ESMO 2024 Annual Congress: Preview of Key Late-Breaking Abstracts

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 Oncology^TM.

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 Oncology^TM.

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 Oncology^TM 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 Oncology^TM.

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 Oncology^TM 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.

REFERENCES:

1. Lin NU, Ciruelos E, Jerusalem G, et al. Abstract OT2-16-02: Open-label, phase 3b/4 study of trastuzumab deruxtecan (T-DXd) in patients with or without baseline brain metastasis with advanced/metastatic human epidermal growth factor receptor 2–positive breast cancer: DESTINY-Breast12. Cancer Res. 2023;83(Suppl 5):OT2-16-02. doi:10.1158/1538-7445.SABCS22-OT2-16-02

2. Update on the CAPItello-290 phase III trial for Truqap plus chemotherapy in advanced or metastatic triple-negative breast cancer. News release. AstraZeneca. June 18, 2024. Accessed August 28, 2024. https://tinyurl.com/45z9h3fy

3. ENHERTU® demonstrated a median progression-free survival of 13.2 months in HR positive, HER2 low and HER2 ultralow metastatic breast cancer following one or more lines of endocrine therapy. News release. Daiichi-Sankyo. June 2, 2024. Accessed August 28, 2024. https://tinyurl.com/49bf24bz

4. Llombart-Cussac A, Gligorov J, Di Cosimo S, et al.Abstract OT2-19-06: phase 2 study of abemaciclib in combination with endocrine therapy with or without paclitaxel induction in patients with hormone receptor-positive, HER2-negative advanced breast cancer and aggressive disease criteria: ABIGAIL. 2022;83(Suppl 4): OT2-19-06. doi:10.1158/1538-7445.SABCS21-OT2-19-06

5. Qin S, Chen M, Cheng AL, et al. Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2023;402(10415):1835-1847. doi:10.1016/S0140-6736(23)01796-8

6. Chalabi M, Verschoor YL, Tan PB, et al. Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair-Deficient Colon Cancer. N Engl J Med. 2024;390(21):1949-1958. doi:10.1056/NEJMoa2400634

7. Update on ADJUVANT BR.31 phase III trial of Imfinzi in non–small cell lung cancer. News release. AstraZeneca. June 25, 2024. Accessed September 6, 2024. https://tinyurl.com/36v7mrpy

8. A study of relatlimab plus nivolumab in combination with chemotherapy vs. nivolumab in combination with chemotherapy as first line treatment for participants with stage IV or recurrent non-small cell lung cancer (NSCLC). ClinicalTrials.gov. Updated June 6, 2024. Accessed September 6, 2024. https://clinicaltrials.gov/study/NCT04623775

9. Passaro A, Wang J, Wang Y, et al. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Ann Oncol. 2024;35(1):77-90. doi:10.1016/j.annonc.2023.10.117

10. Bristol Myers Squibb announces pivotal KRYSTAL-12 confirmatory trial evaluating KRAZATI (adagrasib) meets primary endpoint of progression-free survival for patients with pretreated KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer. News release. Bristol Myers Squibb. March 28, 2024. Accessed September 6, 2024. https://tinyurl.com/24e4swc6

11. AVEO Oncology, an LG chem company, announces phase 3 renal cell carcinoma clinical trial (TiNivo-2) results. News release. AVEO Oncology. July 18, 2024. Accessed September 6, 2024. https://tinyurl.com/unkz8k76

12. Bayer announces positive topline results for NUBEQA® (darolutamide) from phase III trial in men with metastatic hormone-sensitive prostate cancer (mHSPC). News release. Bayer. July 17, 2024. Accessed September 6, 2024. https://tinyurl.com/4639ejj9

13. Elyashiv O, Ledermann J, Parmar G, et al. ICON 9-an international phase III randomized study to evaluate the efficacy of maintenance therapy with olaparib and cediranib or olaparib alone in patients with relapsed platinum-sensitive ovarian cancer following a response to platinum-based chemotherapy. Int J Gynecol Cancer. 2021;31(1):134-138. doi:10.1136/ijgc-2020-002073

14. Mirza MR, González-Martín A, Graybill WS, et al. Prospective evaluation of the tolerability and efficacy of niraparib dosing based on baseline body weight and platelet count: Results from the PRIMA/ENGOT-OV26/GOG-3012 trial. Cancer. 2023;129(12):1846-1855. doi:10.1002/cncr.34706

15. Blank CU, Lucas MW, Scolyer RA, et al. Neoadjuvant nivolumab and ipilimumab in resectable stage III melanoma. N Engl J Med. Published online June 2, 2024. doi:10.1056/NEJMoa2402604