“Pepe” Baselga, MD, Phd: in Memoriam (1959–2021) Josep Tabernero1, David M

Published OnlineFirst April 21, 2021; DOI: 10.1158/2159-8290.CD-21-0458

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Obituary José “Pepe” Baselga, MD, PhD: In Memoriam (1959–2021) Josep Tabernero1, David M. Hyman2, and Jean-Charles Soria3

On March 21, 2021, a guiding displayed signs of the visionary leader he would later become. light in cancer research and clin- His passion and dedication to unmasking the basic mecha- ical oncology and valiant trans- nisms of cancer and improving patient care drove him to former of patient treatment challenge the way research was conducted. and care was extinguished. José Spurred by his father’s encouragement to travel in order Baselga’s untimely passing has to fulfill his aspirations to become a transformative figure sent shockwaves through the in oncology, he left Spain for the United States to join the global cancer research commu- Memorial Sloan Kettering Cancer Center (MSKCC) in New nity. We have lost a true giant—a York, NY. There, he completed his oncology training under visionary leader in translational the mentorship of John Mendelsohn and Larry Norton in the science and precision oncology laboratory and clinic, respectively. As early as 1991, José had and one who also transformed begun to carve out a new paradigm for cancer research. In institutions and professional conducting related clinical and laboratory research in paral- societies everywhere he went. lel, José would embody what later became known as “transla- As we reflect on some of José’s many remarkable achieve- tional” research many years before the term was coined and ments as well as the many qualities that made him the unique popularized. During his almost six-year tenure at MSKCC, individual he was, we hope to do him justice. This is the first José conducted preclinical studies in parallel to leading a clin- obituary published in Cancer Discovery, a journal for which ical trial to test the potential therapeutic effects of the first he served as a founding Editor-in-Chief along with Editor-in- anti-HER2 monoclonal antibody that would later be known Chief Lewis C. Cantley. The irony is bittersweet: José was an as trastuzumab. As is now universally known, the efficacy of undisputed man of “firsts” whom we all followed, trying to this molecule in treating patients with breast cancer overex- keep up with his trailblazing pace, frightening brilliance, and pressing HER2 exceeded all expectations (except José’s) and steadfast determination to improve outcomes for patients transformed the natural history of this disease. Thousands with cancer everywhere. of patients’ lives have been saved, thanks to these innovations José Baselga was born on July 3, 1959, in Barcelona, Spain, José pioneered during his oncology fellowship. with the pursuit of excellence in health care quite literally in Returning to the Vall d’Hebron Hospital in 1996 to lead his blood. His mother was a nurse, and both his father and its then very small Oncology Department, José’s vision, grandfather were physicians. “Medicine runs in our family work ethic, and commitment to accelerate better treatment like an autosomal dominant trait,” said his youngest sister options for patients quickly lifted the department to new Eulalia, herself a pediatric dermatologist at the San Joan de heights, eventually reaching the top echelon of interna- Deu Hospital in Barcelona, during a recent tribute for her tional cancer centers. José created an environment in which late brother. Like his younger sister, José was destined to be optimal patient care was tightly integrated with innovative a devoted physician and healer who spent his life caring for translational research, all in the context of a Public Health patients with cancer. During his outstanding 27-year career, System—an exemplary model that has been adopted and José produced a remarkable string of milestones in transla- adapted across borders. tional and clinical cancer research that have echoed interna- José hated wasting time. He applied his sense of deter- tionally in the battle against cancer. mined urgency to everything he did. He made the impossible Even during his early days as a resident in Internal Medi- seem easy. His colleagues looked at him in astonishment cine at Vall d’Hebron University Hospital in Barcelona, José when he matter-of-factly declared that his oncology program would occupy two entire floors at Vall d’Hebron. In spite of a traditionally rigid environment, José succeeded in creating 1Vall d’Hebron Hospital Campus and Institute of Oncology (VHIO), UVic- an Oncology Department to incorporate the best cancer care 2 UCC, Barcelona, Spain. Loxo Oncology and Eli Lilly, Stamford, Connecti- with a translational–clinical research program, uniting all cut. 3Paris-Saclay University and Gustave Roussy Cancer Campus, Villejuif, France. professionals involved in cancer care. This emboldened José to create the Vall d’Hebron Institute of Oncology (VHIO), Corresponding Author: Josep Tabernero, Medical Oncology Department, Vall d’Hebron University Hospital, Passeig Vall d’Hebron 119–129, Barce- which has since become a comprehensive cancer center of lona 08035, Spain. Phone: 34 93 489 4301; Fax: 34 93 274 6059; E-mail: international acclaim. José was therefore able to turn his [email protected] unique vision into a reality. Aided by direct access to patients Cancer Discov 2021;11:1614–6 and his multidisciplinary translational model, VHIO rapidly doi: 10.1158/2159-8290.CD-21-0458 became one of the few cancer research institutes to translate ©2021 American Association for Cancer Research research findings for the benefit of patients in record time.

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Seeking out new challenges, José crossed the pond once function on a new path and spearheaded the acceleration of again to join the Massachusetts General Hospital Cancer therapeutic development and implemented new directions to Center in Boston as Chief of the Division of Hematology and advance research into epigenetics, antibody–drug conjugates, Oncology in 2010. Although initially intending a longer ten- cell-based therapies, and other novel anticancer medicines. ure in Boston, José could not pass up the unexpected oppor- In what would turn out to be a final example of his incom- tunity to return to MSKCC in 2013 as its Physician-in-Chief parable ability to forge powerful partnerships by bringing the and subsequently its Chief Medical Officer. In his perch atop right people together at the right time, José was instrumen- MSKCC’s leadership, José further elevated MSKCC’s already tal in establishing a collaboration between AstraZeneca and formidable international prestige. In addition to creating Daiichi Sankyo, which led to the recent US and EU approval a fully integrated program in precision medicine, he also of the antibody–drug conjugates trastuzumab deruxtecan founded the Center for Molecular Oncology and Early Drug and datopotamab deruxtecan as novel precision therapies. Development service, and broke new ground by setting up a Trastuzumab deruxtecan has since received global approv- comprehensive molecular profiling program, accessible to all als for HER2-positive breast and gastric cancers, with patients at MSKCC. multiple additional indications anticipated in the coming Throughout his career, José was a change-maker in the years. Always steps ahead, we keenly await the results of development of molecular targeted agents, with special José’s ongoing projects as well as those that were surely emphasis on breast cancer. He directed several preclinical being planned. Some of these will certainly center on his and early clinical studies that contributed to the develop- quest to combat resistance to cancer therapies and apply ment of agents against the epidermal growth factor receptor real-world evidence and digital technologies to innovative (EGFR) as well as the HER2 receptor and the PI3K pathway, clinical trial design. among others. These therapies would become global stand- In addition to his numerous achievements and seminal ards of care for patients with cancer worldwide. One early contributions to oncology research, José was a truly charis- and notable example was José’s contributions to developing matic character with limitless generosity, especially for his the first EGFR-targeted therapies. Initially working on what beloved patients. Above and beyond his role as a gifted physi- would become the precursor to cetuximab in the Mendelsohn cian, he sought to ease his patients’ fears and preoccupations laboratory during his fellowship, José would go on to help by gently advocating aliveness. He was an amazing human lead the clinical development of cetuximab, the first EGFR- being with tremendous heart. targeted monoclonal antibody for the treatment of colorectal Across Europe, North America, and beyond, patients, and head and neck cancers. In pursuing this line of scientific mentees, colleagues, and professional societies continuously and clinical inquiry, José had again bucked conventional wis- sought his counsel and collaboration. José always responded dom that this approach would not succeed, and in doing so to these requests with equal measures of motivation, dedica- would significantly improve outcomes for patients with these tion, and heart. José was a devoted mentor; he helped to build refractory cancers. the careers of countless young talents who showed the same Although molecular-based therapies have provided levels of ambition, dedication, and tenacity that he expected substantial clinical benefit for patients with cancer, their from himself. We were three of his disciples, and, like many effectiveness is often limited by either primary or acquired who followed, are hugely indebted to him. resistance. José and collaborators identified novel treatment He was also a man of intensity who dismissed medioc- combinations, demonstrating that incorporation of a second rity point blank. He sought answers and did not always anti-HER2 monoclonal antibody, pertuzumab, with a unique take kindly to those who answered his questions by posing binding mode into trastuzumab-based regimens could fur- one of their own. In his storm, he took down trees and did ther prolong benefit and delay or reverse drug resistance. not make excuses for this behavior. While he could be very José would later demonstrate that this combination would demanding of his colleagues, we all appreciated and ben- also improve upon the cure rate of patients with early-stage efited enormously by being held to such high standards. HER2-positive breast cancer. These clinical trials represent José helped to build the careers of a generation of oncolo- some of the most groundbreaking studies in the history of gists and physicians. He inspired his mentees through his HER2-positive breast cancer. own indomitable spirit and drove each of them to move In addition to his contributions to the development of tras- forward and subsequently continue to achieve the very best tuzumab, pertuzumab, and cetuximab, José was involved in of themselves. José had an unmatched gift to push his men- the development of at least a dozen approved cancer drugs and tees to the limits of their own intelligence and medical and precision therapies. These include everolimus, trastuzumab scientific intuition. emtansine, lapatinib, gefitinib, erlotinib, neratinib, olaparib, Throughout his career, many consortia of excellence and alpelisib, and, most recently, trastuzumab deruxtecan. scientific societies rightly sought—and counted on—his sci- José’s final leadership position would be one that he pur- entific expertise, top-draw talent, and leadership. Concern- sued with equal vigor, zeal, and driving spirit until almost his ing the latter, he was a long-time volunteer of the American final days. After resigning from MSKCC in 2018, José soon Society of Clinical Oncology (ASCO) and served on its Board embraced a new challenge, serving as AstraZeneca’s Execu- of Directors (2003–2006), Annual Meeting Scientific Program tive Vice President of Oncology Research and Development Committee (which he chaired in 2001), and Special Awards and Member of its Senior Executive Committee. In typi- Selection Committee, among other roles. cal whirlwind style, José immediately set about innovating. José also served as President of the European Society for Medi- He set the company’s Oncology Research and Development cal Oncology (ESMO; 2008–2009), and the American Association

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Views for Cancer Research (AACR; 2015–2016). He transformed both globe. It now falls on our shoulders, as a community, to col- by making fundamental changes and adding innovative pro- lectively build on his incredible legacy, one which will live on grams, mainly focused on better supporting, nurturing, and for decades to come. guiding future generations of thought leaders within the oncol- José Baselga, you remain unforgettable in every way. ogy field, and more rapidly evolving translational cancer science and clinical oncology. “All of us at AACR are deeply saddened Authors’ Disclosures by the loss of José, our dear colleague and friend. His death is J. Tabernero reports personal fees from Array Biopharma, Astra- a profound loss to the entire national and international cancer Zeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, Daiichi San- research community. He was a major force at AACR. Under his kyo, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, visionary leadership as President, AACR had a year of tremen- Hutchison MediPharma International, Ikena Oncology, IQVIA, Lilly, dous growth in innovative programs and initiatives. He also Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, played a leading role in strategically laying the foundation of Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung our future scientific programs. He was a great communicator Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics and TheraMyc and personal fees from Imedex, Medscape Education, with an extraordinary intellect, and he consistently inspired us at MJH Life Sciences, PeerView Institute for Medical Education and AACR with his characteristic work ethic, his passion for helping Physicians Education Resource (PER) outside the submitted work. cancer patients, and his tremendous kindness,” said Margaret D.M. Hyman reports personal fees from Lilly/Loxo Oncology outside Foti, AACR’s Chief Executive Officer. the submitted work. J.-C. Soria reports other support from Astra- Above all, José was devoted to his adored wife Silvia, and Zeneca, Hookipa Pharmaceutical, Relay Therapeutics, and Gritstone much loved as “Papi” to his four children, Marc, Clara, Pepe, Oncology during the conduct of the submitted work. and Alex. José’s passing represents an unfillable void to his family, loved ones, and friends. Acknowledgment He will continue to inspire present and future generations We are grateful to Amanda Wren (VHIO) for her contribution to of cancer researchers and clinical investigators around the compiling this tribute.

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José ''Pepe'' Baselga, MD, PhD: In Memoriam (1959−2021)

Josep Tabernero, David M. Hyman and Jean-Charles Soria

Cancer Discov 2021;11:1614-1616. Published OnlineFirst April 21, 2021.

Updated version Access the most recent version of this article at: doi:10.1158/2159-8290.CD-21-0458

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