Journal of Clinical Oncology

Josep Tabernero, MD, PhD1; Axel Grothey, MD2; Eric Van Cutsem, MD, PhD3; Rona Yaeger, MD4; Harpreet Wasan, MD5; Takayuki Yoshino, MD, PhD6; Jayesh Desai, MBBS7; Fortunato Ciardiello, MD, PhD8; Fotios Loupakis, MD, PhD9; Yong Sang Hong, MD, PhD10; Neeltje Steeghs, MD, PhD11; Tormod Kyrre Guren, MD, PhD12; Hendrik-Tobias Arkenau, MD, PhD13; Pilar Garcia-Alfonso, MD14; Elena Elez, MD, PhD1; Ashwin Gollerkeri, MD15; Kati Maharry, PhD15; Janna Christy-Bittel, MSN15; and Scott Kopetz, MD, PhD16

doi : 10.1200/JCO.20.02088

Journal of Clinical Oncology 39, no. 4 (February 01, 2021) 273-284.

BEACON CRC evaluated encorafenib plus cetuximab with or without binimetinib versus investigators' choice of irinotecan or FOLFIRI plus cetuximab in patients with BRAFV600E–mutant metastatic colorectal cancer (mCRC), after progression on 1-2 prior regimens. In the previously reported primary analysis, encorafenib, binimetinib plus cetuximab (ENCO/BINI/CETUX; triplet) and encorafenib plus cetuximab (ENCO/CETUX; doublet) regimens improved overall survival (OS) and objective response rate (ORR; by blinded central review) versus standard of care. The purpose of this analysis was to report updated efficacy and safety data.

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Randomized Trial of Irinotecan and Cetuximab With or Without Vemurafenib in BRAF-Mutant Metastatic Colorectal Cancer (SWOG S1406)

Scott Kopetz, MD, PhD1; Katherine A. Guthrie, PhD2; Van K. Morris, MD1; Heinz-Josef Lenz, MD3; Anthony M. Magliocco, MD4; Dipen Maru, MD1; Yibing Yan, PhD5; Richard Lanman, MD6; Ganiraju Manyam, PhD1; David S. Hong, MD1; Alexey Sorokin, PhD1; Chloe E. Atreya, MD7; Luis A. Diaz, MD8; Carmen Allegra, MD9; Kanwal P. Raghav, MD1; Stephen E. Wang, MD10; Christopher H. Lieu, MD11; Shannon L. McDonough, MS2; Philip A. Philip, MD12; and Howard S. Hochster, MD13

doi : 10.1200/JCO.20.01994

Journal of Clinical Oncology 39, no. 4 (February 01, 2021) 285-294.

BRAFV600E mutations are rarely associated with objective responses to the BRAF inhibitor vemurafenib in patients with metastatic colorectal cancer (CRC). Blockade of BRAFV600E by vemurafenib causes feedback upregulation of EGFR, whose signaling activities can be impeded by cetuximab.

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Total Body Irradiation or Chemotherapy Conditioning in Childhood ALL: A Multinational, Randomized, Noninferiority Phase III Study

Christina Peters, MD1; Jean-Hugues Dalle, MD, PhD2; Franco Locatelli, MD, PhD3; Ulrike Poetschger, PhD4; Petr Sedlacek, MD5; Jochen Buechner, MD, PhD6; Peter J. Shaw, MD7; Raquel Staciuk, MD8; Marianne Ifversen, MD, PhD9; Herbert Pichler, MD1; Kim Vettenranta, MD, PhD10; Peter Svec, MD, PhD11; Olga Aleinikova, MD, PhD12; Jerry Stein, MD13; Tayfun Güng?r, MD14; Jacek Toporski, MD15; Tony H. Truong, MD, MPH16; Cristina Diaz-de-Heredia, MD17; Marc Bierings, MD, PhD18; Hany Ariffin, MD, PhD19; Mohammed Essa, MD20; Birgit Burkhardt, MD, PhD21; Kirk Schultz, MD22; Roland Meisel, MD23; Arjan Lankester, MD, PhD24; Marc Ansari, MD25; and Martin Schrappe, MD, PhD26 on behalf of the IBFM Study Group; Arend von Stackelberg, MD27 on behalf of the IntReALL Study Group; Adriana Balduzzi, MD28 on behalf of the I-BFM SCT Study Group; Selim Corbacioglu, MD29 on behalf of the EBMT Paediatric Diseases Working Party; and Peter Bader, MD30

doi : 10.1200/JCO.20.02529

Journal of Clinical Oncology 39, no. 4 (February 01, 2021) 295-307.

Total body irradiation (TBI) before allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients with acute lymphoblastic leukemia (ALL) is efficacious, but long-term side effects are concerning. We investigated whether preparative combination chemotherapy could replace TBI in such patients.

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Metachronous Contralateral Testicular Cancer in the Cisplatin Era: A Population-Based Cohort Study

Ragnhild Hellesnes, MD1,2; Tor ?ge Myklebust, PhD3,4; Roy M. Bremnes, MD, PhD1,2; ?sa Karlsdottir, MD, PhD5; ?ivind Kvammen, MD6; Helene F. S. Negaard, MD, PhD7; Torgrim Tandstad, MD, PhD8,9; Tom Wilsgaard, PhD10; Sophie D. Foss?, MD, PhD4,7,11; and Hege S. Haugnes, MD, PhD1,2

doi : 10.1200/JCO.20.02713

Journal of Clinical Oncology 39, no. 4 (February 01, 2021) 308-318.

It is hypothesized that cisplatin-based chemotherapy (CBCT) reduces the occurrence of metachronous contralateral (second) germ cell testicular cancer (TC). However, studies including treatment details are lacking. The aim of this study was to assess the second TC risk, emphasizing the impact of previous TC treatment.

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Dose-Dependent Effect of Platinum-Based Chemotherapy on the Risk of Metachronous Contralateral Testicular Cancer

Joost M. Blok, MD1,2; Harmke J. Groot, MSc3; Eline H. Huele, MD1; Ronald de Wit, MD, PhD4; Simon Horenblas, MD, PhD2; Janine Nuver, MD, PhD5; Gerard Groenewegen, MD, PhD6; J.L.H. Ruud Bosch, MD, PhD1; J. Alfred Witjes, MD, PhD7; Jacqueline M. Tromp, MD, PhD8; Peter J.M. de Brouwer, MD, PhD9; Hetty A. van den Berg, MD10; Ben G.L. Vanneste, MD, PhD11; Tineke J. Smilde, MD, PhD12; Maureen J.B. Aarts, MD, PhD13; Jourik A. Gietema, MD, PhD5; Richard P. Meijer, MD, PhD1; and Michael Schaapveld, PhD3

doi : 10.1200/JCO.20.02352

Journal of Clinical Oncology 39, no. 4 (February 01, 2021) 319-327.

Patients with testicular germ cell tumor (TGCT) are at increased risk of developing a contralateral TGCT (CTGCT). Although some studies suggest that prior treatment with platinum-based chemotherapy affects CTGCT risk, a relationship between CTGCT risk and platinum dose has not previously been assessed. We analyzed the association between the number of platinum-based chemotherapy cycles and CTGCT risk.

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Cardiac Safety of Osimertinib: A Review of Data

Michael S. Ewer, MD, JD, PhD1; Sri Harsha Tekumalla, MSc2; Andrew Walding, MSc3; and Kwame N. Atuah, PhD2

doi : 10.1200/JCO.20.01171

Journal of Clinical Oncology 39, no. 4 (February 01, 2021) 328-337.

Osimertinib is a third-generation, CNS-active, irreversible, oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that potently and selectively inhibits both EGFR-TKI-sensitizing and T790M resistance mutations. We assess the cardiac failure risk in patients receiving osimertinib by evaluating the available data.

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