Driving Innovation to Make a Difference in Head and Neck Cancers

David G. Pfister, MD, felt a special pull toward medicine as a potential career from an early age. This interest was instilled by his mother, who was a chemistry major, went to the University of Pennsylvania to study physical therapy, and then served during the polio epidemic.

He remembers her passing along stories of caring for patients during this time, and one grateful family sending thank-you chocolates during the holidays for years. That early interest set him on the path to medicine and ultimately a career as a head and neck oncologist widely known for his pioneering work in the development of combined modality, organ-preservation treatment programs, among other accomplishments, making him a Giant of Cancer Care in head and neck cancers.

Pfister was born in Rhode Island and grew up outside of New Haven, Connecticut, with 3 siblings. For his undergraduate studies, Pfister attended Dartmouth College in Hanover, New Hampshire, earning his degree in biochemistry in 1977.

After completing his degree, Pfister followed in his mother’s footsteps to the University of Pennsylvania in Philadelphia and attended medical school there. During one of his clinical rotations while a resident at the Hospital of the University of Pennsylvania, he connected with John H. Glick, MD, the director of the institution’s cancer center from 1985 to 2006 and a former president of the American Society of Clinical Oncology (ASCO), whom he credits with sparking his initial interest in oncology.

“I did an oncology rotation with John, and at that time I was [considering] cardiology or oncology,” Pfister recalled. “He was involved in a large cooperative group study called the Head and Neck Contracts Program, which was one of the first big studies evaluating chemotherapy in patients with head and neck cancer.¹ I still remember that connection now over 40 years [later], and I left residency thinking that I wanted to be an oncologist.”

After completing medical school and his residency in internal medicine, Pfister became a Robert Wood Johnson Clinical Scholar at Yale University in New Haven, receiving formal training in clinical epidemiology and mentoring from Alvan Feinstein, MD, a leader in that field. During his time at Yale, Pfister had a chance meeting with the woman who would become his wife while arriving at work about the same time as a mutual colleague.

“She was an attorney in government and community affairs at Yale’s medical school, and it was my next-to-last month in New Haven,” Pfister remembers. “I did not know my wife at the time, but we both knew our colleague. We just happened to arrive, park, meet in the parking lot, and one thing led to another after that. If I had stopped for a cup of coffee that day, it probably would have been a totally different outcome.”

Pfister went on to hold a medical oncology and hematology fellowship at Memorial Sloan Kettering Cancer Center (MSK) from 1987 to 1989, serving as chief fellow during his last year. He joined the faculty at the institution in 1989, and it was at MSK where he would make significant contributions to the field of head and neck cancer over the course of his illustrious career. He credits George Bosl, MD, as one of his important mentors during his career at MSK.

Putting Patient Quality of Life Front and Center

Pfister became the inaugural chief of the Head and Neck Oncology Service in 2004, including responsibilities as coleader of the multidisciplinary Head and Neck Cancer Disease Management team at MSK. He is also the codirector of the MSK Center for HPV-Related Cancers. He has been a senior first or coauthor on over 200 publications, with his works appearing in a spectrum of high-impact, peer-reviewed journals. He also serves on the board of directors of the National Comprehensive Cancer Network (NCCN) and is the chair of the NCCN’s Head and Neck Cancer Guidelines Panel.

Among his many accomplishments, Pfister is proudest of his contribution to the development, refinement, and adoption into standard practice of combined modality, organ preservation modality therapy that allows patients to maintain functionality and cosmesis without sacrificing efficacy. The approach has since become a standard of care alternative to primary surgery, initially allowing patients with advanced larynx cancer to avoid a total laryngectomy and maintain their natural voice, and then systematically expanding the applicability of the concept to other primary sites.

This journey began for him when he first published in 1991 as principal investigator a study demonstrating that larynx preservation with combined chemotherapy and radiation with surgery reserved for salvage was feasible and effective in patients with advanced, resectable squamous cell carcinoma of the head and neck.² In 1995, he was the lead author of a study that expanded the approach to patients with advanced oropharynx cancer.³ Pfister’s efforts contributed to the development of the TALK prognostic model for predicting larynx preservation outcomes. The model adds 1 point for each poor prognostic covariate present, including T stage, albumin levels, maximum alcohol use, and Karnofsky performance status.⁴ He also cochaired ASCO’s Practice Guideline Committee on the use of larynx-preservation strategies in the treatment of larynx cancer from 1996 to 2006, helping to provide evidence-based guidance for clinical practice.⁵

“When I started, surgery and radiation were basically what you did for curative treatment,” Pfister said. “[We developed] a program that integrated drug therapy and offered the potential to preserve form and function without compromising survival. If patients are able to avoid a potentially morbid operation, as long as you’re able to preserve survival, most will prefer that.”

Beyond organ preservation, Pfister participated in the development of cetuximab (Erbitux), work done in collaboration with José Baselga, MD, PhD, and John Mendelsohn, MD, for the treatment of patients with recurrent or metastatic head and neck squamous cell cancer.⁶ Additionally, he was first author on a paper integrating cetuximab with cisplatin and radiation therapy⁷ and was involved in further research to better understand the role of cetuximab as part of definitive treatment with radiation. Cetuximab was first approved by the FDA in 2006 for the treatment of patients with platinum-refractory recurrent or metastatic head and neck cancer and with radiation as part of definitive treatment. In November 2011, cetuximab was approved by the FDA in combination with platinum-based chemotherapy for the frontline treatment of patients with recurrent locoregional or metastatic squamous cell carcinoma of the head and neck.⁸ At the time of the approval, findings from the pivotal phase 3 EXTREME trial (NCT00122460) demonstrated that cetuximab was the first FDA-approved regimen in 30 years that extended overall survival in this patient population.

In another notable clinical trial, Pfister was among the investigators evaluating the safety and efficacy of pembrolizumab (Keytruda) in patients with cisplatin- and cetuximab-refractory head and neck cancer, demonstrating clinically meaningful activity in this patient population with a very poor prognosis.⁹

He was then the first author of a subsequent correlative science study published in 2023 that showed tumor mutational burden (TMB) and inflammatory biomarkers such as PD-L1 and T-cell–inflamed gene expression profile could be used to characterize responses to pembrolizumab in patients with head and neck cancers.¹⁰ Findings from the study revealed that TMB, PD-L1 combined positive score, and T-cell–inflamed gene expression profile were independently predictive of response to pembrolizumab, offering the potential of enhanced treatment individualization for patients and the avoidance of overtreatment.

Pfister has also made important contributions advancing therapeutics for other disease in the head and neck besides tumors of the upper aerodigestive tract. “When I started as [the] head and neck service chief in 2004, the potential role of drug therapy for thyroid and salivary cancers had received limited attention,” Pfister said. “In collaboration with MSK colleagues, our research programs in these diseases are now internationally recognized for their important contributions.” As a reflection of that, Pfister is the former chair of the Protocol Committee for the International Thyroid Oncology Group (ITOG), and other MSK faculty have served in leadership roles in that organization.

Pfister credits the environment at MSK and his love of his job and great colleagues for keeping him energized and ready to come to work each day. “I have been fortunate in having thoughtful and generous mentors throughout my career, and many colleagues who are not just collaborators, but friends, too. I am blessed with a devoted wife and loving family. Early in my career, one of my mentors said something to the effect of, ‘Happy at home, happy at work,’ [and that is] so true,” he said.

After 20 years as the inaugural chief of the Head and Neck Oncology Service at MSK, Pfister turned over the role to Alan Ho, MD, PhD, in September 2024.¹¹ Looking toward the future of cancer care in general, Pfister said that he is most enthusiastic about the potential positive effect that the growing wealth of knowledge of the biology of cancer will have on therapeutic advances.

He is also looking forward to seeing how advances in technology, such as artificial intelligence and wearable devices, will affect the cancer care continuum and related care models. In addition to his role with MSK, Pfister is chair of oncology at MediSys Jamaica Hospital in Queens, New York, an MSK affiliate, and is spearheading an effort to develop a cancer center for Queens at the safety-net health hospital.

Taking Time for Family and Traveling the World

Pfister lives in Westchester County, New York. Outside of medicine, he has a love for sports and enjoys spending time with his family. A former tennis state champion in his youth for the 12-year-old age group, Pfister doesn’t play as much as he used to, but avidly follows US Open happenings at nearby Flushing Meadows each year. He has 2 daughters who live in Washington, DC, and New York, whose passions led them to careers as an attorney and a software engineer.

In addition to tennis, Pfister enjoys hiking with his wife and traveling. “One of the challenges of being a medical provider is that it can be hard to get away. Hiking is something that we enjoy doing [together], is convenient, clears your head and there are a lot of great places around here to go,” he said.

Pfister’s career has afforded him the opportunity to travel to several destinations abroad that have left lasting impressions. He counts the Great Wall of China, St Petersburg in Russia, and the Vatican in Rome, Italy, as some of his favorites. Pfister said he also enjoys spending time in Austria in his capacity as a frequent course director of oncology seminars for physicians from countries in transition held twice a year in Salzburg as part of MSK’s collaboration with the Open Medical Institute program. Having studied abroad in Germany during his college years, Pfister tries to improve his German skills during these trips and in between them, and hopes to learn another foreign language at some point. Pfister considers himself an amateur historian and, in the future, he hopes to take more trips that can combine all his interests.

“Both of my daughters and my wife speak Spanish reasonably well,” Pfister said. “I would like to do some travel that combines [my love of] history, hiking, and language learning all tucked into one [trip].”

References

1. Adjuvant chemotherapy for advanced head and neck squamous carcinoma. Final report of the Head and Neck Contracts Program. Cancer. 1987;60(3):301-311. doi:10.1002/1097-0142(19870801)60:3<301::aid-cncr2820600306>3.0.co;2-v
2. Pfister DG, Strong E, Harrison L, et al. Larynx preservation with combined chemotherapy and radiation therapy in advanced but resectable head and neck cancer. J Clin Oncol. 1991;9(5):850-859. doi:10.1200/JCO.1991.9.5.850
3. Pfister DG, Harrison LB, Strong EW, et al. Organ-function preservation in advanced oropharynx cancer: results with induction chemotherapy and radiation. J Clin Oncol. 1995;13(3):671-680. doi:10.1200/JCO.1995.13.3.671
4. Sherman EJ, Fisher SG, Kraus DH, et al. TALK score: development and validation of a prognostic model for predicting larynx preservation outcome. Laryngoscope. 2012;122(5):1043-1050. doi:10.1002/lary.23220
5. American Society of Clinical Oncology, Pfister DG, Laurie SA, et al. American Society of Clinical Oncology clinical practice guideline for the use of larynx-preservation strategies in the treatment of laryngeal cancer. J Clin Oncol. 2006;24(22):3693-3704. doi:10.1200/JCO.2006.07.4559
6. Baselga J, Pfister D, Cooper MR, et al. Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin. J Clin Oncol. 2000;18(4):904-914. doi:10.1200/JCO.2000.18.4.904
7. Baselga J, Pfister D, Cooper MR, et al. Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin. J Clin Oncol. 2000;18(4):904-914. doi:10.1200/JCO.2000.18.4.904
8. Pfister DG, Su YB, Kraus DH, et al. Concurrent cetuximab, cisplatin, and concomitant boost radiotherapy for locoregionally advanced, squamous cell head and neck cancer: a pilot phase II study of a new combined-modality paradigm. J Clin Oncol. 2006;24(7):1072-1078. doi:10.1200/JCO.2004.00.1792
9. FDA approves Erbitux (cetuximab) for first-line recurrent locoregional or metastatic head and neck cancer in combination with platinum-based chemotherapy with 5-fluorouracil. News release. Eli Lilly and Company. November 7, 2011. Accessed August 4, 2025. https://investor.lilly.com/news-releases/news- release-details/fda-approves-erbituxr-cetuximab-first-line-recurrent
10. Bauml J, Seiwert TY, Pfister DG, et al. Pembrolizumab for platinum- and cetuximab-refractory head and neck cancer: results from a single-arm, phase II study. J Clin Oncol. 2017;35(14):1542-1549. doi:10.1200/JCO.2016.70.1524
11. Pfister DG, Haddad RI, Worden FP, et al. Biomarkers predictive of response to pembrolizumab in head and neck cancer. Cancer Med. 2023;12(6):6603-6614. doi:10.1002/cam4.5434
12. Alan Ho appointed chief of the head and neck oncology service at Memorial Sloan Kettering Cancer Center. News release. Memorial Sloan Kettering Cancer Center. September 13, 2024. Accessed August 4, 2025. https://www.mskcc.org/news- releases/alan-ho-appointed-chief-of-head-and-neck-oncology-service-at-msk-cancer