MD Anderson Research Highlights: ASCO 2023 Special Edition
Featuring novel treatments for ALL, CRC, melanoma, EGFR and KRAS mutations, as well as reduced racial disparities in GI cancers
MD Anderson News Release May 25, 2023
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