AACR Annual Meeting 2023

The AACR Annual Meeting is the critical driver of progress against cancer, the place where scientists, clinicians, other health care professionals, survivors, patients, and advocates gather to share and discuss the latest breakthroughs. In April, more than 21,700 attendees from 87 countries gathered in Orlando to communicate, collaborate, and engage with the full spectrum of cancer research.

HIGH-IMPACT CLINICAL TRIALS

The Annual Meeting’s reputation as a presentation venue for practice-changing clinical trials was bolstered in 2023, as a record number of trial abstracts were submitted by the clinical research community. Through the leadership of the AACR Annual Meeting Clinical Trials Committee—led by cochairs Timothy Yap, MBBS, PhD, and Shivaani Kummar, MD—more than 240 trials were presented during the meeting, including 35 oral presentations in plenary sessions and minisymposia. The clinical plenary sessions that showcased these trials spanned a wide range of topics, including Harnessing the Immune System in the Clinic, Hope for Rare Cancers: Novel Targeted and Immunotherapy Agents, Promising Novel Antitumor Strategies in Early Phase Clinical Trials, and Novel Biomarker-driven Molecularly Targeted Therapy Trials. These presentations highlighted critical advances in cancer care across a range of treatment options and cancer types:

KEYNOTE-942 Trial: Personalized mRNA Cancer Vaccine Plus Immunotherapy for High-risk Melanoma. Attempts to design a cancer vaccine that primes patients’ immune systems to destroy tumors have met challenges with regard to potency and specificity. However, advances in high-throughput sequencing and computational methods have enabled researchers to identify cancer-specific neoantigens from individual patients’ tumors.
Jeffrey Weber, MD, PhD, presented the results of KEYNOTE-942, in which researchers developed personalized mRNA vaccines for patients with melanoma that had been surgically removed but had a high risk of recurrence. Patients received the immune checkpoint inhibitor pembrolizumab either alone or in combination with the vaccine, mRNA-4157/V940. This mRNA-based personalized cancer vaccine encodes up to 34 patient-specific tumor neoantigens. Patients in the vaccine arm had a relapse-free survival rate of 78.6% after 18 months, compared with 62.2% in the pembrolizumab arm. This improvement in relapse-free survival was observed both in patients with high and low tumor mutation burden, a common predictor of response to immunotherapy.

Timothy Yap, MBBS, PhD, and Shivaani Kummar, MD

KEYNOTE-942 Trial: Personalized mRNA Cancer Vaccine Plus Immunotherapy for High-risk Melanoma. Attempts to design a cancer vaccine that primes patients’ immune systems to destroy tumors have met challenges with regard to potency and specificity. However, advances in high-throughput sequencing and computational methods have enabled researchers to identify cancer-specific neoantigens from individual patients’ tumors.
Jeffrey Weber, MD, PhD, presented the results of KEYNOTE-942, in which researchers developed personalized mRNA vaccines for patients with melanoma that had been surgically removed but had a high risk of recurrence. Patients received the immune checkpoint inhibitor pembrolizumab either alone or in combination with the vaccine, mRNA-4157/V940. This mRNA-based personalized cancer vaccine encodes up to 34 patient-specific tumor neoantigens. Patients in the vaccine arm had a relapse-free survival rate of 78.6% after 18 months, compared with 62.2% in the pembrolizumab arm. This improvement in relapse-free survival was observed both in patients with high and low tumor mutation burden, a common predictor of response to immunotherapy.

IMbrave050 Trial: Adjuvant Combination Therapy Improves Recurrence-Free Survival for Liver Cancer Patients. In 2020, based on data from a prior phase III trial (IMbrave150) demonstrating that a combination of the immune checkpoint inhibitor atezolizumab and the angiogenesis inhibitor bevacizumab improved outcomes for patients with unresectable hepatocellular cancer (HCC) when given as first-line treatment as compared with compared with sorafenib, the FDA approved that combination as a standard of care. However, the rate of disease recurrence in patients with early-stage HCC following these standard-of-care treatments is typically higher because of the absence of an established adjuvant treatment regimen.
At the AACR Annual Meeting 2023, Pierce Chow, PhD, FRCS(E), presented the results of IMbrave050, a global, multicenter, open-label, randomized phase III clinical trial that investigated whether the atezolizumab-bevacizumab combination given as adjuvant therapy for patients with resectable HCC could delay or prevent recurrence, compared with active surveillance, the current standard of care after complete surgical resection or ablation for this patient population. Dr. Chow reported that the trial met its primary endpoint: after a median follow-up of 17.4 months, patients in the combination treatment arm had a 28% reduction in the risk of recurrence compared with those in the active surveillance arm, a benefit observed across all clinical subgroups.

KEYNOTE-966 Trial: Pembrolizumab-Chemotherapy Combination for Biliary Tract Cancer. Biliary tract cancers are a group of rare and aggressive cancers that arise from the bile ducts and gall bladder. The incidence of these cancers—which typically have a poor prognosis—has been increasing in recent years. The tumor microenvironment of biliary tract cancers inhibits the effectiveness of ICI monotherapies; however, chemotherapies can modulate the immune system, indicating that a combination of ICI and chemotherapy could benefit patients. Data from an earlier phase III trial (TOPAZ-1) led the FDA to approve one such combination (durvalumab and standard-of-care chemotherapies) in 2022.
R. Kate Kelley, MD, presented the results of KEYNOTE-966, a global, multicenter, randomized, double-blind, phase III trial, which compared a combination of the ICI pembrolizumab and current standard-of-care chemotherapeutics gemcitabine and cisplatin with placebo plus gemcitabine and cisplatin as first-line therapy in patients with advanced and/or unresectable biliary tract cancers. Trial data showed that patients in the pembrolizumab arm had a median overall survival of 12.7 months, compared with 10.9 months for those in the placebo arm, and benefit was seen across all subgroups. Dr. Kelley noted that because the KEYNOTE study included more patients than the TOPAZ trial (1,069 versus 685), and because the study population included a higher proportion of patients from western and non-Asian sites, the KEYNOTE results may be more applicable to a global population. Taken together, the results of both trials indicate that ICI-chemotherapy combinations are viable treatment options for these challenging cancers.
AEGEAN Trial: Perioperative Durvalumab-Based Treatment for Patients with Resectable Lung Cancer. Building upon recent FDA approvals of ICI therapies given either before or after surgery, the AEGEAN trial is a global, multicenter, phase III, double-blind, placebo-controlled randomized clinical trial testing the PD-L1-targeted ICI durvalumab given both before and after surgery in patients with resectable non-small cell lung cancer (NSCLC).
John V. Heymach, MD, PhD, presented interim results of the trial at the Annual Meeting, noting that the final analysis showed a pathological complete response of 17.2% in the treatment arm, versus 4.3% in the placebo arm. In addition, these results showed that patients in the durvalumab-based regimen arm had a 32% reduction in the risk of disease progression precluding definitive surgery, disease recurrence, or death compared with those in the chemotherapy alone arm. The results indicate that PD-L1-targeted durvalumab as perioperative therapy can be considered a new standard of care for NSCLC patients.

KEYNOTE-966 Trial: Pembrolizumab-Chemotherapy Combination for Biliary Tract Cancer. Biliary tract cancers are a group of rare and aggressive cancers that arise from the bile ducts and gall bladder. The incidence of these cancers—which typically have a poor prognosis—has been increasing in recent years. The tumor microenvironment of biliary tract cancers inhibits the effectiveness of ICI monotherapies; however, chemotherapies can modulate the immune system, indicating that a combination of ICI and chemotherapy could benefit patients. Data from an earlier phase III trial (TOPAZ-1) led the FDA to approve one such combination (durvalumab and standard-of-care chemotherapies) in 2022.
R. Kate Kelley, MD, presented the results of KEYNOTE-966, a global, multicenter, randomized, double-blind, phase III trial, which compared a combination of the ICI pembrolizumab and current standard-of-care chemotherapeutics gemcitabine and cisplatin with placebo plus gemcitabine and cisplatin as first-line therapy in patients with advanced and/or unresectable biliary tract cancers. Trial data showed that patients in the pembrolizumab arm had a median overall survival of 12.7 months, compared with 10.9 months for those in the placebo arm, and benefit was seen across all subgroups. Dr. Kelley noted that because the KEYNOTE study included more patients than the TOPAZ trial (1,069 versus 685), and because the study population included a higher proportion of patients from western and non-Asian sites, the KEYNOTE results may be more applicable to a global population. Taken together, the results of both trials indicate that ICI-chemotherapy combinations are viable treatment options for these challenging cancers.
AEGEAN Trial: Perioperative Durvalumab-Based Treatment for Patients with Resectable Lung Cancer. Building upon recent FDA approvals of ICI therapies given either before or after surgery, the AEGEAN trial is a global, multicenter, phase III, double-blind, placebo-controlled randomized clinical trial testing the PD-L1-targeted ICI durvalumab given both before and after surgery in patients with resectable non-small cell lung cancer (NSCLC).
John V. Heymach, MD, PhD, presented interim results of the trial at the Annual Meeting, noting that the final analysis showed a pathological complete response of 17.2% in the treatment arm, versus 4.3% in the placebo arm. In addition, these results showed that patients in the durvalumab-based regimen arm had a 32% reduction in the risk of disease progression precluding definitive surgery, disease recurrence, or death compared with those in the chemotherapy alone arm. The results indicate that PD-L1-targeted durvalumab as perioperative therapy can be considered a new standard of care for NSCLC patients.

CUTTING-EDGE EDUCATIONAL PROGRAM

Under the leadership of cochairs Carlos M. Caldas, PhD, and Karolina Palucka, MD, PhD, the AACR Education Committee developed a comprehensive educational program for the Annual Meeting, organizing more than 70 educational sessions and methods workshops.

Topics included clinical trial design to support diversity in patient enrollment; novel technologies for early cancer detection; liquid biopsies for early detection and monitoring; and emerging methods to target protein degradation.

INSPIRING PLENARY SESSIONS

Following the two-day educational program, each of the four days of the Annual Meeting's main scientific program featured a leading-edge plenary session—beginning with the Opening Plenary Session titled "Advancing the Frontiers of Cancer Science and Medicine." Moderated by Annual Meeting Program Chair Robert H. Vonderheide, MD, DPhil, the session addressed a range of topics, including discoveries in tumor immunology, cancer cachexia, malignancies in people with HIV, and centering equity at the frontiers of cancer care.

Additional plenary sessions addressed compelling topics such as Early Detection and Interception of Cancer, Embracing Immune Ecosystems, and New Concepts in Drug Discovery and Engineering.

AACR Annual Meeting 2023 Program Chair Robert H. Vonderheide, MD, DPhil

Additional plenary sessions addressed compelling topics such as Early Detection and Interception of Cancer, Embracing Immune Ecosystems, and New Concepts in Drug Discovery and Engineering.

PRESIDENTIAL SELECT SYMPOSIUM: PREGNANCY AND CANCER

A cancer diagnosis during pregnancy, or a pregnancy occurring in a patient receiving anticancer therapy, can pose complex challenges for patients and their care teams. AACR President (2022–2023) Lisa M. Coussens, PhD, FAACR, highlighted situations in which the goals of patient-centered, ethical cancer care are impacted by pregnancy in her Presidential Select Symposium at the Annual Meeting.

In presentations and a panel discussion, Ann H. Partridge, MD, MPH, Virginia F. Borges, MD, Brandon M. Hayes-Lattin, MD, and patient advocate Julia Maues addressed the evidence that informs the care of pregnant cancer patients—including the critical gaps in knowledge with regard to the risks of treatment to a pregnant patient and fetus, particularly as new therapies and treatment modalities are introduced.

Ann Partridge, MD, MPH, presents in the Presidential Select Symposium at the AACR Annual Meeting 2023

AACR Annual Meeting 2023

Advancing the Frontiers of Cancer Science and Medicine

HIGH-IMPACT CLINICAL TRIALS

CUTTING-EDGE EDUCATIONAL PROGRAM

INSPIRING PLENARY SESSIONS

PRESIDENTIAL SELECT SYMPOSIUM: PREGNANCY AND CANCER

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