01 |
PublicationDate_xml | – month: 06 year: 2022 text: 2022-06-01 day: 01 |
PublicationDecade | 2020 |
PublicationTitle | Journal of clinical oncology |
PublicationYear | 2022 |
SSID | ssj0014835 |
Score | 2.442415 |
Snippet | 6072
Background: Although PD-1 blockade has improved survival in patients with recurrent and/or metastatic HNSCC, safety and efficacy of neoadjuvant... |
SourceID | crossref |
SourceType | Aggregation Database |
StartPage | 6072 |
Title | Preoperative durvalumab (D) with or without tremelimumab (T) for resectable head and neck squamous cell carcinoma (HNSCC): Updated results with high dimensional profiling of circulating immune cells |
Volume | 40 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3db9MwELe2IU28IBggPqdDQlOrLF2aOcnCG2qB8rGt0lqpb1FiO1LFmpSkeRh_IH8XPtv5YDABe0kTy7kkul_t8_nud4S89lIax77D7cRzUpt68iw8YZ7tM0YFp06acMX2eeZP5vTTwltsbe93opaqTTJg3_-YV3Ibrco2qVfMkv0PzTZCZYM8l_qVR6lhefwnHU8Lka-F4e7mVYHM3as4QatxjMt95WTNC_WL8ccbdAZeLld1pxl2wjhDzEFiG5VFJQdnxd5qZYJ9tcpvVYzOAQsd_EhjzZZZvorx5snZxWgkBaBPYb5GxwEmwpTVZZ0xh0zIFsfqAZr5w9L1wU2YNVsWTJUOw5waTFIR6hnlDdZyk8GZZ-yXnQBTDlplSVgf2qCCiYk1PlVkXuJa93HcbfyiGy-qDLt3HSFyDd0EbJnxMjh2bTlCLfTUZsZzN5ALCM0EXA_4mh-qBrYflVg_tTOI-46uJmQMgvryt8nG1XW0R-cDfJ0BlU1G2KAV0SX4vjbxNuGQuBBzcVdxdB6hqIjKBiMqQlHb5I4bhB6GrI4_fm52yeiJLiBbf_gueWXe6-jGt-rYXx1Danaf3DM6hbcazg_Ilsj2yO6pifHYIwdTzaZ-dQizNjmwPIQDmLY861cPyY8u_KGFP_TGfUAEQl6AgT50oQ-9WR8k7KGFPSDsQcIeEPZQwx4QktDAHnoK9P03YAAPBvD6cQh46AAeGsBDnkIH8KABr6SXj8j8_bvZaGKbsiQ2Gzq-a8dMmvweY6nLRCq8MOXyygniWDC5WGdumgTMDx2RxInP_RA9DEMv5T73Apr6fHj8mOxkeSaeEAg4T1go0iF3KI0FTVx2QkPmS4NxGMrp_ylxa2VFa80-E_0VLM9uc9Nzcrf9T70gO5uiEi-lub1J9hXmfgLxBtoX |
link.rule.ids | 315,786,790,27955,27956 |
linkProvider | Flying Publisher |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Preoperative+durvalumab+%28D%29+with+or+without+tremelimumab+%28T%29+for+resectable+head+and+neck+squamous+cell+carcinoma+%28HNSCC%29%3A+Updated+results+with+high+dimensional+profiling+of+circulating+immune+cells&rft.jtitle=Journal+of+clinical+oncology&rft.au=Kim%2C+Chang+Gon&rft.au=Hong%2C+Min+Hee&rft.au=Kim%2C+Da+Hee&rft.au=Lim%2C+Sun+Min&rft.date=2022-06-01&rft.issn=0732-183X&rft.eissn=1527-7755&rft.volume=40&rft.issue=16_suppl&rft.spage=6072&rft.epage=6072&rft_id=info:doi/10.1200%2FJCO.2022.40.16_suppl.6072&rft.externalDBID=n%2Fa&rft.externalDocID=10_1200_JCO_2022_40_16_suppl_6072 |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0732-183X&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0732-183X&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0732-183X&client=summon |