Douglas Adkins1, Jessica Ley2, Omar Atiq3, Steven Powell4, William C Spanos4, Mark Gitau5, Caron Rigden6, Kevin Palka6, Jingxia Liu7, Peter Oppelt6. 1. Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, United States; Division of Medical Oncology, Washington University School of Medicine, St. Louis, MO, United States. Electronic address: dadkins@wustl.edu. 2. Division of Medical Oncology, Washington University School of Medicine, St. Louis, MO, United States. 3. Winthrop P. Rockefeller Cancer Institute, University of Arkansas Medical System, Little Rock, AR, United States. 4. Sanford Cancer Center, Sanford Health, Sioux Falls, SD, United States. 5. Sanford Cancer Center, Sanford Health, Fargo, ND, United States. 6. Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, United States; Division of Medical Oncology, Washington University School of Medicine, St. Louis, MO, United States. 7. Biostatistics Shared Resource, Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, United States.
Abstract
OBJECTIVES: Macropinocytosis promotes internalization of albumin into cells to serve as a nutrient supply and is constitutively driven by signaling pathways frequently hyperactivated in head and neck squamous-cell carcinoma (HNSCC). In this way, drugs bound to albumin may selectively target HNSCC. nab-paclitaxel is a nanoparticle albumin-bound formulation of paclitaxel that improves drug delivery into tumor compared to paclitaxel. The primary aim of this single-arm, multicenter, phase 2 trial was to determine if nab-paclitaxel, cetuximab, and carboplatin (CACTUX regimen) would result in longer progression-free survival (PFS) than the historical regimen (EXTREME: 5-fluorouracil, cetuximab, and a platinum). MATERIALS AND METHODS: Patients with untreated recurrent or metastatic HNSCC received six, three-week cycles of nab-paclitaxel, cetuximab, and carboplatin, followed by maintenance nab-paclitaxel and cetuximab until progression. We hypothesized the median PFS with CACTUX would be 35% longer than with EXTREME (corresponding to 7.6 vs 5.6 months; power 0.80, α = 0.05, one-sided test, n = 70). Secondary outcomes included objective response rate (ORR) and overall survival (OS). RESULTS: Seventy-four patients enrolled into the trial; seventy were evaluable. The median PFS was 6.1 months (95% CI, 4.1-7.4). The ORR was 60%. Median follow-up was 18 months (IQR: 4.7-23). The median OS was 17.8 months (95% CI, 8.5-21.7) for all patients, and 19.8 months (95% CI, 10.9-22.0) for human papillomavirus (HPV)-related oropharynx SCC and 14.0 months (95% CI, 4.6-23.3) for HPV-unrelated HNSCC. CONCLUSION: Among patients with recurrent or metastatic HNSCC, CACTUX did not result in a longer PFS than historical EXTREME. However, CACTUX did result in a more favorable ORR and OS.
OBJECTIVES: Macropinocytosis promotes internalization of albumin into cells to serve as a nutrient supply and is constitutively driven by signaling pathways frequently hyperactivated in head and neck squamous-cell carcinoma (HNSCC). In this way, drugs bound to albumin may selectively target HNSCC. nab-paclitaxel is a nanoparticle albumin-bound formulation of paclitaxel that improves drug delivery into tumor compared to paclitaxel. The primary aim of this single-arm, multicenter, phase 2 trial was to determine if nab-paclitaxel, cetuximab, and carboplatin (CACTUX regimen) would result in longer progression-free survival (PFS) than the historical regimen (EXTREME: 5-fluorouracil, cetuximab, and a platinum). MATERIALS AND METHODS: Patients with untreated recurrent or metastatic HNSCC received six, three-week cycles of nab-paclitaxel, cetuximab, and carboplatin, followed by maintenance nab-paclitaxel and cetuximab until progression. We hypothesized the median PFS with CACTUX would be 35% longer than with EXTREME (corresponding to 7.6 vs 5.6 months; power 0.80, α = 0.05, one-sided test, n = 70). Secondary outcomes included objective response rate (ORR) and overall survival (OS). RESULTS: Seventy-four patients enrolled into the trial; seventy were evaluable. The median PFS was 6.1 months (95% CI, 4.1-7.4). The ORR was 60%. Median follow-up was 18 months (IQR: 4.7-23). The median OS was 17.8 months (95% CI, 8.5-21.7) for all patients, and 19.8 months (95% CI, 10.9-22.0) for human papillomavirus (HPV)-related oropharynx SCC and 14.0 months (95% CI, 4.6-23.3) for HPV-unrelated HNSCC. CONCLUSION: Among patients with recurrent or metastatic HNSCC, CACTUX did not result in a longer PFS than historical EXTREME. However, CACTUX did result in a more favorable ORR and OS.
Authors: Michael K Gibson; Yi Li; Barbara Murphy; Maha H A Hussain; Ronald C DeConti; John Ensley; Arlene A Forastiere Journal: J Clin Oncol Date: 2005-05-20 Impact factor: 44.544
Authors: P Bossi; R Miceli; L D Locati; D Ferrari; S Vecchio; G Moretti; N Denaro; F Caponigro; M Airoldi; C Moro; E Vaccher; A Sponghini; A Caldara; G Rinaldi; F Ferrau; F Nolè; S Lo Vullo; F Tettamanzi; L Hollander; L Licitra Journal: Ann Oncol Date: 2017-11-01 Impact factor: 32.976
Authors: Wantong Yao; Johnathon L Rose; Wei Wang; Sahil Seth; Hong Jiang; Ayumu Taguchi; Jintan Liu; Liang Yan; Avnish Kapoor; Pingping Hou; Ziheng Chen; Qiuyun Wang; Luigi Nezi; Zhaohui Xu; Jun Yao; Baoli Hu; Piergiorgio F Pettazzoni; I Lin Ho; Ningping Feng; Vandhana Ramamoorthy; Shan Jiang; Pingna Deng; Grace J Ma; Peter Den; Zhi Tan; Shu Xing Zhang; Huamin Wang; Y Alan Wang; Angela K Deem; Jason B Fleming; Alessandro Carugo; Timothy P Heffernan; Anirban Maitra; Andrea Viale; Haoqiang Ying; Samir Hanash; Ronald A DePinho; Giulio F Draetta Journal: Nature Date: 2019-03-27 Impact factor: 49.962
Authors: Cosimo Commisso; Shawn M Davidson; Rengin G Soydaner-Azeloglu; Seth J Parker; Jurre J Kamphorst; Sean Hackett; Elda Grabocka; Michel Nofal; Jeffrey A Drebin; Craig B Thompson; Joshua D Rabinowitz; Christian M Metallo; Matthew G Vander Heiden; Dafna Bar-Sagi Journal: Nature Date: 2013-05-12 Impact factor: 49.962
Authors: Christina Fitzmaurice; Tomi F Akinyemiju; Faris Hasan Al Lami; Tahiya Alam; Reza Alizadeh-Navaei; Christine Allen; Ubai Alsharif; Nelson Alvis-Guzman; Erfan Amini; Benjamin O Anderson; Olatunde Aremu; Al Artaman; Solomon Weldegebreal Asgedom; Reza Assadi; Tesfay Mehari Atey; Leticia Avila-Burgos; Ashish Awasthi; Huda Omer Ba Saleem; Aleksandra Barac; James R Bennett; Isabela M Bensenor; Nickhill Bhakta; Hermann Brenner; Lucero Cahuana-Hurtado; Carlos A Castañeda-Orjuela; Ferrán Catalá-López; Jee-Young Jasmine Choi; Devasahayam Jesudas Christopher; Sheng-Chia Chung; Maria Paula Curado; Lalit Dandona; Rakhi Dandona; José das Neves; Subhojit Dey; Samath D Dharmaratne; David Teye Doku; Tim R Driscoll; Manisha Dubey; Hedyeh Ebrahimi; Dumessa Edessa; Ziad El-Khatib; Aman Yesuf Endries; Florian Fischer; Lisa M Force; Kyle J Foreman; Solomon Weldemariam Gebrehiwot; Sameer Vali Gopalani; Giuseppe Grosso; Rahul Gupta; Bishal Gyawali; Randah Ribhi Hamadeh; Samer Hamidi; James Harvey; Hamid Yimam Hassen; Roderick J Hay; Simon I Hay; Behzad Heibati; Molla Kahssay Hiluf; Nobuyuki Horita; H Dean Hosgood; Olayinka S Ilesanmi; Kaire Innos; Farhad Islami; Mihajlo B Jakovljevic; Sarah Charlotte Johnson; Jost B Jonas; Amir Kasaeian; Tesfaye Dessale Kassa; Yousef Saleh Khader; Ejaz Ahmad Khan; Gulfaraz Khan; Young-Ho Khang; Mohammad Hossein Khosravi; Jagdish Khubchandani; Jacek A Kopec; G Anil Kumar; Michael Kutz; Deepesh Pravinkumar Lad; Alessandra Lafranconi; Qing Lan; Yirga Legesse; James Leigh; Shai Linn; Raimundas Lunevicius; Azeem Majeed; Reza Malekzadeh; Deborah Carvalho Malta; Lorenzo G Mantovani; Brian J McMahon; Toni Meier; Yohannes Adama Melaku; Mulugeta Melku; Peter Memiah; Walter Mendoza; Tuomo J Meretoja; Haftay Berhane Mezgebe; Ted R Miller; Shafiu Mohammed; Ali H Mokdad; Mahmood Moosazadeh; Paula Moraga; Seyyed Meysam Mousavi; Vinay Nangia; Cuong Tat Nguyen; Vuong Minh Nong; Felix Akpojene Ogbo; Andrew Toyin Olagunju; Mahesh Pa; Eun-Kee Park; Tejas Patel; David M Pereira; Farhad Pishgar; Maarten J Postma; Farshad Pourmalek; Mostafa Qorbani; Anwar Rafay; Salman Rawaf; David Laith Rawaf; Gholamreza Roshandel; Saeid Safiri; Hamideh Salimzadeh; Juan Ramon Sanabria; Milena M Santric Milicevic; Benn Sartorius; Maheswar Satpathy; Sadaf G Sepanlou; Katya Anne Shackelford; Masood Ali Shaikh; Mahdi Sharif-Alhoseini; Jun She; Min-Jeong Shin; Ivy Shiue; Mark G Shrime; Abiy Hiruye Sinke; Mekonnen Sisay; Amber Sligar; Muawiyyah Babale Sufiyan; Bryan L Sykes; Rafael Tabarés-Seisdedos; Gizachew Assefa Tessema; Roman Topor-Madry; Tung Thanh Tran; Bach Xuan Tran; Kingsley Nnanna Ukwaja; Vasiliy Victorovich Vlassov; Stein Emil Vollset; Elisabete Weiderpass; Hywel C Williams; Nigus Bililign Yimer; Naohiro Yonemoto; Mustafa Z Younis; Christopher J L Murray; Mohsen Naghavi Journal: JAMA Oncol Date: 2018-11-01 Impact factor: 31.777