دورية أكاديمية
Safety and Clinical Activity of Pembrolizumab and Multisite Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors.
| العنوان: | Safety and Clinical Activity of Pembrolizumab and Multisite Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors. |
|---|---|
| المؤلفون: | Luke JJ; Jason J. Luke, Jeffrey M. Lemons, Theodore G. Karrison, Sean P. Pitroda, James M. Melotek, Yuanyuan Zha, Hania A. Al-Hallaq, Ainhoa Arina, Nikolai N. Khodarev, Linda Janisch, Paul Chang, Jyoti D. Patel, Gini F. Fleming, John Moroney, Manish R. Sharma, Mark J. Ratain, Thomas F. Gajewski, Ralph R. Weichselbaum, and Steven J. Chmura, The University of Chicago, Chicago, IL; Julia R. White, The Ohio State University, Columbus, OH., Lemons JM; Jason J. Luke, Jeffrey M. Lemons, Theodore G. Karrison, Sean P. Pitroda, James M. Melotek, Yuanyuan Zha, Hania A. Al-Hallaq, Ainhoa Arina, Nikolai N. Khodarev, Linda Janisch, Paul Chang, Jyoti D. Patel, Gini F. Fleming, John Moroney, Manish R. Sharma, Mark J. Ratain, Thomas F. Gajewski, Ralph R. Weichselbaum, and Steven J. Chmura, The University of Chicago, Chicago, IL; Julia R. White, The Ohio State University, Columbus, OH., Karrison TG; Jason J. Luke, Jeffrey M. Lemons, Theodore G. Karrison, Sean P. Pitroda, James M. Melotek, Yuanyuan Zha, Hania A. Al-Hallaq, Ainhoa Arina, Nikolai N. Khodarev, Linda Janisch, Paul Chang, Jyoti D. Patel, Gini F. Fleming, John Moroney, Manish R. Sharma, Mark J. Ratain, Thomas F. Gajewski, Ralph R. Weichselbaum, and Steven J. Chmura, The University of Chicago, Chicago, IL; Julia R. White, The Ohio State University, Columbus, OH., Pitroda SP; Jason J. Luke, Jeffrey M. Lemons, Theodore G. Karrison, Sean P. Pitroda, James M. Melotek, Yuanyuan Zha, Hania A. Al-Hallaq, Ainhoa Arina, Nikolai N. Khodarev, Linda Janisch, Paul Chang, Jyoti D. Patel, Gini F. Fleming, John Moroney, Manish R. Sharma, Mark J. Ratain, Thomas F. Gajewski, Ralph R. Weichselbaum, and Steven J. Chmura, The University of Chicago, Chicago, IL; Julia R. White, The Ohio State University, Columbus, OH., Melotek JM; Jason J. Luke, Jeffrey M. Lemons, Theodore G. Karrison, Sean P. Pitroda, James M. Melotek, Yuanyuan Zha, Hania A. Al-Hallaq, Ainhoa Arina, Nikolai N. Khodarev, Linda Janisch, Paul Chang, Jyoti D. Patel, Gini F. Fleming, John Moroney, Manish R. Sharma, Mark J. Ratain, Thomas F. Gajewski, Ralph R. Weichselbaum, and Steven J. Chmura, The University of Chicago, Chicago, IL; Julia R. White, The Ohio State University, Columbus, OH., Zha Y; Jason J. Luke, Jeffrey M. Lemons, Theodore G. Karrison, Sean P. Pitroda, James M. Melotek, Yuanyuan Zha, Hania A. Al-Hallaq, Ainhoa Arina, Nikolai N. Khodarev, Linda Janisch, Paul Chang, Jyoti D. Patel, Gini F. Fleming, John Moroney, Manish R. Sharma, Mark J. Ratain, Thomas F. Gajewski, Ralph R. Weichselbaum, and Steven J. Chmura, The University of Chicago, Chicago, IL; Julia R. White, The Ohio State University, Columbus, OH., Al-Hallaq HA; Jason J. Luke, Jeffrey M. Lemons, Theodore G. Karrison, Sean P. Pitroda, James M. Melotek, Yuanyuan Zha, Hania A. Al-Hallaq, Ainhoa Arina, Nikolai N. Khodarev, Linda Janisch, Paul Chang, Jyoti D. Patel, Gini F. Fleming, John Moroney, Manish R. Sharma, Mark J. Ratain, Thomas F. Gajewski, Ralph R. Weichselbaum, and Steven J. Chmura, The University of Chicago, Chicago, IL; Julia R. White, The Ohio State University, Columbus, OH., Arina A; Jason J. Luke, Jeffrey M. Lemons, Theodore G. Karrison, Sean P. Pitroda, James M. Melotek, Yuanyuan Zha, Hania A. Al-Hallaq, Ainhoa Arina, Nikolai N. Khodarev, Linda Janisch, Paul Chang, Jyoti D. Patel, Gini F. Fleming, John Moroney, Manish R. Sharma, Mark J. Ratain, Thomas F. Gajewski, Ralph R. Weichselbaum, and Steven J. Chmura, The University of Chicago, Chicago, IL; Julia R. White, The Ohio State University, Columbus, OH., Khodarev NN; Jason J. Luke, Jeffrey M. Lemons, Theodore G. Karrison, Sean P. Pitroda, James M. Melotek, Yuanyuan Zha, Hania A. Al-Hallaq, Ainhoa Arina, Nikolai N. Khodarev, Linda Janisch, Paul Chang, Jyoti D. Patel, Gini F. Fleming, John Moroney, Manish R. Sharma, Mark J. Ratain, Thomas F. Gajewski, Ralph R. Weichselbaum, and Steven J. Chmura, The University of Chicago, Chicago, IL; Julia R. White, The Ohio State University, Columbus, OH., Janisch L; Jason J. Luke, Jeffrey M. Lemons, Theodore G. Karrison, Sean P. Pitroda, James M. Melotek, Yuanyuan Zha, Hania A. Al-Hallaq, Ainhoa Arina, Nikolai N. Khodarev, Linda Janisch, Paul Chang, Jyoti D. Patel, Gini F. Fleming, John Moroney, Manish R. Sharma, Mark J. Ratain, Thomas F. Gajewski, Ralph R. Weichselbaum, and Steven J. Chmura, The University of Chicago, Chicago, IL; Julia R. White, The Ohio State University, Columbus, OH., Chang P; Jason J. Luke, Jeffrey M. Lemons, Theodore G. Karrison, Sean P. Pitroda, James M. Melotek, Yuanyuan Zha, Hania A. Al-Hallaq, Ainhoa Arina, Nikolai N. Khodarev, Linda Janisch, Paul Chang, Jyoti D. Patel, Gini F. Fleming, John Moroney, Manish R. Sharma, Mark J. Ratain, Thomas F. Gajewski, Ralph R. Weichselbaum, and Steven J. Chmura, The University of Chicago, Chicago, IL; Julia R. White, The Ohio State University, Columbus, OH., Patel JD; Jason J. Luke, Jeffrey M. Lemons, Theodore G. Karrison, Sean P. Pitroda, James M. Melotek, Yuanyuan Zha, Hania A. Al-Hallaq, Ainhoa Arina, Nikolai N. Khodarev, Linda Janisch, Paul Chang, Jyoti D. Patel, Gini F. Fleming, John Moroney, Manish R. Sharma, Mark J. Ratain, Thomas F. Gajewski, Ralph R. Weichselbaum, and Steven J. Chmura, The University of Chicago, Chicago, IL; Julia R. White, The Ohio State University, Columbus, OH., Fleming GF; Jason J. Luke, Jeffrey M. Lemons, Theodore G. Karrison, Sean P. Pitroda, James M. Melotek, Yuanyuan Zha, Hania A. Al-Hallaq, Ainhoa Arina, Nikolai N. Khodarev, Linda Janisch, Paul Chang, Jyoti D. Patel, Gini F. Fleming, John Moroney, Manish R. Sharma, Mark J. Ratain, Thomas F. Gajewski, Ralph R. Weichselbaum, and Steven J. Chmura, The University of Chicago, Chicago, IL; Julia R. White, The Ohio State University, Columbus, OH., Moroney J; Jason J. Luke, Jeffrey M. Lemons, Theodore G. Karrison, Sean P. Pitroda, James M. Melotek, Yuanyuan Zha, Hania A. Al-Hallaq, Ainhoa Arina, Nikolai N. Khodarev, Linda Janisch, Paul Chang, Jyoti D. Patel, Gini F. Fleming, John Moroney, Manish R. Sharma, Mark J. Ratain, Thomas F. Gajewski, Ralph R. Weichselbaum, and Steven J. Chmura, The University of Chicago, Chicago, IL; Julia R. White, The Ohio State University, Columbus, OH., Sharma MR; Jason J. Luke, Jeffrey M. Lemons, Theodore G. Karrison, Sean P. Pitroda, James M. Melotek, Yuanyuan Zha, Hania A. Al-Hallaq, Ainhoa Arina, Nikolai N. Khodarev, Linda Janisch, Paul Chang, Jyoti D. Patel, Gini F. Fleming, John Moroney, Manish R. Sharma, Mark J. Ratain, Thomas F. Gajewski, Ralph R. Weichselbaum, and Steven J. Chmura, The University of Chicago, Chicago, IL; Julia R. White, The Ohio State University, Columbus, OH., White JR; Jason J. Luke, Jeffrey M. Lemons, Theodore G. Karrison, Sean P. Pitroda, James M. Melotek, Yuanyuan Zha, Hania A. Al-Hallaq, Ainhoa Arina, Nikolai N. Khodarev, Linda Janisch, Paul Chang, Jyoti D. Patel, Gini F. Fleming, John Moroney, Manish R. Sharma, Mark J. Ratain, Thomas F. Gajewski, Ralph R. Weichselbaum, and Steven J. Chmura, The University of Chicago, Chicago, IL; Julia R. White, The Ohio State University, Columbus, OH., Ratain MJ; Jason J. Luke, Jeffrey M. Lemons, Theodore G. Karrison, Sean P. Pitroda, James M. Melotek, Yuanyuan Zha, Hania A. Al-Hallaq, Ainhoa Arina, Nikolai N. Khodarev, Linda Janisch, Paul Chang, Jyoti D. Patel, Gini F. Fleming, John Moroney, Manish R. Sharma, Mark J. Ratain, Thomas F. Gajewski, Ralph R. Weichselbaum, and Steven J. Chmura, The University of Chicago, Chicago, IL; Julia R. White, The Ohio State University, Columbus, OH., Gajewski TF; Jason J. Luke, Jeffrey M. Lemons, Theodore G. Karrison, Sean P. Pitroda, James M. Melotek, Yuanyuan Zha, Hania A. Al-Hallaq, Ainhoa Arina, Nikolai N. Khodarev, Linda Janisch, Paul Chang, Jyoti D. Patel, Gini F. Fleming, John Moroney, Manish R. Sharma, Mark J. Ratain, Thomas F. Gajewski, Ralph R. Weichselbaum, and Steven J. Chmura, The University of Chicago, Chicago, IL; Julia R. White, The Ohio State University, Columbus, OH., Weichselbaum RR; Jason J. Luke, Jeffrey M. Lemons, Theodore G. Karrison, Sean P. Pitroda, James M. Melotek, Yuanyuan Zha, Hania A. Al-Hallaq, Ainhoa Arina, Nikolai N. Khodarev, Linda Janisch, Paul Chang, Jyoti D. Patel, Gini F. Fleming, John Moroney, Manish R. Sharma, Mark J. Ratain, Thomas F. Gajewski, Ralph R. Weichselbaum, and Steven J. Chmura, The University of Chicago, Chicago, IL; Julia R. White, The Ohio State University, Columbus, OH., Chmura SJ; Jason J. Luke, Jeffrey M. Lemons, Theodore G. Karrison, Sean P. Pitroda, James M. Melotek, Yuanyuan Zha, Hania A. Al-Hallaq, Ainhoa Arina, Nikolai N. Khodarev, Linda Janisch, Paul Chang, Jyoti D. Patel, Gini F. Fleming, John Moroney, Manish R. Sharma, Mark J. Ratain, Thomas F. Gajewski, Ralph R. Weichselbaum, and Steven J. Chmura, The University of Chicago, Chicago, IL; Julia R. White, The Ohio State University, Columbus, OH. |
| المصدر: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2018 Jun 01; Vol. 36 (16), pp. 1611-1618. Date of Electronic Publication: 2018 Feb 13. |
| نوع المنشور: | Clinical Trial, Phase I; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society of Clinical Oncology Country of Publication: United States NLM ID: 8309333 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1527-7755 (Electronic) Linking ISSN: 0732183X NLM ISO Abbreviation: J Clin Oncol |
| أسماء مطبوعة: | Publication: 2003- : Alexandria, VA : American Society of Clinical Oncology Original Publication: New York, N.Y. : Grune & Stratton, c1983- |
| مواضيع طبية MeSH: | Antibodies, Monoclonal, Humanized/*therapeutic use , Neoplasms/*drug therapy , Neoplasms/*radiotherapy , Radiosurgery/*methods, Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Humanized/adverse effects ; Antineoplastic Agents, Immunological/therapeutic use ; Biopsy ; Combined Modality Therapy ; Dose-Response Relationship, Radiation ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Radiosurgery/adverse effects ; Radiotherapy Dosage ; Response Evaluation Criteria in Solid Tumors ; Treatment Outcome |
| مستخلص: | Purpose Stereotactic body radiotherapy (SBRT) may stimulate innate and adaptive immunity to augment immunotherapy response. Multisite SBRT is an emerging paradigm for treating metastatic disease. Anti-PD-1-treatment outcomes may be improved with lower disease burden. In this context, we conducted a phase I study to evaluate the safety of pembrolizumab with multisite SBRT in patients with metastatic solid tumors. Patients and Methods Patients progressing on standard treatment received SBRT to two to four metastases. Not all metastases were targeted, and metastases > 65 mL were partially irradiated. SBRT dosing varied by site and ranged from 30 to 50 Gy in three to five fractions with predefined dose de-escalation if excess dose-limiting toxicities were observed. Pembrolizumab was initiated within 7 days after completion of SBRT. Pre- and post-SBRT biopsy specimens were analyzed in a subset of patients to quantify interferon-γ-induced gene expression. Results A total of 79 patients were enrolled; three patients did not receive any treatment and three patients only received SBRT. Patients included in the analysis were treated with SBRT and at least one cycle of pembrolizumab. Most (94.5%) of patients received SBRT to two metastases. Median follow-up for toxicity was 5.5 months (interquartile range, 3.3 to 8.1 months). Six patients experienced dose-limiting toxicities with no radiation dose reductions. In the 68 patients with imaging follow-up, the overall objective response rate was 13.2%. Median overall survival was 9.6 months (95% CI, 6.5 months to undetermined) and median progression-free survival was 3.1 months (95% CI, 2.9 to 3.4 months). Expression of interferon-γ-associated genes from post-SBRT tumor biopsy specimens significantly correlated with nonirradiated tumor response. Conclusion Multisite SBRT followed by pembrolizumab was well tolerated with acceptable toxicity. Additional studies exploring the clinical benefit and predictive biomarkers of combined multisite SBRT and PD-1-directed immunotherapy are warranted. |
| التعليقات: | Comment in: J Clin Oncol. 2018 Sep 1;36(25):2661-2662. (PMID: 29870291) Comment in: J Clin Oncol. 2018 Sep 1;36(25):2662-2663. (PMID: 29870292) |
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| معلومات مُعتمدة: | K12 CA139160 United States CA NCI NIH HHS; P30 CA014599 United States CA NCI NIH HHS; UL1 RR024999 United States RR NCRR NIH HHS |
| المشرفين على المادة: | 0 (Antibodies, Monoclonal, Humanized) 0 (Antineoplastic Agents, Immunological) DPT0O3T46P (pembrolizumab) |
| تواريخ الأحداث: | Date Created: 20180214 Date Completed: 20190726 Latest Revision: 20220321 |
| رمز التحديث: | 20240829 |
| مُعرف محوري في PubMed: | PMC5978468 |
| DOI: | 10.1200/JCO.2017.76.2229 |
| PMID: | 29437535 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1527-7755 |
|---|---|
| DOI: | 10.1200/JCO.2017.76.2229 |