Article
Oncology
Paolo A. Ascierto, Brigitte Dreno, James Larkin, Antoni Ribas, Gabriella Liszkay, Michele Maio, Mario Mandala, Lev Demidov, Daniil Stroyakovskiy, Luc Thomas, Luis de la Cruz-Merino, Victoria Atkinson, Caroline Dutriaux, Claus Garbe, Jessie Hsu, Surai Jones, Haocheng Li, Edward McKenna, Athina Voulgari, Grant A. McArthur
Summary: The long-term follow-up of the coBRIM study confirmed the extended clinical benefit and safety profile of cobimetinib plus vemurafenib compared to vemurafenib monotherapy in patients with BRAF(V600) mutation-positive advanced melanoma. The study showed improved progression-free survival and overall survival in the cobimetinib plus vemurafenib group, with the safety profile remaining consistent with previous reports.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Katharina C. Kaehler, Ralf Gutzmer, Friedegrund Meier, Lisa Zimmer, Markus Heppt, Anja Gesierich, Kai-Martin Thoms, Jochen Utikal, Jessica C. Hassel, Carmen Loquai, Claudia Pfoehler, Lucie Heinzerling, Martin Kaatz, Daniela Goeppner, Annette Pflugfelder, Ann-Sophie Bohne, Imke Satzger, Lydia Reinhardt, Jan-Malte Placke, Dirk Schadendorf, Selma Ugurel
Summary: The development of an early exanthema within 6 weeks after treatment start indicates a favorable therapy outcome upon vemurafenib plus cobimetinib. Patients presenting with an early exanthema should therefore be treated with adequate supportive measures to provide that patients can stay on treatment. In the COBIVEM cohort, patients with a mild early exanthema had a superior survival outcome compared to patients with a severe or non early exanthema.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Yufan Tan, Xiaoyu Zhong, Xizhi Wen, Leyi Yao, Zhenlong Shao, Wenshuang Sun, Jiawen Wu, Guanmei Wen, Daolin Tang, Xiaoshi Zhang, Yuning Liao, Jinbao Liu
Summary: A study showed that blood bilirubin levels in BRAF-mutant melanoma patients treated with vemurafenib are inversely correlated with clinical outcomes. Bilirubin can counteract the growth-inhibiting and apoptosis-inducing effects of vemurafenib on melanoma cells by activating the ERK-MNK1 axis. This highlights the negative impact of bilirubin on the effectiveness of vemurafenib in treating BRAF-mutant melanoma.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Ma del Carmen Alamo, Sebastian Ochenduszko, Guillermo Crespo, Monica Corral, Juana Oramas, Pilar Sancho, Javier Medina, Fernando Garicano, Pedro Lopez, Begona Campos Balea, Analia Rodriguez Garzotto, Eva Munoz-Couselo
Summary: The study evaluated the efficacy of combination therapy with vemurafenib/cobimetinib in terms of durability, finding that one-third of patients achieved a sustained complete response. Factors such as body mass index may influence the durability of the response in patients with advanced melanoma.
ONCOTARGETS AND THERAPY
(2021)
Article
Oncology
Kristina V. Orlova, Evgeniy V. Ledin, Natalia V. Zhukova, Rashida V. Orlova, Elena V. Karabina, Mikhail V. Volkonskiy, Daniil L. Stroyakovskiy, Aleksandr N. Yurchenkov, Svetlana A. Protsenko, Alexey V. Novik, Ludmila V. Vorotilina, Fedor V. Moiseenko, Victor L. Chang, Aleksandr I. Kazmin, Svetlana A. Tkachenko, Sergey V. Gamaunov, David R. Naskhletashvili, Igor V. Samoylenko, Anastasia S. Vikhrova, Igor A. Utyashev, Galina Yu. Kharkevich, Natalia N. Petenko, Irina Zh. Shubina, Lev V. Demidov
Summary: Real-world data on treatment patterns and clinical outcomes for advanced BRAF V600 mutant melanoma patients are limited, but the study shows the effectiveness and good safety profile of combined TT with BRAF plus MEK inhibitors across all lines of therapy, including patients with brain metastases.
Article
Oncology
C. Robert, K. D. Lewis, R. Gutzmer, D. Stroyakovskiy, H. Gogas, S. Protsenko, R. P. Pereira, T. Eigentler, P. Rutkowski, L. Demidov, I Caro, H. Forbes, K. Shah, Y. Yan, H. Li, G. A. McArthur, P. A. Ascierto
Summary: The triplet combination therapy of atezolizumab, vemurafenib, and cobimetinib demonstrated improved progression-free survival in patients with BRAF-mutated advanced melanoma. Exploratory biomarker analyses identified potential predictors including tumor mutational burden, interferon-gamma expression, and PD-L1 expression.
ANNALS OF ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anne Uebel, Stefanie Kewitz-Hempel, Edith Willscher, Kathleen Gebhardt, Cord Sunderkoetter, Dennis Gerloff
Summary: Activating BRAF mutations are present in 50-60% of malignant melanomas. Inhibiting EZH2 or its downstream target PLK1, in combination with BRAF inhibitors, may provide potential novel therapeutic options for melanomas with BRAF mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Livio Pagano, Marianna Criscuolo, Alessandro Broccoli, Alfonso Piciocchi, Marzia Varettoni, Eugenio Galli, Antonella Anastasia, Maria Cantonetti, Livio Trentin, Sofia Kovalchuk, Lorella Orsucci, Annamaria Frustaci, Angelica Spolzino, Stefano Volpetti, Ombretta Annibali, Sergio Storti, Caterina Stelitano, Francesco Marchesi, Massimo Offidani, Beatrice Casadei, Maria Elena Nizzoli, Maria Lucia De Luca, Luana Fianchi, Marina Motta, Luca Guarnera, Edoardo Simonetti, Andrea Visentin, Francesco Vassallo, Marina Deodato, Chiara Sarlo, Attilio Olivieri, Brunangelo Falini, Alessandro Pulsoni, Enrico Tiacci, Pier Luigi Zinzani
Summary: The first-line treatment with cladribine (2CDA) for hairy cell leukemia (HCL) has shown excellent efficacy, safety, and long-term remission rates. The overall survival (OS) of HCL patients treated with 2CDA is high, with a significant difference in duration of response between complete remission (CR) and partial remission (PR) patients.
BLOOD CANCER JOURNAL
(2022)
Article
Oncology
Filippo de Braud, Christophe Dooms, Rebecca S. Heist, Celeste Lebbe, Martin Wermke, Anas Gazzah, Dirk Schadendorf, Piotr Rutkowski, Juergen Wolf, Paolo A. Ascierto, Ignacio Gil-Bazo, Shumei Kato, Maria Wolodarski, Meredith McKean, Eva Munoz Couselo, Martin Sebastian, Armando Santoro, Vesselina Cooke, Luca Manganelli, Kitty Wan, Anil Gaur, Jaeyeon Kim, Giordano Caponigro, Xuan-Mai Couillebault, Helen Evans, Catarina D. Campbell, Sumit Basu, Michele Moschetta, Adil Daud
Summary: This study explores a targeted therapy for treating NRAS-mutant melanoma, showing promising antitumor activity in patients with the use of LXH254 and trametinib in combination.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Andreas M. Schmitt, Lucy Dumas, James Larkin
Summary: The combination of atezolizumab, cobimetinib, and vemurafenib demonstrates superior progression-free survival in patients with metastatic melanoma compared to cobimetinib and vemurafenib alone. Triplet therapy may be considered in urgent situations for disease control, when BRAF/MEK inhibition is chosen as the first-line treatment over immune checkpoint inhibition. However, further follow-up and comparison with ipilimumab and nivolumab combination are needed to determine the future role of this combination.
EXPERT REVIEW OF ANTICANCER THERAPY
(2022)
Article
Oncology
Manali S. Phadke, Zhihua Chen, Jiannong Li, Eslam Mohamed, Michael A. Davies, Inna Smalley, Derek R. Duckett, Vinayak Palve, Brian J. Czerniecki, Peter A. Forsyth, David Noyes, Dennis O. Adeegbe, Zeynep Eroglu, Kimberly T. Nguyen, Kenneth Y. Tsai, Uwe Rix, Christin E. Burd, Yian A. Chen, Paulo C. Rodriguez, Keiran S. M. Smalley
Summary: In mouse models of BRAF- and NRAS-mutant melanoma, upfront immunotherapy enhances responses to targeted therapy. The sequence of IT -> TT modulates the immune environment, increasing infiltration of T cells and decreasing tumor-associated macrophages, leading to improved therapeutic outcomes. Durable responses to the IT -> TT sequence depend on T-cell activity and enrichment of a population of melanoma cells with increased expression of MHC class I and melanoma antigens.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Medicine, General & Internal
Pawel Rogala, Anna M. Czarnecka, Bozena Cybulska-Stopa, Krzysztof Ostaszewski, Karolina Piejko, Marcin Zietek, Robert Dziura, Ewa Rutkowska, Lukasz Galus, Natasza Kempa-Kaminska, Jacek Calik, Agata Salek-Zan, Tomasz Zemelka, Wieslaw Bal, Agnieszka Kamycka, Tomasz Switaj, Grazyna Kaminska-Winciorek, Rafal Suwinski, Jacek Mackiewicz, Piotr Rutkowski
Summary: Limited data is available on the sequencing of targeted therapy and immunotherapy in patients with BRAF-mutant melanoma. This study demonstrates the effectiveness of BRAFi/MEKi therapy as a second-line treatment for advanced melanoma patients, with similar efficacy observed for all combinations of BRAFi/MEKi.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Nadine Kretschmer, Christin Durchschein, Antje Hufner, Beate Rinner, Birgit Lohberger, Rudolf Bauer
Summary: In this study, a novel shikonin derivative called SK119 was synthesized and evaluated for its pharmacological effects on human melanoma cells. SK119 exhibited promising activity in a nano-molar range and showed synergistic effects with vemurafenib and cobimetinib, two clinically used melanoma therapeutics. Further research indicates the potential of SK119 in melanoma therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Malcolm P. Huestis, Darlene Dela Cruz, Antonio G. DiPasquale, Matthew R. Durk, Charles Eigenbrot, Paul Gibbons, Alberto Gobbi, Thomas L. Hunsaker, Hank La, Dennis H. Leung, Wendy Liu, Shiva Malek, Mark Merchant, John G. Moffat, Christine S. Muli, Christine J. Orr, Brendan T. Parr, Frances Shanahan, Christopher J. Sneeringer, Weiru Wang, Ivana Yen, Jianping Yin, Michael Siu, Joachim Rudolph
Summary: GNE-0749 is a type II pan-RAF inhibitor with a fluoroquinazolinone hinge-binding motif, which enhances its kinase selectivity by minimizing reliance on common polar hinge contacts. Strategic substitution of fluorine at the C5 position increases solubility and enables oral dosing, leading to significant tumor growth inhibition in combination with the MEK inhibitor cobimetinib in a KRAS mutant xenograft mouse model.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Carlotta Guzzetti, Cristina Corno, Elisabetta Vergani, Luca Mirra, Emilio Ciusani, Monica Rodolfo, Paola Perego, Giovanni L. Beretta
Summary: KiSS1, a metastasis suppressor, plays an important role in the development and puberty of melanoma cells. This study found that kisspeptin 54, a cleavage product of KiSS1, can enhance the pro-apoptotic activity of vemurafenib in melanoma cells, including drug-resistant cells. These findings suggest the potential of using KiSS1 to modulate apoptotic response.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Omid Hamid, Rubina Ismail, Igor Puzanov
Article
Oncology
Janice M. Mehnert, Emily Bergsland, Bert H. O'Neil, Armando Santoro, Jan H. M. Schellens, Roger B. Cohen, Toshihiko Doi, Patrick A. Ott, Michael J. Pishvaian, Igor Puzanov, Kyaw L. Aung, Chiun Hsu, Christophe Le Tourneau, Antoine Hollebecque, Elena Elez, Kenji Tamura, Marlena Gould, Ping Yang, Karen Stein, Sarina A. Piha-Paul
Editorial Material
Medicine, Research & Experimental
Franco Maria Buonaguro, Igor Puzanov, Paolo Antonio Ascierto
JOURNAL OF TRANSLATIONAL MEDICINE
(2020)
Article
Medicine, Research & Experimental
Paolo A. Ascierto, Sanjiv S. Agarwala, Alexander Eggermont, Jeffrey E. Gershenwald, Jean-Jacques Grob, Omid Hamid, Olivier Michielin, Michael Postow, Igor Puzanov, Hassane M. Zarour, Corrado Caraco, Alessandro Testori
JOURNAL OF TRANSLATIONAL MEDICINE
(2020)
Review
Oncology
Rohit Gosain, Yara Abdou, Abhay Singh, Navpreet Rana, Igor Puzanov, Marc S. Ernstoff
CURRENT ONCOLOGY REPORTS
(2020)
Article
Multidisciplinary Sciences
Takayoshi Yamauchi, Toshifumi Hoki, Takaaki Oba, Vaibhav Jain, Hongbin Chen, Kristopher Attwood, Sebastiano Battaglia, Saby George, Gurkamal Chatta, Igor Puzanov, Carl Morrison, Kunle Odunsi, Brahm H. Segal, Grace K. Dy, Marc S. Ernstoff, Fumito Ito
Summary: Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment but durable response is limited. CX3CR1, a marker of T-cell differentiation, is investigated as a predictor of response to ICI therapy. Treatment with ICI increases the frequency of circulating CX3CR1(+)CD8(+) T cells and correlates with response and survival in patients with non-small cell lung cancer.
NATURE COMMUNICATIONS
(2021)
Review
Oncology
Benjamin Switzer, Igor Puzanov, Joseph J. Skitzki, Lamya Hamad, Marc S. Ernstoff
Summary: This review summarizes the historical and future advances regarding the translational and clinical implications of advanced melanoma and provides multidisciplinary recommendations to aid clinicians in the navigation of current treatment approaches for a variety of patient cohorts.
JCO ONCOLOGY PRACTICE
(2022)
Article
Oncology
Jason A. Chesney, Antoni Ribas, Georgina Long, John M. Kirkwood, Reinhard Dummer, Igor Puzanov, Christoph Hoeller, Thomas F. Gajewski, Ralf Gutzmer, Piotr Rutkowski, Lev Demidov, Petr Arenberger, Sang Joon Shin, Pier Francesco Ferrucci, Andrew Haydon, John Hyngstrom, Johannes van Thienen, Sebastian Haferkamp, Josep Malvehy Guilera, Bernardo Leon Rapoport, Ari VanderWalde, Scott J. Diede, James R. Anderson, Sheryl Treichel, Edward L. Chan, Sumita Bhatta, Jennifer Gansert, Frank Stephen Hodi, Helen Gogas
Summary: In this phase III study, the combination of T-VEC and pembrolizumab did not significantly improve progression-free survival or overall survival in patients with advanced melanoma. These findings indicate that this combination therapy is not effective in this patient population.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Jason A. Chesney, Igor Puzanov, Frances A. Collichio, Parminder Singh, Mohammed M. Milhem, John Glaspy, Omid Hamid, Merrick Ross, Philip Friedlander, Claus Garbe, Theodore Logan, Axel Hauschild, Celeste Lebbe, Harshada Joshi, Wendy Snyder, Janice M. Mehnert
Summary: In a randomized phase II study, the combination of T-VEC and ipilimumab showed greater antitumor activity compared to ipilimumab alone in patients with advanced melanoma. The 5-year outcomes demonstrated long-lasting efficacy and safety for the combination therapy of an oncolytic virus and a checkpoint inhibitor.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Islam Eljilany, Payman Ghasemi Saghand, James Chen, Aakrosh Ratan, Martin McCarter, John Carpten, Howard Colman, Alexandra P. Ikeguchi, Igor Puzanov, Susanne Arnold, Michelle Churchman, Patrick Hwu, Jose Conejo-Garcia, William S. Dalton, George J. Weiner, Issam M. El Naqa, Ahmad A. Tarhini
Summary: In this study, the prognostic value of immunoscore calculated from real-world transcriptomic data was evaluated in patients with advanced malignancies treated with immune checkpoint inhibitors. The results demonstrated that the immunoscore could predict patients at risk of death, with better overall survival observed in patients with intermediate-high immunoscore.
Article
Oncology
Lei Deng, Changchuan Jiang, Kristopher Attwood, Joseph J. Zhao, Stuthi Perimbeti, Chen Hu, Igor Puzanov, Grace K. Dy
Summary: Durable progression-free survivors (dPFSors) over 2 years have been reported among patients with melanoma or non-small-cell lung cancer (NSCLC) who received PD-(L)1 therapy. However, risk of progression still exists and the optimal imaging surveillance interval is unknown.
JCO ONCOLOGY PRACTICE
(2023)
Meeting Abstract
Oncology
Latha Shivakumar, Christine B. Weldon, Ali McBride, Igor Puzanov, Joanne Riemer, Matthew R. Zibelman, Leigh Boehmer
JOURNAL OF CLINICAL ONCOLOGY
(2020)
Meeting Abstract
Medicine, Research & Experimental
Adi Diab, Igor Puzanov, Michele Maio, Brendan Curti, Mehmet Bilen, Karl Lewis, Scott Tykodi, Gregory Daniels, Alexander Spira, Chantale Bernatchez, Salah Eddine Bentebibel, Michael Wong, James Larkin, Ewa Kalinka-Warzocha, Sunny Xie, Sue Currie, Ute Hoch, Wei Lin, Mary Tagliaferri, Stina Singel, Michael Hurwitz
JOURNAL OF TRANSLATIONAL MEDICINE
(2020)