ASCO in Review: Oncologists See Practice-Changing, Affirming Data

2023-06-08

临床结果临床2期疫苗上市批准ASCO会议

Pictured: A cancer outbreak/iStock, wildpixel The 2023 American Society of Clinical Oncology (ASCO) meeting had implications for patients, physicians and biopharma companies. AstraZeneca’s Tagrisso (osimertinib) demonstrated its worth in EGFR-mutated non-small cell lung cancer, Novartis’ Kisqali impressed oncologists in early breast cancer, Merck’s Keytruda outpaced Astra’s Imfinzi in the perioperative NSCLC setting, and Moderna and Merck released more promising results for their personalized cancer vaccine. Practice-Changing/Affirming Data During the plenary session on June 4, AstraZeneca presented an analysis of overall survival data from the ADAURA trial of adjuvant Tagrisso in resected epidermal growth factor receptor-mutated (EGFRm) stage IB–IIIA NSCLC epidermal growth factor receptor-mutated (EGFRm) stage IB–IIIA NSCLC. Tagrisso reduced the risk of death in both the primary analysis and overall trial populations by 51% compared to the placebo. Moreover, 88% of Tagrisso-treated patients were alive after five years compared to 78% of placebo recipients. Elaine Shum, a medical oncologist at NYU Langone Health’s Perlmutter Cancer Center and assistant professor of medicine at NYU Grossman School of Medicine who consults for and advises AstraZeneca, called the data “practice affirming” as she said many oncologists had been using adjuvant Tagrisso since 2020 when the company first reported survival results from Tagrisso. “I think an overall survival benefit really has not been seen with targeted therapies in the space before,” Shum told BioSpace. “To see this now . . . was really amazing, to be quite honest.” Xiuning Le Xiuning Le, a thoracic medical oncologist at the University of Texas MD Anderson Cancer Center Cancer Center, echoed Shum, telling BioSpace the data is “practice confirming.” “The significant survival benefit for taking osimertinib strongly argues that we need to do better to test for EGFR mutations in surgically resected lung cancers so that we do not miss the benefit for our patients,” said Le, who receives consulting and/or advisory fees from AstraZeneca and Merck, among other biopharma companies. For AstraZeneca AstraZeneca, these results could add dollars to Tagrisso’s already impressive haul. Tagrisso brought in $5.3 billion for AstraZeneca AstraZeneca in 2022, which came mostly from the metastatic disease setting, but the latest results could boost sales by $1.8 billion, SVB analyst Andrew Berens told STAT News. Pavani Chalasani, director of the Division of Hematology and Oncology at the George Washington Cancer Center Cancer Center, told BioSpace results from the NATALEE trial of Novartis’s Kisqali in adjuvant HR+/HER2- early breast cancer HR+/HER2- early breast cancer “will likely be practice-changing.” The data, announced June 2, showed that adding Kisqali to a hormonal therapy reduced patients’ risk for recurrence by 25% compared to those on the endocrine therapy alone. Kisqali is currently approved to treat advanced and metastatic breast cancer and Novartis intends to submit for approval by the end of 2023. “If the results continue to show benefit at an update, it will be approved and a huge win for patients,” Chalasani said. Keytruda Bests Imfinzi in Perioperative NSCLC Arguably the most-anticipated Keytruda data at ASCO also came in NSCLC, as the PD-1/PD-L1 inhibitor PD-1/PD-L1 inhibitor topped Imfinzi in treating patients with resectable stage II, IIIA or IIIB disease when given both prior to and after surgery. After 25 months, perioperative treatment with Keytruda plus chemotherapy in the KEYNOTE-671 study reduced the risk of disease recurrence, progression or death by 42% compared to pre-operative chemotherapy, according to a press release issued June 3 by Merck. “The overall survival data await maturation but show a good trend,” Le said, adding that more research is needed to determine which patients will benefit more from treatment with Keytruda after surgery. Shum said that while the results add to advancements in the space, “right now, I don’t know that it is a clear answer as to how we should approach patients.” As the data from different studies can’t be directly compared, she said there are still questions as to the best way to sequence the treatment regimen. A ‘Different Approach’ to a Cancer Vaccine On June 5, Moderna and Merck presented data from a Phase IIb study showing that their personalized cancer vaccine mRNA-4157 in combination with Keytruda reduced the risk of spread to other organs or death in high-risk melanoma by 65%. The data followed an American Association for Cancer Research meeting presentation that showed the combo reduced the risk of cancer recurrence or death by 44% compared to Keytruda alone. Lynn Schuchter Incoming ASCO President Lynn Schuchter, director of the Tara Miller Melanoma Center at Penn Medicine, told BioSpace that oncologists have been searching for a melanoma vaccine strategy for 30 years, but “all of the prior clinical trials have failed.” The mRNA cancer vaccine “is [a] totally different way of thinking about how a vaccine strategy could work,” she said. “It’s a unique way to stimulate the immune system in a very specific way. . . . I think the strategy of combining this kind of approach with PD-1 antibodies is going to be highly effective.” Merck and Moderna are gearing up for a Phase III trial in melanoma later in 2023, according to a June 5 press release. Penn will be one of the trial sites, and Schuchter said she believes the study will enroll patients “very, very rapidly.” At a conference Penn held for melanoma patients in May, “I cannot tell you how many patients asked us about the mRNA vaccine for melanoma,” Schuchter said. “The really tantalizing results from the Phase II study got the melanoma patient community so excited, and they’re eager to participate in the clinical trials.” De-Escalation Finally, Schuchter said the concept of de-escalation and “less is more” was an important area of research on display at ASCO. To illustrate her point, she cited the PROSPECT trial, which showed that radiation therapy prior to surgery was unnecessary for a group of rectal cancer patients. Specifically, the study showed that chemotherapy with fluorouracil, leucovorin and oxaliplatin prior to surgery was non-inferior to chemoradiotherapy for disease-free survival. Pelvic radiation can be very toxic in terms of both acute and long-term consequences, Schuchter said, “and it was just such an important study to show that we didn’t need to use radiation therapy and that you can get the exact same local control.” Schuchter assumed the president’s gavel at the end of May. When her term comes to an end, coinciding with ASCO 2024, she said she hopes to see robust educational sessions and scientific abstracts on the role of artificial intelligence in drug development, care and delivery and imaging. This year, she said she was struck to see the international participation and energy of young faculty and clinicians after a break for the COVID-19 pandemic. “It’s clear that people are so hungry to be in person to experience this.” Heather McKenzie is a senior editor at BioSpace, focusing on neuroscience, oncology and gene therapy. You can reach her at heather.mckenzie@biospace.com. Follow her on LinkedIn and Twitter @chicat08.