Key Advances in Oncology: Top Highlights From ESMO 2024

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This year's 2024 ESMO Congress brought forth a wave of groundbreaking developments poised to shape the future of oncology. As an essential platform for sharing pivotal cancer research and innovative clinical practices, the ESMO Congress continues to foster vital discourse among the medical community.

From novel therapeutic advancements to significant updates in cancer care protocols, these key insights are set to enhance clinical practice and patient outcomes.

Nivolumab & Tivozanib Fail in Renal Cell Carcinoma

The phase 3 TiNivo-2 study (NCT04987203) investigated the combination of nivolumab (Opdivo) and tivozanib (Fotivda) in patients with metastatic renal cell carcinoma (RCC) who had previously been treated with a PD-(L)1 inhibitor. Results showed no improvement in clinical outcomes with the combination therapy compared with tivozanib alone. The trial confirmed that rechallenging with immune checkpoint inhibitors offers limited benefits.

Adagrasib vs Docetaxel for KRAS G12C-Mutant NSCLC

Adagrasib (Krazati) demonstrated significantly better outcomes compared with docetaxel in previously treated KRAS G12C-mutated non–small cell lung cancer (NSCLC), including in patients with brain metastases, according to the phase 3 KRYSTAL-12 trial (NCT04685135). Treatment-related adverse effects (AEs) were comparable between the 2 treatments, with similar rates of AEs reported across both patient groups.

T-DXd Effective for HER2+ Breast Cancer with Brain Mets

Fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) demonstrated durable overall and intracranial activity in patients with HER2-positive metastatic breast cancer with stable and active brain metastases, as per the DESTINY-Breast12 study (NCT04739761). The study had a 12-month progression-free survival (PFS) rate of 61.6% across a cohort of 263 patients with brain metastases (95% CI, 54.9%-67.6%). This PFS was consistent across subgroups with stable and active metastases.

Pembrolizumab Improves Survival in Early-Stage TNBC

The phase 3 KEYNOTE-522 trial (NCT03036488) demonstrated that neoadjuvant pembrolizumab (Keytruda) combined with chemotherapy, followed by adjuvant pembrolizumab, significantly improved overall survival (OS) in early-stage triple-negative breast cancer (TNBC) compared with a placebo regimen.

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Lenvatinib and Pembrolizumab Effective for Thymic Tumors

Treatment with lenvatinib (Lenvima) plus pembrolizumab showed a 5-month PFS rate of almost 90% in patients with platinum refractory advanced B3-thymoma and thymic carcinoma without autoimmune disorders. Given the poor prognosis for thymic epithelial tumors and limited existing treatment options, the study highlights the clinical potential of this combination therapy for advanced disease stages.

LITESPARK-005: Belzutifan Shows Promise in Clear Cell RCC

Treatment with belzutifan (Welireg) showed significant benefits over everolimus (Afinitor) for advanced RCC, enhancing PFS and objective response rate (ORR). However, the LITESPARK-005 trial (NCT04195750) did not reveal a clear OS advantage.

The FDA approved belzutifan based on earlier trial results. It is now recommended as a treatment option post PD-(L)1 inhibitor and VEGF tyrosine kinase inhibitor therapy.

Promising Dato-DXd Findings for Endometrial & Ovarian Cancer

The phase 2 TROPION-PanTumor03 study (NCT05489211) showed that datopotamab deruxtecan (Dato-DXd) exhibited promising antitumor activity and manageable toxicity in patients with advanced ovarian and endometrial cancer post-platinum chemotherapy. AEs were comparable between both cohorts, with no treatment-emergent AE-related deaths. The study continues to explore Dato-DXd across various tumor types.

Melanoma Treatment Advances: Fianlimab & Cemiplimab

Fianlimab and cemiplimab (Libtayo) demonstrated significant and persistent clinical activity in patients with advanced melanoma, regardless of LAG-3 or PD-L1 expression, per a phase 1 trial (NCT03005782). At a median follow-up of 23 months, the ORR was 57%, with a complete response rate of 25% and a partial response rate of 33%.

Zipalertinib Effective in EGFR Exon 20-Mutated NSCLC

Zipalertinib (CLN-081, TAS6417) demonstrated promising efficacy and manageable safety in heavily pretreated patients with NSCLC with EGFR exon 20 insertion mutations, according to phase 2b REZILIENT1 trial (NCT04036682) data. The ORR was 40% (95% CI, 22.7%-59.4%) with 90% disease control rate (95% CI, 73.5%-97.9%). Common AEs included rash, paronychia, and anemia, which were seen in 38%, 36%, and 24% of the patients in the overall population (n = 30). The FDA previously granted zipalertinib breakthrough therapy designation, and it is now in a phase 3 trial (NCT05973773).

Radium-223 & Enzalutamide Boost Prostate Cancer Outcomes

Combining radium-223 (Xofigo) with enzalutamide (Xtandi) significantly improved radiological PFS and OS in patients with advanced prostate cancer with bone metastases, as proven in the PEACE-3 trial (NCT02194842). The mandatory addition of a bone-protecting agent was recommended. The safety profile indicated a higher incidence of AEs with the combination treatment compared with enzalutamide alone.

Discussions highlighted the need for more data before fully adopting this combination in clinical practice, despite the promising results.