Dr. David Raben, vice president of Global Development, Oncology, and Dr. Sumita Bhatta, vice president and Global Medical Therapeutic Area Head, Oncology, connected to discuss how Amgen is advancing research to bring the promise of precision medicine and innovative immunotherapies to more patients with tough-to-treat forms of cancer.
Q: What is the importance of precision medicine in the treatment of cancer?
Raben: Precision medicine has driven a revolution in cancer treatment for some patients, providing new therapeutic approaches that are tailored to the unique biology of patients’ tumors. While we are beginning to move past the days of one-size-fits-all treatment with the development of new therapies that target specific cancer-causing proteins, the majority of patients are still not eligible for targeted medicines.1 Additionally, there is variation in patients’ responses to current precision cancer medicines that may be attributable to heterogeneity within tumors containing co-mutations or emerging mutations, which requires clever new strategies such as combining cooperative or synergistic therapies to help improve duration of response and prevent or overcome drug resistance.
The discovery of new targets and biomarkers has set the stage for us to expand precision oncology strategies into new cancers and, by doing so, potentially benefit more patients. Currently, we are advancing two late-stage programs in certain types of small cell lung cancer (SCLC) as well as gastric and gastroesophageal junction (GEJ) cancers, leveraging this biomarker-driven approach. We are energized to evaluate opportunities to apply this strategy to earlier stages of lung and gastrointestinal cancers.
Q: Patients diagnosed with SCLC or gastric cancer often face a poor prognosis. Why?
Bhatta: These are often complex, aggressive cancers, and several factors impact why patients face a poor prognosis at present. SCLC is an aggressive, fast-growing lung cancer. Roughly two-thirds of patients present with advanced disease at the time of diagnosis,2 and treatment options are limited with no currently approved therapies for patients in the third line, who have experienced disease progression on multiple treatments.
Gastric cancer currently ranks fourth in cancer-related mortality worldwide, and in the western world, it is most often diagnosed at an advanced stage.3 Once it spreads, survival rates fall dramatically.4 Gastroesophageal cancers, though less common in the U.S. than in Asia, accounted for more than 26,000 deaths in the U.S. in 2021.5 While certain patients with HER2 gene overexpression have a targeted treatment option, and treatment progress continues to expand, historically the standard of care for most gastric cancer patients has been chemotherapy, which offers less than a year of benefit in terms of median overall survival.5
Q: How is the treatment landscape changing for these patients?
Bhatta: The emergence of precision medicine, new targeted approaches, and innovative immunotherapies could dramatically impact treatment options. Biomarkers play an important role in making sure the right patients are treated with the right drug. For instance, HER2 is a well-recognized therapeutic target in gastric cancer, meanwhile, therapies that target FGFR2b could mark another advancement in the field.5 The protein is overexpressed in about 30% of gastric and GEJ cancers and is associated with a poor prognosis, which makes it a particularly compelling target.6 We have several clinical trials underway investigating a monoclonal antibody targeting patients with gastric or GEJ cancers that express this specific protein.
Raben: There is also encouraging potential to address the unmet needs of patients in SCLC. For years, SCLC was not well understood. Thanks to advancing science, that is changing with substantial scientific discoveries elucidating subtypes within SCLC demonstrating different phenotypic characteristics. The target we’re pursuing, known as DLL3, is expressed at very low levels within normal tissues; however, in more than 80% of SCLC tumors, it is expressed on the cell surface at high levels. This provides a potential approach to treat an aggressive cancer in a targeted manner with T-cell engagers. These therapies harness the body’s own immune system to target specific proteins on the surface of cancer cells – allowing the T cells to recognize the tumor more readily, rather than turning on the entire immune cascade. In SCLC, we are investigating a T-cell engager that targets DLL3 in several clinical trials across several lines of therapy.
Q: Where do you see treatment paradigms for gastric/GEJ cancer and SCLC in 20 years? What role will Amgen play in these advances?
Bhatta: At Amgen Oncology, we are driven by the belief that we can do more for people living with cancer by delivering a spectrum of cancer treatment options that address wide-ranging patient needs. To do that, we are embracing precision medicine by leveraging revolutionary biomarkers, exploring targeted approaches, and harnessing the power of the immune system and deep knowledge of the human and cancer genome to drive innovation. We are dedicated to continuing our work in collaboration with partners across the healthcare ecosystem to make more breakthroughs a reality for patients as soon as possible.
To learn more about Amgen’s work with precision medicine and immunotherapies in tough-to-treat cancers, visit AmgenOncology.com.
1. Haslam A, et al. Updated estimates of eligibility for and response to genome-targeted oncology drugs among US cancer patients, 2006-2020. Ann Oncol. 2021;32(7):926-932.
2. American Cancer Society. Small Cell Lung Cancer Stages. https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/staging-sclc.html. Accessed September 20, 2022.
3. Digklia A, et al. Advanced gastric cancer: Current treatment landscape and future perspectives. World J Gastroenterol. 2016;22(8):2403-14.
4. American Cancer Society. Stomach Cancer Survival Rates. https://www.cancer.org/cancer/stomach-cancer/detection-diagnosis-staging/survival-rates.html.
5. Sonbol MB, et al. The Treatment Landscape for Gastroesophageal Adenocarcinomas. Clin Adv Hematol Oncol. 2022;20(3):169-177.
6. Catenacci D, et al. Presented at: American Society of Clinical Oncology Gastrointestinal Cancer Symposium; May 20, 2021; Online Virtual Scientific Program. Abstract 4010.