ESMO 2024 Annual Congress: Preview of Key Late-Breaking Abstracts
In this preview, we highlight the key late-breaking abstracts to be presented at the 2024 ESMO Congress across various tumor types that may impact clinical practice.
DNA helix enlarged model in bright colors and spots: © Radomir Jovanovic - stock.adobe.com
With the 2024 European Society for Medical Oncology (ESMO) Congress quickly approaching, anticipation is building around the latest advancements in oncology. Late-breaking abstracts highlight the most transformative and highly relevant advancements that offer potential changes to treatment paradigms.
“We look forward to a lot of data coming that has not been released. With ESMO coming up, we are very excited,” said Alex Spira, MD, PhD, FACP, thoracic oncologist at Virginia Cancer Specialists, in an interview with Targeted OncologyTM.
Here, we highlight the key late-breaking abstracts across various tumor types that may impact clinical practice.
Breast Cancer
LBA18: Trastuzumab Deruxtecan in HER2+ Advanced/Metastatic Breast Cancer
Investigators on the DESTINY-Breast-12 trial (NCT04739761) will present primary results for fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) in HER2-positive (HER2+) advanced or metastatic breast cancer, including patients with or without brain metastases.1
In the open-label, multicenter, international, phase 3b/4 study, the efficacy and safety of T-DXd is being evaluated when given to patients at a dose of 5.4 mg/kg every 3 weeks. Those enrolled must have previously treated HER2+ breast cancer that has progressed following 1 or more prior anti-HER2–based regimens. Patients must also have been given up to 2 lines of therapy in the metastatic setting.
The primary end points of the study include overall response rate (ORR) in cohort 1 and progression-free survival (PFS) in cohort 2. In both cohorts, secondary end points include overall survival (OS), duration of response (DOR), time to progression, duration of subsequent therapy, PFS2, safety, and changes in symptoms, functioning, and quality of life.
This study could offer new hope for patients with HER2+ disease, demonstrating enhanced efficacy and safety profiles.
LBA19: Capivasertib Plus Paclitaxel in Metastatic Triple-Negative Breast Cancer (mTNBC)
The phase 3 CAPItello-290 trial (NCT03997123) is evaluating capivasertib (Truqap) combined with paclitaxel as a first-line treatment for patients with locally advanced or metastatic triple-negative breast cancer (TNBC).2
In June 2024, findings from the study showed that the combination failed to meet its dual primary end points of improved OS compared with paclitaxel plus placebo in both the overall trial population of patients with locally advanced or metastatic TNBC and in a subgroup of patients with tumors harboring PIK3CA, AKT1, or PTEN alterations. The safety profile of capivasertib plus paclitaxel was similar in this study compared with that of each agent alone, and no new safety signals were identified.
3D rendering of breast cancer: © Giovanni Cancemi - stock.adobe.com
LBA21: HER2-Low and HER2-Ultralow Status Determination in Metastatic Breast Cancer
The DESTINY-Breast06 study (NCT04494425) is evaluating HER2-low and HER2-ultralow status in hormone receptor–positive (HR+) metastatic breast cancer. Data presented as a late-breaking abstract at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting earlier this year showed that T-DXd led to a median PFS of 13.2 months vs 8.1 months with chemotherapy, as assessed by blinded independent central review, in patients with HR+/HER2-low disease. This PFS benefit represented a 38% reduction in the risk of disease progression or death (HR, 0.62; 95% CI, 0.51-0.74; P <.0001).3
In the HER2-ultralow disease patient population, there was a 22% (HR, 0.78; 95% CI, 0.50-1.21) reduction in the risk of disease progression or death with T-DXd, and the median PFS was 13.2 months in the combination arm vs 8.3 months with chemotherapy.
“There is a trend for positive overall survival with the landmark analysis of 1 year. Patients alive are 81% in the chemotherapy arm vs 87% in the T-DXd arm,” Giuseppe Curigliano, MD, PhD, professor of medical oncology at the University of Milan, head of the division of early drug development at the European Institute of Oncology, and principal investigator for the trial, previously shared with Targeted OncologyTM.
LBA23: Abemaciclib Plus Endocrine Therapy with or Without Induction Paclitaxel
In the ABIGAIL study (NCT04603183), experts are assessing the combination of abemaciclib (Verzenio) with endocrine therapy, with or without a short course of paclitaxel, in HR+/HER2-negative advanced breast cancer.4
The primary end point of the multicenter, randomized, open-label, phase 2 trial is 12-week ORR as per RECIST v1.1, and key secondary end points include ORR, clinical benefit rate, 12-week PFS, time to response, DOR, OS, time to first subsequent therapy, time to second subsequent therapy, time to first chemotherapy for patients in the abemaciclib plus endocrine therapy arm, patient-reported outcomes, and safety as per NCI-CTCAE 5.0.4
These will be the first results of the trial to be published.
Gastrointestinal Cancer
Gastric cancer cells: © LASZLO - stock.adobe.com
LBA39: Adjuvant Atezolizumab/Bevacizumab in High-Risk Hepatocellular Carcinoma
Updated data from the IMbrave050 trial (NCT03434379) of adjuvant atezolizumab (Tecentriq) plus bevacizumab (Avastin) vs active surveillance in resected or ablated high-risk hepatocellular carcinoma (HCC) will be presented.5 Previous data showed that the primary end point was met, as adjuvant atezolizumab/bevacizumab following surgery improved recurrence-free survival (RFS) vs active surveillance in early-stage HCC at a high risk for recurrence.
In addition to RFS, key secondary end points being evaluated include OS and RFS as determined by the investigator and RFS in patients with PD-L1–positive disease.
The combination of atezolizumab and bevacizumab is approved by the FDA for the treatment of adult patients with unresectable locally advanced or metastatic HCC with no prior systemic treatment. The approval was supported by results from the prior IMbrave150 study (NCT03434379). The combination is now being explored as an adjuvant treatment since resection and ablation are associated with high rates of recurrence. According to Mark Yarchoan, MD, immunotherapy after surgery is hypothesized to be a solution to this problem.
“Adjuvant atezolizumab plus bevacizumab is likely to become a new standard of care for patients with resectable HCC,” added Yarchoan, associate professor of oncology at Johns Hopkins Medicine.
LBA24: Neoadjuvant Immunotherapy in Locally Advanced MMR-Deficient Colon Cancer
The NICHE-2 trial (NCT03026140) is evaluating neoadjuvant immunotherapy in mismatch repair-deficient (dMMR) colon cancer. In the phase 2 study, patients with nonmetastatic, locally advanced, previously untreated dMMR colon cancer are being treated with neoadjuvant nivolumab (Opdivo) plus ipilimumab (Yervoy).6
Experts are assessing 2 primary end points: safety defined by timely surgery and 3-year disease-free survival (DFS). Secondary end points of the trial include pathological response and results of genomic analyses.
With 3-year DFS data, this study may introduce new strategies for managing locally advanced colon cancer.
Lung Cancer
LBA48: Adjuvant Durvalumab in Completely Resected NSCLC
The phase 3 ADJUVANT BR.31 trial (NCT02273375) is assessing adjuvant durvalumab (Imfinzi) in patients with completely resected non–small-cell lung cancer (NSCLC). High-level results from the study, which is sponsored by the Canadian Cancer Trials Group, showed treatment with durvalumab did not achieve statistical significance for the primary end point of DFS compared with placebo in this population, which consisted of patients with early-stage NSCLC following complete tumor resection whose tumors had a PD-L1 expression level of at least 25%.7
The safety profile for durvalumab in this study was consistent with its known safety profile. There were also no new safety signals observed.
Illustration of lungs: © yodiyim - stock.adobe.com
LBA53: Nivolumab Plus Relatlimab With Platinum-Doublet Chemotherapy (PDCT) vs Nivolumab Plus PDCT as First-Line Treatment for Stage IV or Recurrent NSCLC
The RELATIVITY-104 study (NCT04623775) is examining the combination of nivolumab and relatlimab (Opdualag) with platinum doublet chemotherapy (PDCT) vs single-agent nivolumab plus PDCT in patients with stage IV or recurrent NSCLC.8
In the randomized, 2-part, phase 2 study, patients with first-line stage IV or recurrent NSCLC are being enrolled if they are aged 18 years or older with an ECOG performance status of 0 or 1 and no prior treatment with systemic anticancer therapies for advanced disease.
The primary end point in part 1 is to evaluate treatment-related adverse events leading to discontinuation within 12 weeks of the first dose. In part 2, the primary end point is PFS per RECIST v1.1 by blinded independent clinical review. Secondary end points for part 2 also consist of safety and tolerability across biomarker subgroups and ORR.
LBA54: Amivantamab Plus Chemotherapy in EGFR-Mutated Advanced NSCLC: OS Data From MARIPOSA-2
The phase 3 MARIPOSA-2 study (NCT04988295) is comparing amivantamab (Rybrevant) plus chemotherapy to chemotherapy alone in patients with EGFR-mutated advanced NSCLC. Prior data from the MARIPOSA-2 study showed that amivantamab with chemotherapy administered with or without lazertinib (Lazcluze) led to a statistically significant and clinically meaningful improvement in PFS among patients with locally advanced or metastatic EGFR exon 19 deletion or L858R substitution NSCLC, meeting the primary end point of the study.9
At the ESMO Congress, researchers are sharing OS data from the second interim analysis of MARIPOSA-2.
“In MARIPOSA-2, initially, we had significant data showing that PFS was better. I think we are going to see this year, hopefully, the updated overall survival data and longer PFS data to solidify its use,” explained Spira. “We look forward to that data coming and we are excited.”
With this interim analysis, new treatment options for patients who progress on osimertinib (Tagrisso) could be in sight.
LBA57: Adagrasib vs Docetaxel in KRAS G12C-Mutated Advanced NSCLC
Experts on the KRYSTAL-12 trial (NCT04685135) are evaluating adagrasib (Krazati) vs docetaxel in patients with KRAS G12C-mutated advanced NSCLC and brain metastases.10 The study sought to build on findings from the phase 1/2 KRYSTAL-1 trial (NCT03785249) which revealed that adagrasib demonstrated deep, durable responses in patients with previously treated KRAS G12C-mutated NSCLC. Experts are also looking to compare adagrasib with docetaxel in this intent-to-treat population.
“I think the biggest takeaway is that this phase 3 KRYSTAL-12 study now confirms this standard of care in the second-line setting for patients that have non–small cell lung cancer that harbors this KRAS G12C mutation. Adagrasib has become a standard of care for medical oncologists and providers taking care of patients that have this mutation in the second-line setting,” said Robert Jotte, MD, PhD, medical oncologist/hematologist at Rocky Mountain Cancer Centers, in an interview with Targeted OncologyTM on the KRYSTAL-12 study.
Conceptual image for viral etiology of prostate cancer: © Dr_Microbe - stock.adobe.com
Genitourinary Cancer
LBA73: Tivozanib and Nivolumab vs Tivozanib Monotherapy in RCC
The phase 3 TiNivo-2 study (NCT04987203) is comparing tivozanib (Fotivda) plus nivolumab vs tivozanib monotherapy in patients with renal cell carcinoma (RCC) who have received 1 or 2 prior therapies.11
In July 2024, data from the study were reported showing that nivolumab added to 0.89 mg of tivozanib failed to increase PFS in patients with advanced metastatic RCC whose tumors had progressed following prior immune checkpoint inhibitors. This failed to meet the primary end point of the phase 3 study.
“Longer follow-up from…ongoing trials such as TiNivo-2 will be helpful to determine the role of maintenance [immunotherapy],” Bradley McGregor, MD, genitourinary oncologist at Dana-Farber Cancer Institute, previously told Targeted OncologyTM.
LBA68: Darolutamide Plus Androgen-Deprivation Therapy in mHSPC
Investigators on the ARANOTE trial (NCT04736199) are assessing darolutamide (Nubeqa) plus androgen deprivation therapy (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC). The findings may lead to changes in first-line treatment approaches.
The primary end point of the phase 3 ARANOTE trial was met in July 2024 as darolutamide plus ADT led to improvements in radiological PFS in patients with mHSPC.12
“The positive results from the ARANOTE trial reinforce the role of darolutamide as a treatment option for patients with metastatic hormone-sensitive prostate cancer, which represents about 15% of annual prostate cancer incidence in the US,” Neal Shore, MD, FACS, medical director, Carolina Urologic Research Center, told Targeted OncologyTM prior to the ESMO Congress. “These data demonstrate the potential of this therapy to provide significant benefits to patients with mHSPC, regardless of chemotherapy use.”
Concept of gynecologic cancer: © tom - stock.adobe.com
Gynecologic Cancer
LBA33: Olaparib/Cediranib Maintenance Therapy in Platinum-Sensitive Ovarian Cancer
In the ICON9 trial (NCT03278717) maintenance therapy with olaparib (Lynparza) and cediranib is being compared with olaparib alone in patients with relapsed platinum-sensitive ovarian cancer.13
In the phase 3, randomized, controlled, international trial, patients who have high-grade serous or endometrioid carcinoma of the ovary, fallopian tube, or peritoneum who are progressing more than 6 months after first-line platinum-based chemotherapy and who have responded to second-line platinum-based chemotherapy will be randomized 1:1 to receive either oral olaparib and cediranib or oral olaparib alone. The primary end points of the trial are PFS and OS.
LBA29: Final OS Results From PRIMA/ENGOT-OV26/GOG-3012
Final OS data from the PRIMA/ENGOT-OV26/GOG-3012 trial (NCT02655016) are being presented at the meeting. The study is evaluating niraparib (Zejula) as primary maintenance therapy for the treatment of patients with newly diagnosed advanced ovarian cancer.14
“The PRIMA/ENGOT-OV26/GOG-3012 study was the first to expand access to PARP inhibitors in patients who [either] had or did not have BRCA mutations,” Leslie M. Randall, MD, MAS, professor and director of gynecologic oncology at Virginia Commonwealth University, said during a Targeted Oncology™ Case-Based Roundtable™ event. “They enrolled patients with newly diagnosed advanced ovarian cancer at high risk for recurrence after response to first-line platinum-based chemotherapy. That meant…they either had neoadjuvant chemotherapy and had a complete or partial response or had residual disease after frontline surgery.”
Melanoma
LBA42: Distant Metastasis-Free Survival of Neoadjuvant Nivolumab/Ipilimumab
The NADINA trial (NCT04949113) is comparing neoadjuvant nivolumab plus ipilimumab to adjuvant nivolumab in resectable macroscopic stage III melanoma.15 Previously reported results showed that a total of 423 patients underwent randomization and at a median follow-up of 9.9 months, the estimated 12-month event-free survival was 83.7% (99.9% CI, 73.8%-94.8%) among patients in the neoadjuvant group vs 57.2% (99.9% CI, 45.1%-72.7%) in the adjuvant group. Eight months was the difference in restricted mean survival time was (99.9% CI, 4.94-11.05; P <.001), with a hazard ratio for progression, recurrence, or death of 0.32 (99.9% CI, 0.15-0.66).
Of those in the neoadjuvant group, 59.0% of patients had a major pathological response, 8.0% had a partial response, and 26.4% had a nonresponse. Additionally, 2.4% had progression. The estimated 12-month RFS was 95.1% among those in the neoadjuvant group who had a major pathological response, 76.1% among those with a partial response, and 57.0% among those with a nonresponse.
The updated results presented at ESMO may offer new insights into treatment efficacy and patient outcomes.
These are just some of the late-breaking abstracts to be presented at the 2024 ESMO Annual Congress. Each represents key developments that could reshape standard treatments and improve patient outcomes.
