The annual meeting of the American Association for Cancer Research was held virtually this year from April 27 to 28 and attracted approximately 18,000 participants from around the world, including scientists, cancer survivors, clinicians, allied health professionals, industry professionals, and others interested in cancer research. The conference highlighted recent advances in the treatment, management, and prevention of cancer.
In the SWOG S1320 phase II clinical trial, Alain Algazi, M.D., of the University of California in San Francisco, and colleagues compared the efficacy of continuous and intermittent dosing of dabrafenib (a BRAF inhibitor) and trametinib (a MEK inhibitor) in patients with BRAF-mutated melanoma.
“Laboratory observations previously showed that continued exposure to drugs that shut off a broken growth switch, called BRAF, that causes melanoma to grow could lead to the development of resistant cells that required continued drug exposure for optimal growth. In essence, treatment-resistant tumor cells make more of the broken switch so that they can compensate for the presence of drug,” Algazi said. “We tested this in patients by comparing the period of disease control, or progression-free survival, in patients treated continuously with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib to the period of disease control in patients treated with these drugs on a three-week off, five-week on schedule.”
Contrary to results seen in animal studies, the investigators found that continuous dosing of the drugs led to a longer period of disease control.
“This suggests that the animal findings could not be replicated in patients. This is an important finding because intermittent dosing is being tested in at least five studies in patients with metastatic melanoma and in nearly 70 studies in a variety of cancer types. Our data raise a concern that intermittent dosing may not work using many commonly used anticancer drugs,” Algazi said. “Cancer may be more complicated in people than it is in animals, and the drugs that we use to treat human cancer may act differently in, for example, mice. Although some preclinical studies may provide important advances in patient care, such as studies showing that using two drugs instead of one keeps melanoma patients well for longer, others may not be applicable to a broad patient population without modifying the treatments to account for differences between people and animals.”
Using geographic- and population-specific analyses, Kimlin T. Ashing, Ph.D., of the City of Hope in Duarte, California, and colleagues found that neighborhoods with lower-income and higher-minority populations had a greater number of tobacco/vape shops, increased use of disposable electronic nicotine delivery systems, and lower-priced tobacco products.
“Shops that have the singular focus of tobacco distribution target low socioeconomic communities and communities of color, including lower-income Asian, black, and Latino neighborhoods. Some of the communities that fit this description in our study had two tobacco shops per square mile. Wealthy communities, on the other hand, have taken extra precautions to prevent dedicated tobacco shops from entering their neighborhoods. As a result, the wealthy communities in our study had zero tobacco shops,” Ashing said. “New policies, legislation, and regulations are needed to protect lower socioeconomic communities and communities of color from being targets for shops that solely sell tobacco products.”
One author disclosed financial ties to CHAD Therapeutics.
In the I-SPY 2 trial, Lajos Pusztai, M.D., of the Yale Cancer Center in New Haven, Connecticut, and colleagues found that immune checkpoint inhibitors increase pathologic complete response (pCR) rates when combined with taxane neoadjuvant chemotherapy in stage II to III human epidermal growth factor receptor 2-negative breast cancer.
“The I-SPY 2 trial results also demonstrate that this increase is observed both in triple-negative breast cancer and high molecular risk (i.e., MammaPrint ultra-high) estrogen receptor-positive cancers. To what extent olaparib contributed to the improvement in pCR cannot be teased out from the I-SPY 2 design and requires further studies,” Pusztai said. “Currently, there is no immune checkpoint inhibitor approved as neoadjuvant treatment for breast cancer by the U.S. Food and Drug Administration. Pembrolizumab is expected to be approved in this space based on demonstrating significantly improved pCR rate and a trend to improve recurrence-free survival in preliminary survival analysis in the Keynote 522 trial. There are several ongoing neoadjuvant clinical trials that provide patients access to these drugs.”
Several authors disclosed financial ties to the pharmaceutical industry.
Haneen Shalabi, M.D., of the National Institutes of Health in Bethesda, Maryland, and colleagues found that bispecific CAR T cells are active and well tolerated in pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia.
“In our preliminary data, we found that treating patients with bispecific CAR T cells (those that simultaneously target CD19 and CD22 antigens) appeared to be safe, well tolerated, and active in pediatric and young adult patients. The best responses to this treatment were observed among patients who had not previously received CAR T-cell therapy,” Shalabi said. “While this approach appeared to be effective in treating patients with disease in the bone marrow, we found that CAR T cells have had a mixed response in extramedullary sites of disease. Through this study, we were pleased to demonstrate that it is feasible to manufacture bispecific, bivalent CAR T cells.”
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