Palbociclib in Patients With Non-Small-Cell Lung Cancer With CDKN2A Alterations: Results From the Targeted Agent and Profiling Utilization Registry Study

被引：65

作者：

Ahn, Eugene R. ^{[1
]}

Mangat, Pam K. ^{[2
]}

Garrett-Mayer, Elizabeth ^{[2
]}

Halabi, Susan ^{[3
]}

Dib, Elie G. ^{[4
]}

Haggstrom, Daniel E. ^{[5
]}

Alguire, Kathryn B. ^{[6
]}

Calfa, Carmen J. ^{[7
]}

Cannon, Timothy L. ^{[8
]}

Crilley, Pamela A. ^{[9
]}

Gaba, Anu G. ^{[10
]}

Marr, Alissa S. ^{[11
]}

Sangal, Ashish ^{[12
]}

Thota, Ramya ^{[13
]}

Antonelli, Kaitlyn R. ^{[2
]}

Islam, Samiha ^{[2
]}

Rygiel, Andrew L. ^{[2
]}

Bruinooge, Suanna S. ^{[2
]}

Schilsky, Richard L. ^{[2
]}

机构：

[1] Canc Treatment Ctr Amer, Chicago, IL USA

[2] Amer Soc Clin Oncol, 2318 Mill Rd, Alexandria, VA 22314 USA

[3] Duke Univ, Med Ctr, Durham, NC USA

[4] Michigan Canc Res Consortium, Ypsilanti, MI USA

[5] Levine Canc Inst, Charlotte, NC USA

[6] Canc Res Consortium West Michigan, Grand Rapids, MI USA

[7] Sylvester Comprehens Canc Ctr, Plantation, FL USA

[8] Inova Schar Canc Inst, Fairfax, VA USA

[9] Canc Treatment Ctr Amer, Philadelphia, PA USA

[10] Sanford Hlth, Sioux Falls, SD USA

[11] Univ Nebraska Med Ctr, Omaha, NE USA

[12] Canc Treatment Ctr Amer, Phoenix, AZ USA

[13] Intermt Healthcare, Salt Lake City, UT USA

来源：

JCO PRECISION ONCOLOGY | 2020年 / 4卷

关键词：

GENETIC ALTERATIONS;

D O I：

10.1200/PO.20.00037

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSEThe Targeted Agent and Profiling Utilization Registry (TAPUR) Study is a phase II pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancer with genomic alterations known to be drug targets. Results in a cohort of patients with non-small-cell lung cancer (NSCLC) with CDKN2A alterations treated with palbociclib are reported.METHODSEligible patients were >= 18 years old with advanced NSCLC, no remaining standard treatment options, measurable disease, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function. Patients with NSCLC with CDKN2A alterations and no Rb mutations received palbociclib 125 mg orally once daily for 21 days, followed by 7 days off. Simon's two-stage design was used with a primary study end point of objective response or stable disease (SD) of at least 16 weeks in duration. Secondary end points are progression-free survival (PFS), overall survival (OS), and safety.RESULTSTwenty-nine patients were enrolled from January 2017 to June 2018; two patients were not evaluable for response but were included in safety analyses. One patient with partial response and six patients with SD were observed, for a disease control rate of 31% (90% CI, 19% to 40%). Median PFS was 8.1 weeks (95% CI, 7.1 to 16.0 weeks), and median OS was 21.6 weeks (95% CI, 14.1 to 41.1 weeks). Eleven patients had at least 1 grade 3 or 4 adverse event (AE) or serious AE (SAE) possibly related to palbociclib (most common, cytopenias). Other AEs or SAEs possibly related to the treatment included anorexia, fatigue, febrile neutropenia, hypophosphatemia, sepsis, and vomiting.CONCLUSIONPalbociclib monotherapy demonstrated evidence of modest antitumor activity in heavily pretreated patients with NSCLC with CDKN2A alterations. Additional investigation is necessary to confirm efficacy and utility of palbociclib in this population.

引用

页码：757 / 766

页数：10

共 17 条

[1]

Al Baghdadi T., 2019, JCO Precis Oncol

[2] Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers [J].

Blakely, Collin M. ;

Watkins, Thomas B. K. ;

Wu, Wei ;

Gini, Beatrice ;

Chabon, Jacob J. ;

McCoach, Caroline E. ;

McGranahan, Nicholas ;

Wilson, Gareth A. ;

Birkbak, Nicolai J. ;

Olivas, Victor R. ;

Rotow, Julia ;

Maynard, Ashley ;

Wang, Victoria ;

Gubens, Matthew A. ;

Banks, Kimberly C. ;

Lanman, Richard B. ;

Caulin, Aleah F. ;

St John, John ;

Cordero, Anibal R. ;

Giannikopoulos, Petros ;

Simmons, Andrew D. ;

Mack, Philip C. ;

Gandara, David R. ;

Husain, Hatim ;

Doebele, Robert C. ;

Riess, Jonathan W. ;

Diehn, Maximilian ;

Swanton, Charles ;

Bivona, Trever G. .

NATURE GENETICS, 2017, 49 (12) :1693-+

[3]

Bruinooge SS, JCO PRECIS ONCOL

[4] Concomitant Genetic Alterations are Associated with Worse Clinical Outcome in EGFR Mutant NSCLC Patients Treated with Tyrosine Kinase Inhibitors [J].

Chang, Shih-Chieh ;

Lai, Yi-Chun ;

Chang, Cheng-Yu ;

Huang, Li-Kuo ;

Chen, Shu-Jen ;

Tan, Kien Thiam ;

Yu, Pei-Ning ;

Lai, Jiun-I .

TRANSLATIONAL ONCOLOGY, 2019, 12 (11) :1425-1431

[5] Palbociclib (PD0332991)-a Selective and Potent Cyclin-Dependent Kinase Inhibitor A Review of Pharmacodynamics and Clinical Development [J].

Clark, Amy S. ;

Karasic, Thomas B. ;

DeMichele, Angela ;

Vaughn, David J. ;

O'Hara, Mark ;

Perini, Rodolfo ;

Zhang, Paul ;

Lal, Priti ;

Feldman, Michael ;

Gallagher, Maryann ;

O'Dwyer, Peter J. .

JAMA ONCOLOGY, 2016, 2 (02) :253-260

[6] CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation [J].

Deng, Jiehui ;

Wang, Eric S. ;

Jenkins, Russell W. ;

Li, Shuai ;

Dries, Ruben ;

Yates, Kathleen ;

Chhabra, Sandeep ;

Huang, Wei ;

Liu, Hongye ;

Aref, Amir R. ;

Ivanova, Elena ;

Paweletz, Cloud P. ;

Bowden, Michaela ;

Zhou, Chensheng W. ;

Herter-Sprie, Grit S. ;

Sorrentino, Jessica A. ;

Bisi, John E. ;

Lizotte, Patrick H. ;

Merlino, Ashley A. ;

Quinn, Max M. ;

Bufe, Lauren E. ;

Yang, Annan ;

Zhang, Yanxi ;

Zhang, Hua ;

Gao, Peng ;

Chen, Ting ;

Cavanaugh, Megan E. ;

Rode, Amanda J. ;

Haines, Eric ;

Roberts, Patrick J. ;

Strum, Jay C. ;

Richards, William G. ;

Lorch, Jochen H. ;

Parangi, Sareh ;

Gunda, Viswanath ;

Boland, Genevieve M. ;

Bueno, Raphael ;

Palakurthi, Sangeetha ;

Freeman, Gordon J. ;

Ritz, Jerome ;

Haining, W. Nicholas ;

Sharpless, Norman E. ;

Arthanari, Haribabu ;

Shapiro, Geoffrey I. ;

Barbie, David A. ;

Gray, Nathanael S. ;

Wong, Kwok-Kin .

CANCER DISCOVERY, 2018, 8 (02) :216-233

[7] SWOG S1400C (NCT02154490)-A Phase II Study of Palbociclib for Previously Treated Cell Cycle Gene Alteration-Positive Patients with Stage IV Squamous Cell Lung Cancer (Lung-MAP Substudy) [J].

Edelman, Martin J. ;

Redman, Mary W. ;

Albain, Kathy S. ;

McGary, Eric C. ;

Rafique, Noman M. ;

Petro, Daniel ;

Waqar, Saiama N. ;

Minichiello, Katherine ;

Miao, Jieling ;

Papadimitrakopoulou, Vassiliki A. ;

Kelly, Karen ;

Gandara, David R. ;

Herbst, Roy S. .

JOURNAL OF THORACIC ONCOLOGY, 2019, 14 (10) :1853-1859

[8] A randomized phase 3 study of abemaciclib versus erlotinib in previously treated patients with stage IV NSCLC with KRAS mutation: JUNIPER. [J].

Goldman, Jonathan Wade ;

Mazieres, Julien ;

Barlesi, Fabrice ;

Koczywas, Marianna ;

Dragnev, Konstantin H. ;

Goksel, Tuncay ;

Cortot, Alexis B. ;

Girard, Nicolas ;

Wesseler, Claas ;

Bischoff, Helge ;

Nadal, Ernest ;

Park, Keunchil ;

Lu, Shun ;

Taus, Alvaro ;

Cobo, Manuel ;

Hurt, Karla ;

Chiang, Alan ;

Hossain, Anwar ;

John, William J. ;

Paz-Ares, Luis G. .

JOURNAL OF CLINICAL ONCOLOGY, 2018, 36 (15)

[9] Clinical activity of LY2835219, a novel cell cycle inhibitor selective for CDK4 and CDK6, in patients with non-small cell lung cancer. [J].

Goldman, Jonathan Wade ;

Gandhi, Leena ;

Patnaik, Amita ;

Rosen, Lee S. ;

Hilton, John Frederick ;

Papadopoulos, Kyriakos P. ;

Tolaney, Sara M. ;

Beeram, Muralidhar ;

Rasco, Drew Warren ;

Myrand, Scott P. ;

Beckmann, Richard P. ;

Kulanthaivel, Palaniappan ;

Frenzel, Martin ;

Cronier, Damien ;

Chan, Edward M. ;

Flaherty, Keith ;

Wen, Patrick Y. ;

Tolcher, Anthony W. ;

Shapiro, Geoffrey .

JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (15)

[10]

Gopalan Priya K, 2018, Oncotarget, V9, P37352, DOI 10.18632/oncotarget.26424

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