At MD Anderson, we work in partnership with our patients to enable groundbreaking research to better prevent, diagnose and treat cancer. Grounded in a culture of collaboration, connectivity, and data-based science, our research yields transformative findings that are shifting patient care and improving patients’ lives across the globe.
At the 2023 American Society of Clinical Oncology Annual Meeting, our experts will showcase their pacesetting research and join colleagues for discussion on the latest advances in oncology.
Below are highlights from our presentations, details about onsite networking opportunities with our experts and information on open positions at MD Anderson.
When AhR is activated, it causes immunosuppression and promotes growth of the malignant tumor. Researchers at MD Anderson and collaborators around the world have been conducting a Phase I clinical trial of a drug that can block AhR.
For the latest updates in soft tissue sarcoma treatment, we spoke with Neeta Somaiah, M.D., an associate professor who is a discussant and heavily featured in presentations on the latest sarcoma research at the ASCO Annual Meeting.
Hans Lee, M.D., explains BCMA and how it impacts clinical trials he is presenting at ASCO.
Meet the Experts
Visit booth 14030 to meet our experts and discuss hot topics in cancer research, learn about training and career opportunities and continue the conversation on key presentations. See the full schedule below.
Monday, June 5
Sunday, June 4
Saturday, June 3
Featured Research Presented at ASCO
Since the discovery of cyclin-dependent kinases (CDKs), a family of proteins vital in the early stages of cell development, scientists have tried to target them to disrupt the division and proliferation of cancer cells. This is especially true in breast cancer due to its reliance on this process for growth.
The first generation of these agents, known as CDK inhibitors, targeted both CDK4 and CDK6. That is why they’re known as CDK4/6 inhibitors.
One of the first Food and Drug Administration (FDA) approvals of a CDK4/6 inhibitor was based on the international, multicenter MONALEESA-7 and MONALEESA-2 clinical trials of ribociclib, which were led by MD Anderson’s Debu Tripathy, M.D., and Gabriel Horobagyi, M.D. The trials showed that, when given in combination with hormonal therapy, the inhibitor helped significantly extend the lives of breast cancer patients without disease progression.
Now, multiple CDK4/6 inhibitors are approved for breast cancer treatment. However, they have some shortcomings. Most breast cancer patients do not respond to them. Even among those that do, there are issues of toxicity and building resistance, which limit their effectiveness.
That’s why MD Anderson researchers remain focused on studying and developing CDK inhibitors. Soon, new research may solve those issues and help CDK inhibitors reach even more patients.
The next generation: Beyond CDK4/6
Timothy Yap, M.D., Ph.D., associate professor of Investigational Cancer Therapeutics, is leading three separate trials of CDK inhibitors that will be presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. He says we’re on the verge of seeing the next generation of CDK inhibitors.
“The question with CDK inhibitors has been, what’s next?” Yap says. “And what’s next is firstly a more selective and potent next-generation CDK4-specific inhibitor without blockade of the CDK6 target. By removing that, we’re seeing fewer toxicities, and we’re able to also dial up the dosage, which may make them more effective.”
One example is PF-07220060, a next-generation highly selective CDK4 inhibitor with significant sparing of CDK6 blockade.
“Because of its greater selectivity for CDK4 over CDK6, we see less neutropenia and, consequently, can dose higher to attain tolerated drug concentrations that exceed those reported for the approved dual CDK4/6 inhibitors,” says Yap. “Preclinical tumor models have shown that PF-07220060 effectively suppresses tumor growth in CDK4/6 inhibitor and endocrine therapy-resistant models.”
Yap says the early Phase I clinical trial data he is presenting are encouraging. These initial results suggest that these new CDK4 inhibitors are not only potentially better tolerated and more effective for new patients; they can also help overcome resistance in patients previously treated with CDK4/6 inhibitors.
Along with better targeting of CDK4, the next generation of CDK inhibitors is also taking aim at CDK2. Yap has been leading a Phase I trial of PF-07104091, which is a potent and novel CDK-2 selective inhibitor, as well as a study of BLU-222, a CDK2 inhibitor also under Phase I trial investigation. The justification for targeting CDK2 is based on research like the work being done in the lab of Khandan Keyomarsi, Ph.D., professor of Experimental Radiation Oncology.
“Robust preclinical research has shown that there are certain tumor types that have the potential for increased levels of certain biomarkers, such as cyclin E and CDK2 activity and/or loss of the Rb tumor suppressor,” Keyomarsi says.
The future of CDK combinations
These novel results open the door to several possibilities that Yap, Keyomarsi and others are currently exploring. In particular, the next-generation CDK4-selective or CDK2-selective agents in combination with endocrine therapy, respectively, showed promising antitumor activity in heavily pre-treated patients with hormone receptor positive, HER2 negative metastatic breast cancer who had stopped responding to their prior CDK4/6 inhibitor treatment and endocrine therapy.
Yap believes that a few years from now we’ll see greater use of these next-generation CDK4-selective and CDK2-selective drugs in different combination strategies in certain breast cancer patients.
Even larger possibilities are also on the horizon. For example, cyclin E is a protein that binds with CDK2 early in the cell cycle. When overexpressed, it has been shown to be a primary driver of cancer in patients across different tumor types.
“In pre-clinical models, inhibition of CDK2 showed anti-tumor activity in multiple cyclin E-aberrant cancer types,” Keyomarsi says. “Potentially leading to clinical strategies that could lead to the expansion of CDK2 inhibitor use in and beyond breast cancer.”
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Treatment with luspatercept improved red blood cell counts and erythroid responses compared to treatment with epoetin alfa in patients with myelodysplastic syndromes (MDS), allowing the majority to no longer require regular blood transfusions. Results from the Phase III COMMANDS trial, led by researchers at The University of Texas MD Anderson Cancer Center, were reported at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.
The study evaluated the efficacy and safety of first-line treatment with luspatercept, which enhances red blood cell maturation, compared with epoetin alfa, a therapy commonly used for low blood cell count, in transfusion-dependent patients with anemia due to very low- to intermediate-risk MDS.
In this interim analysis, 58.5% of patients receiving luspatercept achieved the primary endpoint of independence from red blood cell transfusions compared to 31.2% of patients who received epoetin alfa. Within the first 24 weeks of treatment transfusion, 47.6% of luspatercept patients achieved transfusion independence versus 29.2% of patients receiving epoetin alfa. Additionally, 74.1% of patients who received luspatercept saw hematologic improvement in erythroid responses greater than eight weeks, compared to 51.3% of patients who received epoetin alfa.
“Patients with myelodysplastic syndromes often experience anemia that requires frequent red blood cell transfusions,” said Guillermo Garcia-Manero, M.D., professor of Leukemia and lead investigator of the study. “In this study, we observed a significant improvement in patient red blood cell counts with luspatercept, representing a promising advance to enhance the lives of these patients.”
Myelodysplastic syndromes are a group of diseases in which the bone marrow doesn’t produce enough healthy blood cells, including red blood cells. Patients with MDS often experience symptoms such as anemia, fatigue, shortness of breath and increased vulnerability to infection.
Because of the frequency of anemia, most patients require regular red blood cell transfusions. Some cases of MDS can progress to acute myeloid leukemia (AML). Luspatercept is a novel agent that enables late-stage red blood cell maturation. By targeting the TGF-β signaling pathway, luspatercept helps restore normal red blood cell creation.
The trial enrolled 301 patients at 226 sites. Patients were randomized to receive subcutaneous luspatercept every three weeks or subcutaneous epoetin alfa weekly for 24 weeks. Patient characteristics were balanced across both treatment arms.
Treatment-related adverse events of all grades occurred in 30.3% of patients in the luspatercept group and 17.6% in the epoetin alfa group. Eight patients (4.5%) that received luspatercept discontinued treatment due to treatment-related adverse events. AML progression was reported in four patients receiving luspatercept and five patients receiving epoetin alfa. The safety profile was consistent with previous studies of the drug.
“These results show, for the first time, superior effectiveness of an innovative therapy over epoetin alfa,” Garcia-Manero said. “I am encouraged by these results, as luspatercept represents a transformative therapy that could become a new standard of care for patients with transfusion-dependent myelodysplastic syndromes.”
The patients in this study continue to be followed long term to determine overall survival, time of transfusion independence and frequency of progression to AML.
The study was funded by Bristol Myers Squibb. Garcia-Manero has worked in a consulting/advisory role for and received research support from Bristol Myers Squibb. A full list of co-authors and disclosures can be found here.
CHICAGO – Patients with early relapsed or refractory large B-cell lymphoma had significantly improved overall survival when treated with the chimeric antigen receptor (CAR) T cell therapy axicabtagene ciloleucel (axi-cel) when compared to the current standard-of-care chemoimmunotherapy, according to results of the Phase III ZUMA-7 trial reported by researchers from The University of Texas MD Anderson Cancer Center.
Data from the study were presented today by Jason Westin, M.D., director of clinical research in the Department of Lymphoma and Myeloma, at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting and published concurrently in the New England Journal of Medicine.
At a median follow-up of 47.2 months, axi-cel demonstrated a statistically significant improvement in overall survival (OS) over standard therapy. The median OS had not yet been reached for axi-cel, meaning more than half of the patients remained alive at the time of this analysis, compared to a median OS of 31.1 months on the control arm. The estimated four-year survival rate was 54.6% with axi-cel and 46% with standard care, corresponding to a 27.4% reduction in the risk of death with the cell therapy.
“This is the first randomized Phase III trial in nearly 30 years to improve overall survival with second-line curative therapy for patients with aggressive lymphoma. High-dose chemotherapy and stem cell transplant, the old standard, cured a small portion of patients but resulted in side effects for all,” Westin said. “The quality of life for patients treated with axi-cel improved faster than those treated with chemotherapy, and our results support axi-cel as a second-line treatment for these patients.”
B-cell lymphoma is a type of non-Hodgkin lymphoma that originates in the B cells. According to the American Cancer Society, B-cell lymphomas account for approximately 85% of all lymphomas in the U.S. Diffuse large B-cell lymphoma is the most common, with nearly 30,000 people across the country newly diagnosed each year. Axi-cel was approved by the Food and Drug Administration in 2017 for the treatment of specific patients with B-cell lymphomas, and ongoing studies continue to evaluate the benefits of this therapy relative to current standard approaches.
The international ZUMA-7 trial included 359 patients who were refractory or relapsed within one year of completing first-line therapy. Patients were randomized to receive either axi-cel, an autologous anti-CD19 CAR T cell therapy, or standard of care, which consists of two to three cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation in responding patients.
Patients receiving axi-cel achieved a median progression-free survival (PFS) of 14.7 months versus 3.7 months with standard therapy, with an estimated four-year PFS rate of 41.8% versus 24.4% with standard therapy. The OS and PFS benefits favoring axi-cel were consistent across all key patient subgroups.
The safety of axi-cel was manageable and consistent with previous trials. In those treated with axi-cel, grade 3 cytokine release syndrome occurred in 6% of patients and grade 3 or higher neurologic events occurred in 21% of patients, as reported in the primary event-free survival analysis. No new cytokine release syndrome events were recorded.
“On this groundbreaking trial, more patients lived longer with axi-cel compared to the standard treatment. This is the first trial in any cancer type where a CAR T cell therapy improved survival versus older chemotherapy. This is an incredible breakthrough, but we continue to work to learn where else CAR T cell therapy can prove to be superior in treating patients with high-risk B-cell lymphoma,” Westin said. “We currently are enrolling patients in a study in first-line therapy, the ZUMA-23 clinical trial, to evaluate axi-cel compared with chemotherapy.”
The trial was funded by Kite Pharma, a Gilead Company. Westin receives research support and served on the advisory board and as a consultant for Kite Pharma. A full list of co-authors and their disclosures may be found here.
CHICAGO ― The University of Texas MD Anderson Cancer Center’s Research Highlights showcases the latest breakthroughs in cancer care, research and prevention. These advances are made possible through seamless collaboration between MD Anderson’s world-leading clinicians and scientists, bringing discoveries from the lab to the clinic and back.
This special edition features presentations by MD Anderson researchers at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. In addition to these studies, forthcoming press releases will highlight groundbreaking clinical research, including Phase III trial results evaluating luspatercept versus epoetin alfa in transfusion-dependent patients with myelodysplastic syndromes (Abstract 7003), results from a Phase II trial using zanidatamab in pre-treated HER2-amplified biliary tract cancer (Abstract 4009), further insights into erdafitinib for multiple cancers with FGFR alterations (Abstracts 3121, 4504, LBA4619), interim results on the efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors (Abstract LBA3000), and data from a Phase III trial on axicabtagene ciloleucel versus standard of care in large B-cell lymphoma (Abstract LBA107).
More information on all MD Anderson ASCO Annual Meeting content can be found at MDAnderson.org/ASCO.
Ponatinib combined with chemotherapy controls newly diagnosed Philadelphia chromosome-positive ALL (Abstract 398868)
Standard treatment for patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) includes BCR-ABL1 tyrosine kinase inhibitors, like ponatinib and imatinib, in combination with chemotherapy, but eventually the disease progresses due to the emergence of resistance. According to results from the Phase III PhALLCON trial, led by Elias Jabbour, M.D., patients responded better to ponatinib plus reduced intensity chemotherapy compared to imatinib and chemotherapy. The ponatinib regimen yielded significantly higher rates of minimal residual disease (MRD) negativity compared to imatinib, at 34.4% and 16.7%, respectively. In addition, the rate of MRD negativity at the end of induction was 41.6% with ponatinib and 20.5% with imatinib. The trial included 245 randomized patients with a median age of 54 years. Both treatments were well tolerated, and adverse effects were comparable. Jabbour initially presented the findings in the ASCO Plenary Series on Feb. 17 and will present updated results on June 3.
Adagrasib is safe and shows clinical potential for KRAS G12C-mutated solid tumor types (Abstract 425082)
Adagrasib, a KRAS G12C inhibitor, has shown clinical activity in patients with KRAS G12C- mutated non-small cell lung cancer (NSCLC) and colorectal cancer (CRC), but its effects in other solid tumor types harboring this mutation are not known. In the Phase II KRYSTAL-1 study, researchers led by Shubham Pant, M.D., evaluated adagrasib in 64 patients with KRAS G12C-mutated tumors, excluding NSCLC and CRC. Responses were observed in 20 of 57 patients, an objective response rate (ORR) of 35.1%. The median duration of response was 5.3 months, and the median progression-free survival was 7.4 months. Notably, the ORR in patients with pancreatic and biliary tract cancer was 33.3% and 41.7%, respectively. Most patients (96.8%) experienced treatment-related adverse events, with 27% experiencing grade 3 or 4 adverse events, but none led to drug discontinuation. These results were published in the Journal of Clinical Oncology and Pant presented the findings in the ASCO Plenary Series on April 20. He will present updated findings on June 3.
Medicaid expansion is associated with decreased mortality and racial disparities for patients with gastrointestinal cancers (Abstract 6546)
To examine the effectiveness of the 2014 Affordable Care Act Medicaid expansion on reducing racial disparities in gastrointestinal cancer treatment and survival, researchers led by Naveen Manisundaram, M.D., and George Chang, M.D., analyzed data from the National Cancer Database between 2009 and 2019. Their analysis comprised 22,109 Black and 63,943 white patients, including 19,188 with pancreatic cancer, 60,404 with colorectal cancer and 6,460 with stomach cancer. Medicaid expansion was associated with a significant reduction in two-year mortality, with an even greater reduction in mortality for Black patients residing in expansion states compared to non-expansion states. This study highlights the impact of healthcare access in improving existing racial disparities in mortality in gastrointestinal cancers, which remained the same or worsened in non-expansion states. The researchers plan to examine data from other cancer types to determine if Medicaid expansion had a similar effect on survival and care delivery. Manisundaram will present the findings on June 3.
Study supports safety and efficacy of HER2-targeted therapy in patients with HER2-positive metastatic colorectal cancer (Abstract 3501)
In the single-arm DESTINY-CRC01 trial, the HER2-targeted therapy trastuzumab deruxtecan (T-DXd) demonstrated promising antitumor activity in HER2-positive metastatic colorectal cancer (mCRC) refractory compared to standard treatment. In the global DESTINY-CRC02 randomized Phase II trial, researchers led by Kanwal Raghav, M.D., assessed the efficacy and safety of T-DXd in patients with HER2-positive mCRC at two different doses (5.4mg/kg and 6.4mg/kg). The study met its primary endpoint of confirmed objective response rate (cORR), with cORR in 37.8% in 82 patients who received the lower dose and 27.5% in the 40 patients treated with the higher dose. While some patients experienced grade 3 adverse events, overall safety was consistent with the known profiles of T-DXd, favoring the lower dose. The study highlights the safety profile and potential antitumor activity of T-DXd in a HER2-positive subset of mCRC, meriting further investigation. Raghav will present the findings on June 4.
Immuno-chemotherapy may reduce severe side effects faced by larynx cancer patients (Abstract 6008)
Surgery and radiation therapy are effective treatments for larynx squamous cell carcinoma, a cancer of the voice box, but they can cause side effects such as difficulties with swallowing and speech. To explore new treatments that may reduce these risks, researchers led by Renata Ferrarotto, M.D., tested a new combination of immunotherapy and chemotherapy: pembrolizumab, cisplatin and docetaxel. In a Phase II trial with 23 patients, 78.3% showed no sign of disease in a larynx biopsy after four cycles of treatment. The combination demonstrated disease control in all patients. Overall, 47.8% of patients were treated with immuno-chemotherapy alone. The most common treatment-related adverse events were fatigue, anemia, diarrhea and nausea. The results reveal a combination of these three drugs appears to offer a promising alternative for a subset of larynx cancer patients. Researchers continue to analyze functional outcomes. Ferrarotto will present updated trial results on June 5.
Novel immunotherapy combo continues to show improved outcomes in patients with melanoma (Abstract 9502)
Combining two immune checkpoint inhibitors, nivolumab and relatlimab, provides long-term benefits for patients with untreated advanced melanoma, according to two-year follow-up data from the Phase II/III RELATIVITY-047 study. Led by Hussein Tawbi, M.D., Ph.D., this trial previously demonstrated that the combination improved progression-free survival (PFS) compared to nivolumab alone, leading to Food and Drug Administration approval in 2022. The latest results show that the combination therapy not only improved median PFS (10.2 months vs. 4.6 months) but also achieved a higher objective response rate (43.7% vs. 33.7%). The melanoma-specific survival (MSS), which incorporates only disease-related deaths, was higher in the combination arm, but the median has not yet been reached. These findings were consistent across key subgroups (including MSS) and the safety profile remained consistent with previous reports. These results provide further evidence that nivolumab plus relatlimab is a safe and effective treatment for melanoma. Tawbi will present the data June 5.
Novel targeted therapy BLU-945 produces tumor shrinkage in EGFR-mutant lung cancer (Abstract 9011)
Despite the benefits of targeted therapies like osimertinib, many patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC) eventually experience disease progression. To explore new options for these patients, the Phase I/II SYMPHONY study evaluated the safety and efficacy of BLU-945, a novel therapy targeting mutant EGFR, alone or in combination with osimertinib. Led by Yasir Elamin, M.D., the trial found that nearly half of the patients (48%) who received doses of at least 400 mg per day of BLU-945 experienced a reduction in tumor size. Both monotherapy and combination treatments achieved a robust reduction in circulating cancer DNA and, notably, lower doses of BLU-945 were required when given as part of a combination. While the treatments generally were well-tolerated, minor side effects such as fatigue, nausea, and diarrhea were observed. Elamin will present findings from the ongoing study on June 5.
Biomarker analysis reveals consistent benefits of sotorasib in advanced lung cancer (Abstract 9008)
In CodeBreaK 200, the first randomized Phase III trial of a KRAS G12C inhibitor, researchers demonstrated that sotorasib is superior to the chemotherapy drug docetaxel for previously treated KRAS G12C-mutated advanced non-small cell lung cancer. Sotorasib inhibits the activity of the mutant KRAS G12C protein, which is involved in cancer growth and historically has been difficult to target with drugs. An exploratory biomarker analysis led by Ferdinandos Skoulidis, M.D., Ph.D., found that sotorasib demonstrated consistent clinical benefit in all prespecified subgroups, including patients with co-mutations in key genes STK11, KEAP1, EGFR, MET and TP53, and in those with varied PD-L1 expression levels. Although the study did not confirm any predictive biomarkers, it did identify novel concepts that will be used to inform future research. Skoulidis will present the findings on June 6.
ASCO awards and honors
- Hagop Kantarjian, M.D., chair of Leukemia, to receive ASCO’s highest scientific honor, the David A. Karnofsky Memorial Award
- Four MD Anderson faculty to be named Fellows of the American Society of Clinical Oncology:
o Kerin Adelson, M.D., chief quality & value officer
o Abenaa Brewster, M.D., professor of Clinical Cancer Prevention
o Eduardo Bruera, M.D., professor of Palliative, Rehabilitation and Integrative Medicine
o Apostolia Tsimberidou, M.D., Ph.D., professor of Investigational Cancer Therapeutics
In a new study of trastuzumab deruxtecan, a HER2-targeted antibody drug conjugate, researchers observed encouraging responses and long-lasting clinical benefit in several tumor types. These data from an interim analysis of the Phase II DESTINY-PanTumor02 study, led by The University of Texas MD Anderson Cancer Center, were presented today at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.
The treatment achieved an objective response rate (ORR) of 61.3% with a median duration of response (DOR) of 22.1 months in patients with the highest levels of HER2 expression. Across all patients, the ORR was 37.1% with a median DOR of 11.8 months. An ORR of more than 30% was observed in all cancer types except biliary tract (22%) and pancreatic cancers (4%).
“These are really notable results in this heavily pretreated population, especially in the gynecological cancer cohorts and in patients with higher levels of HER2 expression,” Meric-Bernstam said.
Antibody drug conjugates work by utilizing an antibody to target and bind to a specific protein, in this case HER2, and delivering chemotherapy directly to the cell. Trastuzumab deruxtecan is approved for HER2-expressing breast cancer and is the only antibody drug conjugate approved in the U.S. for HER2-positive gastric cancer and HER2-mutant lung cancer. However, HER2 also is expressed in several other tumor types.
This international open-label study was designed to evaluate the anti-tumor activity of trastuzumab deruxtecan in patients with HER2-expressing locally advanced or metastatic cancers. The trial included 267 patients with cervical, endometrial, ovarian, biliary tract, pancreatic and bladder cancers, as well as other tumors.
The level of HER2 expression was measured by an immunohistochemistry (IHC) test. Seventy-five patients scored IHC 3+, indicating the highest level of HER2 expression, and 125 scored IHC 2+ by central testing. Most patients were female (67%) with an average age of 62 years and a median of two prior lines of therapy. Patients were 61% white, 32.6% Asian and 4.15% other or non-reported ethnicities.
Grade 3 or higher treatment-related adverse events occurred in 38.6% of all patients, the most common being nausea, fatigue and cytopenias. In total, 8.2% of patients discontinued treatment for drug-related adverse events. The safety profile was consistent with previous clinical trials of trastuzumab deruxtecan.
“Our data demonstrate that HER2 expression is actionable in many tumor types. Trastuzumab deruxtecan had compelling clinical activity across tumor types, with prolonged responses and disease stabilization in many patients,” Meric-Bernstam said. “This could help provide a new treatment option for these patients with advanced disease and hard-to-treat HER2-positive cancers who currently have very limited or no options.”
This trial is ongoing, with several patients still receiving treatment. The progression-free survival and overall survival will be analyzed with further follow-up.
This trial is supported by AstraZeneca in collaboration with Daiichi Sankyo. A full list of collaborating authors and disclosures can be found with the abstract here.
Since 1992, the leukemia specialist estimates he’s painted more than 500 canvasses in his spare time. About 50 of those brightly colored, Fauvist-style pieces currently grace the halls of the Leukemia department. He averages about one new painting each week and sometimes gives them away to patients or colleagues.
“I’ll never be a professional artist,” Kantarjian insists. “I’m really not that disciplined about it. I don’t paint unless I feel the urge. But people who are deeply involved in their professions need to have some outlet where they can step outside of their normal roles and just enjoy life. Art and exercise are what take up most of my time outside of MD Anderson.”
The thread connecting art and medicine: innovation
Kantarjian sees a clear thread running between art and medicine.
“In both of those areas,” he notes, “you always want to innovate and create something that did not exist before.”
Kantarjian discovered his own passion for innovation in 1978, when he came to MD Anderson as a medical student from Lebanon.
“Back then, we didn’t really know much about cancer or how to treat it, but I always knew that I wanted to be an oncologist,” he says. “My time at MD Anderson changed my perspective of life completely. Here, I found people to be both innovators and discoverers, whereas my training in Lebanon was all about absorbing knowledge. I wanted to be where the innovators were.”
What gives our leukemia patients hope today
Kantarjian returned to MD Anderson as an oncology fellow in 1981 after finishing medical school and joined the Leukemia faculty in 1983. He became the chair of that department in 1995. And, over the years, he has both seen and been a part of some of the most dramatic advances in the treatment of leukemia.
“In 1981, patients with acute leukemias (ALL, AML) had a cure rate of only 20-30% with intensive chemotherapy. Chronic leukemias (CLL, CML) were not curable, and patients only had about a 20% chance of survival at 10 years post-diagnosis,” he explains. “Now, that figure is well over 90%, and both CML and CLL are functionally curable. And patients with ALL have a 5-year survival rate of 70+%, while patients with AML have 3-to-5-year survival rates above 50-60%.”
Those statistics are just part of what gives hope to today’s leukemia patients — and that’s a feeling Kantarjian is eager to foster.
“If you think about leukemia from a patient’s point of view,” he muses, “a month ago, they were totally normal. Then, they’re suddenly faced with a serious cancer diagnosis. In the 1980s, we didn’t have much to offer them. Now, we do. So, how can you not care and try to do the very best you can for them?”
Why where you go first matters
Even today, Kantarjian notes, some patients don’t respond as well as we’d like to conventional therapies. So, it’s critical to seek care at a place like MD Anderson, where cutting-edge treatments and a robust clinical trials program can keep both our patients and their hopes alive.
“Where you go first really does matter,” he says, “especially when it comes to rare diseases. Leukemias are already very rare, so it’s important to be treated by experts. We have 40 faculty members on staff here who specialize in this disease alone. And they are all driven to offer our patients the best possible treatment at any given time.”
“That’s why, when you look at a list of the top 15 leukemia experts in the world, 10 of them work here at MD Anderson,” he adds. “And that’s why we continue to see improvement year after year in the outcomes of every leukemia we’re treating.”
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Three clinical trials led by researchers at The University of Texas MD Anderson Cancer Center demonstrated positive results from the targeted therapy erdafitinib for patients with multiple tumor types harboring FGFR alterations. The data are being presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.
Erdafitinib is an oral medication that blocks the activity of FGFR signaling proteins, which are important for a variety of normal cellular processes. However, FGFR genetic alterations can drive the development of many cancer types, including urothelial, bile duct, breast, stomach, liver and lung cancers. Erdafitinib was the first approved FGFR-targeted therapy and is the only approved FGFR-targeted option for advanced urothelial cancer.
Erdafitinib demonstrates tumor-agnostic benefits across 16 cancer types (Abstract 3121)
The tumor-agnostic Phase II RAGNAR trial, led by Shubham Pant, M.D., professor of Gastrointestinal Medical Oncology and Investigational Cancer Therapeutics, confirmed the efficacy of erdafitinib in heavily pre-treated patients with advanced FGFR-altered solid tumors across 16 distinct cancer types.
Among 217 patients on the trial, the overall response rate (ORR) was 29.5%, including six complete responses and 58 partial responses. The ORR was comparable across FGFR1-3 mutations and fusions. The treatment achieved a disease control rate of 73.7% and a clinical benefit rate of 45.6%, including an ORR of 56% in patients with pancreatic cancer and 52% in cholangiocarcinoma.
“This study represents the largest tumor-agnostic trial of a targeted therapy to date, and the results demonstrate that erdafitinib provides meaningful clinical benefit in patients with advanced FGFR-altered solid tumors,” Pant said. “These findings suggest erdafitinib may be an important option, regardless of tumor type, for patients with FGFR alternations who have exhausted other available therapies.”
The ongoing open-label, single-arm trial enrolled adult and pediatric patients with FGFR-altered advanced solid tumors, excluding urothelial cancers. All patients had disease progression after at least one prior systemic therapy and had no alternative treatment options.
The median age of participants was 57 years, with a range of 12-79 years, and patients had received a median of two prior lines of therapy. The study included patients with central nervous system tumors, gastrointestinal cancers, gynecologic cancers, lung cancers and other rare tumors.
All but one patient experienced treatment-emergent side effects, and 70% of participants experienced grade 3 or higher adverse events. The safety profile was consistent with the known side effects seen in previous trials.
The trial was supported by Janssen Research & Development, LLC. A complete list of collaborating authors and disclosures can be found with the abstract here.
Adding immunotherapy to erdafitinib elevates response rates in advanced urinary tract cancers (Abstract 4504)
The Phase II NORSE study, led by Arlene Siefker-Radtke, M.D., professor of Genitourinary Medical Oncology, demonstrated clinically meaningful improvements when adding the immunotherapy cetrelimab to erdafitinib for patients with FGFR-altered metastatic urothelial, or urinary tract, cancers.
The combination of erdafitinib with cetrelimab, an anti-PD-1 immune checkpoint inhibitor, achieved an ORR of 54.5% across 44 patients, with six complete responses (CRs) and an overall survival (OS) rate of 68% at 12 months. In comparison, erdafitinib alone achieved an ORR of 44.2% in 43 patients, including one CR and a 12-month OS rate of 56%.
“FGFR-altered tumors typically are immunologically cold and have limited responses to immunotherapy. The goal of this trial was to determine if combining immunotherapy and FGFR-targeted therapy could improve response rates,” Siefker-Radtke said. “We are encouraged by the promising responses and median survival results, and we look forward to future studies to learn the full impact for our patients.”
Standard therapy for patients with advanced urothelial cancer is cisplatin-based chemotherapy, but this regimen has significant side effects and cannot be tolerated by all patients. This open-label study was designed to evaluate the safety and efficacy of erdafitinib plus cetrelimab versus erdafitinib alone in adult patients who had received prior systemic therapy and were ineligible for cisplatin-based therapies.
As of the data cutoff, the trial randomized 87 patients across the treatment arms. Median ages were 69 and 72 on the combination and monotherapy arms, respectively. The median follow-up time was 14.2 months.
The combination presented a safety profile consistent with that of erdafitinib and cetrelimab alone. Grade 3 treatment-related adverse events occurred in 45.5% of patients receiving the combination treatment and 46.5% of patients receiving erdafitinib alone. There was one cetrelimab-related patient death in the combination arm that occurred secondary to pulmonary failure.
The trial was supported by Janssen Research & Development, LLC. A complete list of collaborating authors and disclosures can be found with the abstract here.
Erdafitinib significantly improves patient outcomes over chemotherapy in FGFR-altered urinary tract cancers (Abstract LBA4619)
According to results from cohort one of the Phase III THOR trial, erdafitinib significantly improved survival and response outcomes relative to standard chemotherapy for patients with advanced or metastatic urothelial cancers with FGFR alterations.
With 266 patients randomized to receive either erdafitinib or chemotherapy, the median OS was 12.1 and 7.8 months, respectively, corresponding to a 36% lower risk of death for those treated with erdafitinib. Further, erdafitinib achieved a median progression-free survival of 5.6 months compared to just 2.7 months for chemotherapy. Nearly half (46%) of patients treated with erdafitinib saw their tumors shrink, while just 12% on the chemotherapy arm had an objective response.
“These results demonstrate improved responses and survival outcomes for patients receiving erdafitinib compared to standard-of-care chemotherapy, confirming the benefit for these patients,” said Siefker-Radtke, senior investigator on the trial. “This highlights the significance of a targeted therapy option for patients with FGFR-altered urothelial cancer and is the first biomarker-targeted therapy for this disease.”
Erdafitinib was approved in 2019 by the Food and Drug Administration for advanced FGFR-altered urothelial cancer based on results of a Phase II trial led by Siefker-Radtke. The current trial reinforces the benefits over standard therapeutic options for these patients.
The trial enrolled adults with advanced/metastatic urothelial cancer harboring specific FGFR alterations. All patients had experienced progression after two or fewer prior lines of therapy, including chemotherapy and immunotherapy. Patients were randomized to receive erdafitinib (136) or the investigator’s choice of chemotherapy (130). The patients' median age was 67.
Cohort one of the trial met its primary endpoint of improved OS and was concluded based on achieving predefined superiority criteria. The side effects of the treatment were consistent with the known safety profile of erdafitinib.
The trial was supported by Janssen Research & Development, LLC. A complete list of collaborating authors and disclosures can be found with the abstract here.
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