ESMO 2025: The Top 10 Takeaways That May Shift Oncology Practice

Final data from the phase 3 ALEX trial (NCT02075840) demonstrated a meaningful improvement in overall survival with frontline alectinib vs crizotinib among patients with advanced ALK-positive NSCLC.

With the conclusion of the European Society for Medical Oncology (ESMO) Congress 2025 in Berlin, Germany, time will tell how data from several late-breaking abstracts, Q and A panels, poster presentations, and other key sessions will influence clinical practice across multiple cancer types. Throughout the meeting, experts highlighted critical developments in new potential treatment options in breast cancer, lung cancer, genitourinary cancer, and many other patient populations.

CancerNetwork® reported on the latest data across these treatment fields. Here are the top 10 articles on presentations from ESMO Congress 2025 that may shape patient care in the future.

#1: Frontline Alectinib Upholds OS Benefit in Advanced ALK+ NSCLC

Final data from the phase 3 ALEX trial (NCT02075840) demonstrated a meaningful improvement in overall survival (OS) with frontline alectinib (Alecensa) vs crizotinib (Xalkori) among patients with advanced ALK-positive non–small cell lung cancer (NSCLC).1 The median OS was 81.1 months (95% CI, 62.3-not estimable [NE]) vs 54.2 months (95% CI, 34.6-75.6) with alectinib and crizotinib, respectively (HR, 0.78; 95% CI, 0.56-1.08; stratified log-rank P = .1320).

According to presenting investigator Tony S. K. Mok, MD, FRCP(C), FRCP(Edin), FHKCP, FHKAM(Medicine), FASCO, the data observed with alectinib in this population may represent “one of the longest OS [rates]…ever reported for patients with stage IV [NSCLC].” Mok serves as the Li Shu Fan Medical Foundation Endowed Professor and chairman of the Department of Clinical Oncology at the Chinese University of Hong Kong in Sha Tin.

#2: Tarlatamab Plus Chemo/IO Regimens Are Safe, Elicit Responses in ES-SCLC

In the phase 1b DeLLphi-303 study (NCT05361395), combining tarlatamab-dlle (Imdelltra) with frontline chemoimmunotherapy and PD-L1 maintenance therapy produced encouraging efficacy and safety outcomes among those with extensive-stage small cell lung cancer (ES-SCLC).2 After a median follow-up of 13.8 months (95% CI, 12.5-15.0), data showed an objective response rate (ORR) of 71% (95% CI, 61%-80%), a median duration of response (DOR) of 11.0 months (95% CI, 8.5-NE), and a disease control rate of 82% (95% CI, 73%-89%).

Lead study author Martin Wermke, MD, director of the Trial Management/Early Clinical Trial Unit at the National Center for Tumor Diseases Dresden of the German Cancer Research Center at University Hospital Carl Gustav Carus in Germany, noted that findings from DeLLphi-303 supported continued investigation of tarlatamab-based treatment in the phase 3 DeLLphi-312 study (NCT07005128).

#3: Pembrolizumab Combo Significantly Improves PFS/OS in Recurrent Ovarian Cancer

Among patients with PD-L1–expressing platinum-resistant recurrent ovarian cancer (PRROC) in the phase 3 ENGOT-ov65/KEYNOTE-B96 trial (NCT05116189), pembrolizumab (Keytruda) plus chemotherapy with or without bevacizumab (Avastin) significantly improved progression-free survival (PFS) vs placebo plus chemotherapy.3 At the time of the second interim analysis, the median PFS was 8.3 months in the pembrolizumab arm vs 7.2 months in the placebo arm among those with a PD-L1 combined positive score of 1 or higher (HR, 0.75; 95% CI, 0.61-0.91). Data also showed respective median PFS values of 8.3 months and 6.4 months across the intent-to-treat population (HR, 0.73; 95% CI, 0.62-0.86).

Presenting investigator Nicoletta Colombo, MD, PhD, of the Gynecologic Oncology Program at the European Institute of Oncology in Milan, Italy, and the Department of Medicine and Surgery at the University of Milan-Bicocca, stated these data “support the use of pembrolizumab plus weekly paclitaxel, with or without bevacizumab, as a new standard of care for patients with PRROC.”

#4: Cancer Vaccine/Pembrolizumab Improves PFS in Treatment-Naive Melanoma

An investigational cancer vaccine, IO102-IO103, meaningfully improved PFS when administered in combination with pembrolizumab for patients with previously untreated advanced melanoma in the phase 3 IOB-013/KN-D18 trial (NCT05155254).4 Findings revealed a median PFS of 19.4 months (95% CI, 9.7-not reached) with the vaccine combination vs 11.0 months (95% CI, 6.0-14.8) using pembrolizumab alone (HR, 0.77; 95% CI, 0.58-1.00; P = .0558).

According to presenting author Jessica C. Hassel, MD, head of the Section of Dermato-Oncology of the Department of Dermatology at the National Center for Tumor Diseases and part of the CCC director board at Heidelberg University in Germany, results from the trial “support the potential benefit of this immune-modulatory cancer vaccine in combination with pembrolizumab for patients with untreated, advanced melanoma.”

#5: Regorafenib/Nivolumab Exhibits Nonsuperior Survival in Gastric Cancer

In a presentation on data from the phase 3 INTEGRATEIIb (NCT04879368) trial, David Goldstein, MBBS, FRACP, PRCP, stated that regorafenib (Stivarga) plus nivolumab (Opdivo) “was not superior to the investigator’s choice of chemotherapy in third- or later-line treatment” among those with previously treated, refractory advanced gastric or gastroesophageal junction cancer.5

Data highlighted by Goldstein, conjoint clinical professor and senior staff specialist in the Department of Medical Oncology at Prince of Wales Hospital in Sydney, Australia, revealed a median OS of 5.9 months in the regorafenib arm vs 6.3 months in the chemotherapy arm (HR, 0.88; 95% CI, 0.71-1.09; P = .23). However, the experimental regimen conferred a higher ORR at 7.4% vs 2.6% with chemotherapy (OR, 2.99; 95% CI, 1.00-12.11) without any detriment to global quality of life (QOL).

#6: Tarlatamab Improves Survival vs Chemotherapy in Second-Line SCLC Subgroups

Regardless of different chemotherapy-free intervals (CFIs) or prior receipt of anti–PD-L1 therapy among patients with SCLC in the phase 3 DeLLphi-304 trial (NCT05740566), tarlatamab appeared to prolong OS compared with chemotherapy.6 Across different patient subgroups, tarlatamab improved OS among those with a CFI of less than 90 days (HR, 0.60; 95% CI, 0.43-0.84), a CFI of at least 90 days (HR, 0.65; 95% CI, 0.45-0.93), prior treatment with anti–PD-L1 therapy (HR, 0.61; 95% CI, 0.45-0.82), and no prior anti–PD-L1 agents (HR, 0.65; 95% CI, 0.42-1.03).

Overall, findings from the DeLLphi-304 trial “reinforce the use of tarlatamab as a standard of care in second-line SCLC, including those patients with worse prognosis, such as [those] with platinum-resistant disease,” according to presenting author Pedro F. Simoes da Rocha, MD, PhD, of Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology in Barcelona, Spain.

#7: Lenvatinib/Everolimus Beats Cabozantinib in Phase 2 RCC Study

Among patients with metastatic clear cell renal cell carcinoma (RCC) in a phase 2 study (NCT05012371), combining lenvatinib (Lenvima) with everolimus (Afinitor) reduced the risk of disease progression or death vs cabozantinib (Cabometyx).7 The median PFS was 15.7 months with the lenvatinib regimen and 10.2 months with cabozantinib alone (HR, 0.51; 95% CI, 0.29-0.89; P = .02).

This trial was the “first head-to-head randomized comparison of contemporary second-line or later treatments after immune checkpoint inhibition,” and the outcomes “are relevant to treatment sequencing and inform[ing] oncology practice,” according to presenting author Andrew W. Hahn, MD, an assistant professor in the Department of Genitourinary Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston.

#8: ASCENT-03 Trial Supports Standard Use of Sacituzumab Govitecan in mTNBC

Findings from the phase 3 ASCENT-03 trial (NCT05382299) may “support a potential new standard” among “patients with triple-negative breast cancer when they develop metastasis and are unable to receive immune checkpoint inhibitors,” stated presenting investigator Javier C. Cortés, MD, PhD, head of the International Breast Cancer Center in Barcelona, Spain.8

In the trial, sacituzumab govitecan-hziy (Trodelvy) produced a median PFS of 9.7 months (95% CI, 8.1-11.1) vs 6.9 months (95% CI, 5.6-8.2) with chemotherapy (HR, 0.62; 95% CI, 0.50-0.77; P < .001). Moreover, sacituzumab govitecan improved the median DOR at 12.2 months (95% CI, 9.7-13.8) vs 7.2 months (95% CI, 5.7-8.4) in the comparator arm.

#9: Adjuvant Therapy Confers Postoperative ctDNA Clearance, DFS Benefit in CRC

In the INTERCEPT CRC study, adjuvant therapy demonstrated the ability to clear circulating tumor DNA (ctDNA) among patients with colorectal cancer (CRC) and ctDNA positivity following surgery.9 Of note, disease-free survival (DFS) outcomes were significantly improved in patients with ctDNA clearance on results from at least 2 tests among those with stage I to III CRC (P < .0001) and stage IV disease (P < .0001).

Based on these findings, presenting author Emerik Osterlund, MD, PhD, a postdoctoral fellow in gastrointestinal medical oncology at The University of Texas MD Anderson Cancer Center, said that “ctDNA clearance is useful for seeing potential benefit in novel therapeutic studies.”

#10: Subgroup Analysis Yields Clinically Meaningful Responses With T-DXd in HER2+ Breast Cancer

Across different subgroups of patients with HER2-positive advanced or metastatic breast cancer based on factors such as PIK3CA mutations, hormone receptor status, and prior treatment, fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) plus pertuzumab (Perjeta) meaningfully improved PFS vs paclitaxel plus trastuzumab and pertuzumab in the phase 3 DESTINY-Breast09 trial (NCT04784715).10 These subgroup findings were presented by Sibylle Loibl, MD, PhD, chair and CEO of the German Breast Group and associate professor of obstetrics and gynecology at the Goethe University of Frankfurt in Germany.

Data revealed a PFS benefit with T-DXd regimen in patients with de novo disease (HR, 0.49; 95% CI, 0.35-0.70), recurrent disease (HR, 0.63; 95% CI, 0.46-0.87), hormone receptor–positive status (HR, 0.61; 95% CI, 0.44-0.84), hormone receptor–negative status (HR, 0.52; 95% CI, 0.37-0.73), PIK3CA-mutated disease (HR, 0.52; 95% CI, 0.35-0.77), and no PIK3CA mutations (HR, 0.57; 95% CI, 0.43-0.77).

References

1. Peters S, Camidge DR, Dziadziuszko R, et al. Alectinib versus crizotinib in previously untreated ALK-positive advanced non-small cell lung cancer: final overall survival analysis of the phase III ALEX study. Ann Oncol. Published online October 17, 2025. doi:10.1016/j.annonc.2025.09.018
2. Wermke M, Lau SCM, Moskovitz M, et al. Tarlatamab with first-line chemoimmunotherapy for extensive stage small cell lung cancer (ES-SCLC): DeLLphi-303 study. Abstract presented at: European Society for Medical Oncology Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract 2757O.
3. Colombo N, Zsiros E, Sebastianelli A, et al. Pembrolizumab vs placebo plus weekly paclitaxel ± bevacizumab in platinum-resistant recurrent ovarian cancer: results from the randomized double-blind phase 3 ENGOT-ov65/KEYNOTE-B96 study. Abstract presented at: European Society for Medical Oncology Congress 2025; October 17–21, 2025; Berlin, Germany. Abstract LBA3.
4. Hassel JC, Arance AM, Carlino MS, et al. IO102-IO103 cancer vaccine plus pembrolizumab for first-line (1L) advanced melanoma: primary phase III results (IOB-013/KN-D18). Abstract presented at: European Society for Medical Oncology Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA53.
5. Goldstein D, Sjoquist K, Espinosa D, et al. Regorafenib plus nivolumab vs investigator’s choice of chemotherapy in previously treated gastric or gastroesophageal cancer: INTEGRATE IIb, a randomized phase 3 AGITG Intergroup [NHMRC-CTC/IKF/AIO, ACCRU, TCOG/NHRI] study. Abstract presented at: European Society for Medical Oncology Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA80.
6. Rocha P, Sun L, Cho BC, et al. Tarlatamab as second-line (2L) treatment for small cell lung cancer (SCLC): outcomes by chemotherapy-free interval (CFI) and prior PD-(L)1 inhibitor use in the phase 3 DeLLphi-304 trial. Abstract presented at: European Society for Medical Oncology Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA101.
7. Hahn AW, Chahoud J, Skelton W, et al. LenCabo: a randomized phase II multicenter trial of lenvatinib plus everolimus (len/eve) versus (vs) cabozantinib (cabo) in patients (pts) with metastatic clear cell RCC (ccRCC) that progressed on PD-1 immune checkpoint inhibition (ICI). Abstract presented at: European Society for Medical Oncology Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA94.
8. Cortés JC, Bardia A, Punie K, et al. Primary results from ASCENT-03: a randomized phase III study of sacituzumab govitecan (SG) vs chemotherapy (chemo) in patients (pts) with previously untreated advanced triple-negative breast cancer (TNBC) who are unable to receive PD-(L)1 inhibitors (PD-[L]1i). Abstract presented at: European Society for Medical Oncology Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA20.
9. Osterlund E, Maddalena G, Pellatt AJ, et al. Circulating tumour DNA (ctDNA) clearance and correlation with outcome in the INTERCEPT colorectal cancer (CRC) study. Abstract presented at: European Society for Medical Oncology Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract 732MO.
10. Loibl S, Jiang Z, Barroso-Sousa R, et al. Trastuzumab deruxtecan (T-DXd) + pertuzumab vs taxane + trastuzumab + pertuzumab (THP) for patients with HER2+ advanced/metastatic breast cancer: additional analyses of DESTINY-Breast09 in key subgroups of interest. Abstract presented at: European Society for Medical Oncology Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA18.