Wee1 Inhibition in Recurrent Serous Uterine Cancer: Science Paving the Way in a Challenging Disease

Ainhoa Madariaga , MD1,2 and Amit M. Oza , MD1,2

doi : 10.1200/JCO.21.00288

Journal of Clinical Oncology 39, no. 14 (May 10, 2021) 1513-1517.

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Palbociclib for Residual High-Risk Invasive HR-Positive and HER2-Negative Early Breast Cancer—The Penelope-B Trial

Sibylle Loibl , MD, PhD1,2; Frederik Marmé , MD, PhD3; Miguel Martin , MD, PhD4,5; Michael Untch , MD, PhD6; Hervé Bonnefoi , MD, PhD7; Sung-Bae Kim , MD, PhD8; Harry Bear, MD, PhD9,10; Nicole McCarthy, MD, PhD11; Mireia Melé Olivé , MD5,12; Karen Gelmon, MD, PhD13; José Garc?a-S?enz, MD5,14; Catherine M. Kelly, MD15; Toralf Reimer , MD, PhD16; Masakazu Toi , MD, PhD17; Hope S. Rugo , MD18; Carsten Denkert , MD, PhD1,19; Michael Gnant, MD, PhD20,21; Andreas Makris, MD22; Maria Koehler, MD, PhD23; Cynthia Huang-Bartelett , MD23; Maria Jose Lechuga Frean, MD23; Marco Colleoni , MD24; Gustavo Werutsky , MD25; Sabine Seiler, MD1; Nicole Burchardi, PhD1; Valentina Nekljudova , PhD1; and Gunter von Minckwitz, MD, PhD, MA (Phil), BBA1

doi : 10.1200/JCO.20.03639

Journal of Clinical Oncology 39, no. 14 (May 10, 2021) 1518-1530.

About one third of patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative breast cancer who have residual invasive disease after neoadjuvant chemotherapy (NACT) will relapse. Thus, additional therapy is needed. Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor demonstrating efficacy in the metastatic setting.

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Phase II Study of the WEE1 Inhibitor Adavosertib in Recurrent Uterine Serous Carcinoma

Joyce F. Liu, MD, MPH1; Niya Xiong, MS2; Susana M. Campos, MD1; Alexi A. Wright, MD, MPH1; Carolyn Krasner, MD1; Susan Schumer, MD1; Neil Horowitz, MD3; Jennifer Veneris, MD, PhD1; Nabihah Tayob, PhD2; Stephanie Morrissey, RN, BSN1; Gabriela West, BA1; Roxanne Quinn, BA1; Ursula A. Matulonis, MD1; and Panagiotis A. Konstantinopoulos, MD, PhD1

doi : 10.1200/JCO.20.03167

Journal of Clinical Oncology 39, no. 14 (May 10, 2021) 1531-1539.

Uterine serous carcinoma (USC) is a distinct histologic subtype of endometrial cancer, with molecular characteristics suggesting frequent cell-cycle dysregulation paired with a high level of oncogene-driven replication stress. Adavosertib is a potent and selective oral inhibitor of the WEE1 kinase, a key regulator of the G2/M and S phase cell-cycle checkpoints. Because cells with impaired cell-cycle regulation and high replication stress may be vulnerable to WEE1 inhibition, we conducted this study to assess the activity of adavosertib monotherapy in women with recurrent USC.

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Favorable Trisomies and ETV6-RUNX1 Predict Cure in Low-Risk B-Cell Acute Lymphoblastic Leukemia: Results From Children's Oncology Group Trial AALL0331

Leonard A. Mattano Jr, MD1; Meenakshi Devidas, PhD2; Kelly W. Maloney, MD3; Cindy Wang, MS4; Alison M. Friedmann, MD5; Patrick Buckley, MD6; Michael J. Borowitz, MD7; Andrew J. Carroll, MD8; Julie M. Gastier-Foster, MD9,10; Nyla A. Heerema, PhD11; Nina S. Kadan-Lottick, MD12; Yousif H. Matloub, MD13; David T. Marshall, MD14; Linda C. Stork, MD15; Mignon L. Loh, MD16; Elizabeth A. Raetz, MD17; Brent L. Wood, MD18; Stephen P. Hunger, MD19; William L. Carroll, MD17; and Naomi J. Winick, MD20

doi : 10.1200/JCO.20.02370

Journal of Clinical Oncology 39, no. 14 (May 10, 2021) 1540-1552.

Children's Oncology Group (COG) AALL0331 tested whether pegaspargase intensification on a low-intensity chemotherapy backbone would improve the continuous complete remission (CCR) rate in a low-risk subset of children with standard-risk B-acute lymphoblastic leukemia (ALL).

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Survival and New Prognosticators in Metastatic Seminoma: Results From the IGCCCG-Update Consortium

J?rg Beyer , MD1; Laurence Collette , PhD2; Nicolas Sauvé , MSc2; Gedske Daugaard , MD3; Darren R. Feldman , MD4,5; Torgrim Tandstad, MD6; Alexey Tryakin , MD7,8; Olof Stahl, MD9; Enrique Gonzalez-Billalabeitia , MD10,11; Ugo De Giorgi , MD12; Stéphane Culine , MD13; Ronald de Wit, MD14; Aaron R. Hansen , MD15; Marko Bebek , MD16; Angelika Terbuch, MD17; Costantine Albany, MD18; Marcus Hentrich, MD19; Jourik A. Gietema , MD20; Helene Negaard , MD21; Robert A. Huddart , MD22; Anja Lorch, MD23,24; Fay H. Cafferty , PhD25; Daniel Y. C. Heng , MD26; Christopher J. Sweeney , MD27; Eric Winquist, MD28; Michal Chovanec , MD29; Christian Fankhauser , MD30; Daniel Stark, MD31; Peter Grimison , MD32; Andrea Necchi , MD33; Ben Tran, MD34; Axel Heidenreich, MD35; Jonathan Shamash, MD36; Cora N. Sternberg , MD37; David J. Vaughn, MD38; Ignacio Duran , MD39; Carsten Bokemeyer , MD40; Anna Patrikidou, MD41; Richard Cathomas , MD42; Samson Assele, MSc2; and Silke Gillessen , MD43,44,45 for the International Germ Cell Cancer Classification Update Consortium

doi : 10.1200/JCO.20.03292

Journal of Clinical Oncology 39, no. 14 (May 10, 2021) 1553-1562.

The classification of the International Germ-Cell Cancer Collaborative Group (IGCCCG) has been a major advance in the management of germ-cell tumors, but relies on data of only 660 patients with seminoma treated between 1975 and 1990. We re-evaluated this classification in a database from a large international consortium.

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Predicting Outcomes in Men With Metastatic Nonseminomatous Germ Cell Tumors (NSGCT): Results From the IGCCCG Update Consortium

Silke Gillessen , MD1,2,3; Nicolas Sauvé , MSc4; Laurence Collette , PhD4; Gedske Daugaard , MD5; Ronald de Wit, MD6; Costantine Albany, MD7; Alexey Tryakin , MD8,9; Karim Fizazi , MD10; Olof Stahl, MD11; Jourik A. Gietema , MD12; Ugo De Giorgi , MD13; Fay H. Cafferty , PhD14; Aaron R. Hansen , MD15; Torgrim Tandstad, MD16; Robert A. Huddart , MD17; Andrea Necchi , MD18; Christopher J. Sweeney , DM19; Xavier Garcia-Del-Muro , MD20; Daniel Y. C. Heng , MD21; Anja Lorch, DM22,23; Michal Chovanec , MD24; Eric Winquist, MD25; Peter Grimison , MD26; Darren R. Feldman , MD27,28; Angelika Terbuch, MD29; Marcus Hentrich , MD30; Carsten Bokemeyer , MD31; Helene Negaard , MD32; Christian Fankhauser , MD33; Jonathan Shamash, MD34; David J. Vaughn, MD35; Cora N. Sternberg , MD36; Axel Heidenreich, MD37; and J?rg Beyer , MD38; for the International Germ Cell Cancer Classification Update Consortium

doi : 10.1200/JCO.20.03296

Journal of Clinical Oncology 39, no. 14 (May 10, 2021) 1563-1574.

The classification of the International Germ Cell Cancer Collaborative Group (IGCCCG) plays a pivotal role in the management of metastatic germ cell tumors but relies on data of patients treated between 1975 and 1990.

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Eprenetapopt Plus Azacitidine in TP53-Mutated Myelodysplastic Syndromes and Acute Myeloid Leukemia: A Phase II Study by the Groupe Francophone des Myélodysplasies (GFM)

Thomas Cluzeau , MD, PhD1,2,3; Marie Sebert, MD, PhD3,4; Ramy Rahmé , MD3,4; Stefania Cuzzubbo , MD, PhD5; Jacqueline Lehmann-Che , MD6; Isabelle Madelaine, PharmD6; Pierre Peterlin , MD3,7; Blandine Bève, PhD3; Habiba Attalah, PhD3; Fatiha Chermat, PhD3; Elsa Miekoutima, MD4; Odile Beyne Rauzy, MD, PhD3,8; Christian Recher , MD, PhD3,8; Aspasia Stamatoullas, MD3,9; Lise Willems, MD3,10; Emmanuel Raffoux, MD3,4; Céline Berthon, MD3,11; Bruno Quesnel, MD, PhD3,11; Michael Loschi, MD, PhD1,2; Antoine F. Carpentier , MD, PhD5; David A. Sallman , MD12; Rami Komrokji , MD12; Anouk Walter-Petrich, PhD13; Sylvie Chevret , PhD13; Lionel Ades, MD, PhD3,4; and Pierre Fenaux, MD, PhD3,4

doi : 10.1200/JCO.20.02342

Journal of Clinical Oncology 39, no. 14 (May 10, 2021) 1575-1583.

TP53-mutated (TP53m) myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) have very poor outcome irrespective of the treatment received, including 40% responses (20% complete remission [CR]) with azacitidine (AZA) alone, short response duration, and a median overall survival (OS) of approximately 6 months. Eprenetapopt (APR-246), a novel first-in-class drug, leads to p53 protein reconformation and reactivates its proapoptotic and cell-cycle arrest functions.

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Eprenetapopt (APR-246) and Azacitidine in TP53-Mutant Myelodysplastic Syndromes

David A. Sallman , MD1; Amy E. DeZern, MD2; Guillermo Garcia-Manero , MD3; David P. Steensma , MD4; Gail J. Roboz , MD5; Mikkael A. Sekeres , MD, MS6; Thomas Cluzeau , MD, PhD7; Kendra L. Sweet, MD1; Amy McLemore , MS1; Kathy L. McGraw, PhD1; John Puskas, PhD1; Ling Zhang, MD1; Jiqiang Yao, PhD8; Qianxing Mo , PhD8; Lisa Nardelli, BS1; Najla H. Al Ali, MSc1; Eric Padron , MD1; Greg Korbel, PhD9; Eyal C. Attar, MD9; Hagop M. Kantarjian, MD3; Jeffrey E. Lancet, MD1; Pierre Fenaux, MD, PhD10; Alan F. List, MD1and Rami S. Komrokji , MD1

doi : 10.1200/JCO.20.02341

Journal of Clinical Oncology 39, no. 14 (May 10, 2021) 1584-1594.

Approximately 20% of patients with TP53-mutant myelodysplastic syndromes (MDS) achieve complete remission (CR) with hypomethylating agents. Eprenetapopt (APR-246) is a novel, first-in-class, small molecule that restores wild-type p53 functions in TP53-mutant cells.

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Drugging the Master Regulator TP53 in Cancer: Mission Possible?

Giovanni Blandino, MD1

doi : 10.1200/JCO.21.00192

Journal of Clinical Oncology 39, no. 14 (May 10, 2021) 1595-1597.

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Surgical Perspective on Sentinel Node Biopsy for Operable T1-T2N0 Oral and Oropharyngeal Cancer

Nir Hirshoren , MD and Jeffrey M. Weinberger, MD

doi : 10.1200/JCO.20.03300

Journal of Clinical Oncology 39, no. 14 (May 10, 2021) 1598-1599.

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What Is the Acceptable Noninferiority Limit for Nodal Recurrences When Ascertaining Sentinel Lymph Node Biopsy as an Alternative to Neck Dissection for Early Oral and Oropharyngeal Cancers?

Deep Chakrabarti , MD, Naseem Akhtar , MS, MCh, Shiv Rajan , MS, MCh, Sumaira Qayoom , MD, Vijay Kumar , MS, MCh, Arun Chaturvedi, MS, MAMS, Mranalini Verma , MD, Rajeev Gupta, MD, Madan Lal Brahma Bhatt, MD, and Shirin Parveen, DNB

doi : 10.1200/JCO.20.03439

Journal of Clinical Oncology 39, no. 14 (May 10, 2021) 1599-1600.

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Reply to N. Hirshoren et al and D. Chakrabarti et al

Stephen Y. Lai , MD, PhD and Robert L. Ferris , MD, PhD

doi : 10.1200/JCO.21.00027

Journal of Clinical Oncology 39, no. 14 (May 10, 2021) 1600-1601.

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Erratum

doi : 10.1200/JCO.21.00886

Journal of Clinical Oncology 39, no. 14 (May 10, 2021) 1602-1602.

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