ASCO 2025: The Presentations That May Shift the Cancer Care Paradigm

Updated findings from the phase 3 SERENA-6 trial (NCT04964934) may validate ESR1 mutations as an actionable biomarker when using camizestrant, a novel selective estrogen receptor degrader (SERD), in combination with CDK4/6 inhibitors for those with hormone receptor (HR)–positive, HER2-negative advanced breast cancer.

One of the biggest annual meetings in clinical oncology is almost here.

Clinicians and researchers from around the world are gearing up for the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, which will feature key developments in cancer management across several different disciplines and disease types. From investigational therapies to novel screening techniques, from breast cancer tumors to head and neck malignancies, presenters will highlight progress from all corners of the oncology world.

With an abundance of potentially practice-changing sessions on the horizon, CancerNetwork® connected with experts with solid tumor oncology backgrounds to learn more about the presentations that may stand out from the rest. Here is a sample of the late-breaking abstracts and other sessions of interest that may transform the treatment paradigm:

A Breast Cancer Compendium

LBA109: Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1 positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study.

Presentation: May 31, 3:35-3:47 pm CDT by Sara M. Tolaney, MD, MPH

At ASCO 2025, investigators of the phase 3 ASCENT-04/KEYNOTE-D19 study (NCT05382286) will unveil the primary results of using sacituzumab govitecan-hziy (Trodelvy) in combination with pembrolizumab (Keytruda) as a treatment for patients with inoperable, PD-L1–positive, triple-negative breast cancer (TNBC). Findings from this session will reveal how outcomes with the sacituzumab govitecan combination compare with standard-of-care treatment with pembrolizumab plus chemotherapy related to the primary end point of progression-free survival (PFS) as well as other end points such as overall survival (OS) and duration of response (DOR).

“ASCENT-04 may take another antibody drug conjugate [ADC], sacituzumab govitecan, plus pembrolizumab to the first-line setting for PD-L1–positive TNBC. Given the major unmet need represented by this disease, any improvement in outcomes is very welcome and relevant,” Paolo Tarantino, MD, PhD, a clinical research fellow at Dana-Farber Cancer Institute and Harvard Medical School, stated in a written comment to CancerNetwork.

In April 2025, developers announced topline results from the ASCENT-04 trial showing that treatment with the sacituzumab govitecan combination produced a clinically meaningful and statistically significant PFS improvement vs pembrolizumab/chemotherapy.1 Data also showed a trend toward prolonged OS with the investigational combination, although they were not mature at the time of data cutoff.

“For patients with metastatic [TNBC], there is a critical need for more effective treatment options,” lead trial investigator Sara M. Tolaney, MD, MPH, associate professor of medicine at Harvard Medical School, chief of the Division of Breast Oncology at the Dana-Farber Cancer Institute, said in a press release on these findings.1 “These data suggest that the combination of sacituzumab govitecan and pembrolizumab may offer a new treatment approach, bringing together a potent [ADC] with immunotherapy to improve outcomes for patients.”

LBA1008: Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (a/mBC): interim results from DESTINY-Breast09.

Presentation: June 2, 7:30-7:42 AM CDT by Sara M. Tolaney, MD, MPH

Another breast cancer presentation of interest includes a late-breaking abstract on the phase 3 DESTINY-Breast09 trial (NCT04784715). The session will feature interim analysis results achieved with fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) plus pertuzumab (Perjeta) vs a taxane plus trastuzumab (Herceptin) and pertuzumab (THP) as frontline therapy for patients with advanced or metastatic HER2-positive breast cancer.

In April 2025, developers announced topline results from the DESTINY-Breast09 trial, which demonstrated a PFS improvement with the T-DXd combination across all prespecified patient subgroups.

“The highly awaited [DESTINY-Breast09] phase 3 trial will report on the benefit of advancing T-DXd [with or without] pertuzumab to the first-line setting, challenging the traditional ‘CLEOPATRA’ [NCT00567190] regimen [of THP],” Tarantino wrote to CancerNetwork. “The trial was announced to be positive and is expected to set a new standard of care, although it will raise several important questions. It will be important to review the toxicity profile of the regimen (particularly interstitial lung disease [ILD]) and to understand whether an induction strategy may still be considered rather than indefinite T-DXd treatment.”

LBA4: Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): phase 3, double-blind ctDNA-guided SERENA-6 trial.

Presentation: June 1, 2:41-2:53 PM CDT by Nicholas C. Turner, MD, PhD

Updated findings from the phase 3 SERENA-6 trial (NCT04964934) may validate ESR1 mutations as an actionable biomarker when using camizestrant, a novel selective estrogen receptor degrader (SERD), in combination with CDK4/6 inhibitors for those with hormone receptor (HR)–positive, HER2-negative advanced breast cancer.

In February 2025, developers announced topline results from SERENA-6 showing a statistically significant and clinically meaningful PFS improvement with frontline camizestrant-based treatment vs standard-of-care therapy in this population.3 Although data were immature at the time of analysis, investigators also noted a trend towards improved time to second disease progression (PFS2) with the investigational regimen.

“If a patient is found to have an ESR1 mutation, the question [of SERENA-6] is whether we should switch aromatase inhibitors….We know that hormone-blocking therapies do not work well in this scenario,” MinhTri Nguyen, MD, a medical oncologist and hematologist at Stanford Health Care, said in an interview with CancerNetwork about this study. “If we were to use a medication like camizestrant in that space instead? That’s something that would be practice-changing not only treatment-wise but also for following patients surveillance-wise. How do we find these mutations in the first place if we are not looking for them? Perhaps part of the surveillance would be to look for these mutations in patients.”

Key Updates in Gastrointestinal Cancers

LBA1: Randomized trial of standard chemotherapy alone or combined with atezolizumab as adjuvant therapy for patients with stage III deficient DNA mismatch repair (dMMR) colon cancer.

Presentation: June 1, 1:05-1:17 PM CDT by Frank A. Sinicrope, MD

In a written correspondence with CancerNetwork, Mehmet Sitki Copur, MD, FACP, a medical director of Oncology and adjunct professor of Medical Oncology/Hematology at the University of Nebraska Medical Center, a medical oncologist/hematologist at Morrison Cancer Center of Mary Lanning Healthcare, and gastrointestinal (GI) editorial advisory board member for the journal ONCOLOGY, outlined several noteworthy presentations in the GI malignancy space.

According to Copur, some of the most “early and long-awaited results” from the National Clinical Trials Network (NCTN) studies slated for presentation at this year’s ASCO meeting will come from the phase 3 ATOMIC trial (NCT02912559). Here, investigators are evaluating chemotherapy alone or in combination with atezolizumab (Tecentriq) as a potential adjuvant therapeutic strategy for those with stage III mismatch repair-deficient (dMMR) colon cancer.

“Although we have guideline-established data for the use of immunotherapy for dMMR colorectal cancer in [patients with] neoadjuvant and metastatic [disease], high-level data in the adjuvant setting have not been available,” Copur stated. “While the [ATOMIC] trial did not have a single-agent immunotherapy arm, it will provide crucial information regarding the addition of immunotherapy to standard adjuvant chemotherapy. Results of this study will certainly be practice-changing and will guide oncology providers in the adjuvant treatment setting for dMMR colon cancer.”

LBA3500: First-line encorafenib + cetuximab + mFOLFOX6 in BRAF V600E-mutant metastatic colorectal cancer (BREAKWATER): Progression-free survival and updated overall survival analyses.

Presentation: May 30, 2:45-2:57 PM CDT by Elena Elez, MD, PhD

Another presentation will include additional results from the phase 3 BREAKWATER trial (NCT04607421) assessing frontline encorafenib (Braftovi) plus cetuximab (Erbitux) and modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) for those with BRAF V600E-mutated metastatic colorectal cancer (CRC).

The encorafenib-based combination earned accelerated approval from the FDA for this patient population in December 2024 based on prior results from the BREAKWATER trial.4 The agency made its decision based on response data from the study; at the time of analysis, the encorafenib regimen elicited an overall response rate (ORR) of 61% (95% CI, 52%-70%) and a median duration of response (DOR) of 13.9 months (95% CI, 6.7-12.7).

According to Copur, the trial’s dual primary end point of PFS was event-driven, and data were not yet mature at the data cutoff. Following the combination’s accelerated approval, additional results from the BREAKWATER trial may elucidate the survival benefits of this treatment for patients with BRAF V600E-mutated metastatic CRC.

“Full details of the study will be provided and eagerly awaited,” Copur noted.

4006: Preliminary results from the randomized phase 2 study (1801 part 3B) of elraglusib in combination with gemcitabine/nab-paclitaxel (GnP) versus GnP alone in patients (pts) with previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC).

Presentation: May 31, 4:36-4:48 PM CDT by Devalingam Mahalingam, MD

One presentation in the pancreatic cancer space will focus on preliminary findings from the phase 2 Actuate-1801 part 3B study (NCT03678883) evaluating elraglusib plus gemcitabine/nab-paclitaxel (GnP) vs GnP alone as first-line therapy for those with metastatic pancreatic ductal adenocarcinoma (PDAC).

In May 2025, developers announced topline findings from the phase 2 study showing that the novel therapeutic combination significantly improved OS, meeting its primary end point.5 Additionally, the regimen was associated with a favorable risk-benefit profile.

“Elraglusib is a novel glycogen synthase kinase-3β [GSK-3β] inhibitor targeting molecular pathways in cancer that are involved in promoting tumor growth and resistance to conventional cancer drugs. Elraglusib may also mediate anti-tumor immunity through the regulation of multiple immune checkpoints and immune cell function,” Copur stated. “Novel treatment options in a difficult-to-treat cancer like [PDAC] are an unmet need and eagerly awaited.”

Head and Neck Data Headed for ASCO

6012: Neoadjuvant and adjuvant pembrolizumab plus standard of care (SOC) in resectable locally advanced head and neck squamous cell carcinoma (LA HNSCC): Exploratory efficacy analyses of the phase 3 KEYNOTE-689 study.

Presentation: June 1, 11:30-11:36 AM CDT by Douglas Adkins, MD

Key findings with regulatory implications in the head and neck cancer (HNC) world may come from the phase 3 KEYNOTE-689 trial (NCT03765918) assessing pembrolizumab (Keytruda) plus surgery and radiotherapy for those with locally advanced head and neck squamous cell carcinoma (HNSCC). At ASCO 2025, investigators will present exploratory efficacy outcomes from this trial that may support this regimen as a new potential standard of care.

The FDA granted priority review to a supplemental biologics license application (sBLA) for pembrolizumab-based treatment in this HNSCC population in February 2025 based on data from the KEYNOTE-689 trial.6 The Prescription Drug User Fee Act (PDUFA) date for this application is June 23, 2025. At the time of the agency’s priority review designation, topline data from KEYNOTE-689 demonstrated a statistically significant and clinically meaningful event-free survival (EFS) improvement with perioperative pembrolizumab therapy.

“The current standard of care for a majority of these patients includes surgery followed by radiation with or without chemotherapy. The chance of curing patients with the current standard of care is just under 50%. There lies the problem: a large number of patients unfortunately develop recurrence of their cancer after the standard-of-care treatment,” lead study presenter Douglas R. Adkins, MD, associate professor of Internal Medicine, Division of Oncology, Section of Medical Oncology at Washington University School of Medicine in St. Louis, Missouri, said in an interview with CancerNetwork ahead of the meeting. “These data are compelling data that I anticipate will alter the standard-of-care treatment for patients with locally advanced resectable [HNC].”

LBA2: NIVOPOSTOP (GORTEC 2018-01): a phase III randomized trial of adjuvant nivolumab added to radio-chemotherapy in patients with resected head and neck squamous cell carcinoma at high risk of relapse.

Presentation: June 1, 1:37-1:49 PM CDT by Jean Bourhis Sr, MD, PhD

In January 2025, the Head and Neck Radiation Oncology Group (GORTEC), an organization from France, announced topline results from the phase 3 NIVOPOSTOP GORTEC 2018-01 trial (NCT03576417) showing that nivolumab (Opdivo) following chemoradiotherapy improved disease-free survival (DFS) among patients with locally advanced HNSCC.7

According to lead study investigator Jean Bourhis, Sr, MD, PhD, chair of Radiation Oncology at CHUV Ludin Family Brain Tumour Research Centre, and co-founder and chairman of GORTEC, this outcome was “the first time in decades” where a novel treatment showed “superiority over standard-of-care cisplatin/radiotherapy” among patients with high-risk locally advanced HNSCC.7 As part of a late-breaking abstract at this year’s meeting, Bourhis will present detailed findings from a study that may change the landscape for this patient population.

“Both pembrolizumab and nivolumab are a type of immunotherapy drug... [that give] the opportunity to enhance the immune response to reducing the chance of recurrence,” Adkins stated regarding the NIVOPOSTOP trial. “I’m looking forward to seeing these results, and I am excited to see how they may also impact the standard-of-care treatment, particularly in Europe, where the trial was conducted.”

6015: Phase 2 open-label study of brentuximab vedotin (BV) + pembrolizumab (pembro) in patients (pts) with treatment (tx)-naive metastatic head and neck squamous cell carcinoma (HNSCC).

Presentation: June 1, 12:00-12:06 PM CDT by Cristina P. Rodriguez, MD

Another session to look out for may include a readout of data from a phase 2 study (NCT04609566) of brentuximab vedotin (Adcetris) plus pembrolizumab for patients with untreated metastatic HNSCC. Investigators of this multi-cohort trial are assessing the activity of this novel combination across several different types of cancer in addition to HNSCC, which include non–small cell lung cancer (NSCLC) and melanoma.8

At the 2024 ASCO Annual Meeting, investigators reported the immunomodulatory capacity of the brentuximab vedotin combination as well as encouraging OS outcomes among patients with metastatic NSCLC and cutaneous melanoma who progressed on prior anti–PD-1 treatment.9

“An interesting and novel concept of combining brentuximab vedotin and pembrolizumab in HNSCC to explore if targeting CD30-positive T-regulatory cells with [brentuximab vedotin] will enhance the immune response and improve treatment outcomes was tested in a phase 2 open-label study,” Copur wrote. “[This study] will be another important presentation in the rapid oral abstract session [for HNSCC].”

References

1. Trodelvy plus Keytruda demonstrates a statistically significant and clinically meaningful improvement in progression free survival in patients with previously untreated PD-L1+ metastatic triple-negative breast cancer. News release. Gilead Sciences Inc. April 21, 2025. Accessed May 16, 2025. https://tinyurl.com/3r97auu4
2. ENHERTU (fam-trastuzumab deruxtecan-nxki) plus pertuzumab demonstrated highly statistically significant and clinically meaningful improvement in progression-free survival vs. THP as 1st-line therapy for patients with HER2-positive metastatic breast cancer. News release. AstraZeneca. April 21, 2025. Accessed May 16, 2025. https://tinyurl.com/ycxdtrvw
3. Camizestrant demonstrated highly statistically significant and clinically meaningful improvement in progression-free survival in 1st-line advanced HR-positive breast cancer with an emergent ESR1 tumour mutation in SERENA-6 phase III trial. News release. AstraZeneca. February 26, 2025. Accessed May 16, 2025. https://tinyurl.com/322nhnks
4. FDA grants accelerated approval to encorafenib with cetuximab and mFOLFOX6 for metastatic colorectal cancer with a BRAF V600E mutation. News release. FDA. December 20, 2024. Accessed May 16, 2025. https://tinyurl.com/4utu3tdr
5. Actuate Therapeutics announces statistically significant topline results from global phase 2 trial of elraglusib in first-line treatment of metastatic pancreatic cancer. News release. Actuate Therapeutics, Inc. May 6, 2025. Accessed May 16, 2025. https://tinyurl.com/muk4y9a2
6. FDA grants priority review to Merck’s application for KEYTRUDA® (pembrolizumab) plus standard of care as perioperative treatment for resectable locally advanced head and neck squamous cell carcinoma. News release. Merck. February 25, 2025. Accessed May 16, 2025. https://tinyurl.com/yeypvde6
7. GORTEC announces new trial success for head and neck cancer treatment. News release. GORTEC. January 7, 2025. Accessed May 16, 2025. https://tinyurl.com/5n8wuez7
8. Brentuximab vedotin with pembrolizumab in metastatic solid tumors. ClinicalTrials.gov. Updated May 13, 2025. Accessed May 16, 2025. https://tinyurl.com/5n9bybdk
9. Zakharia Y, Lee S, Jotte RM, et al. Phase 2 trial of brentuximab vedotin (BV) with pembrolizumab (pembro) in patients with previously treated metastatic non-small cell lung cancer (NSCLC) or cutaneous melanoma (SGN35-033): overall survival. J Clin Oncol. 2024;42(suppl 16):2617. doi:10.1200/JCO.2024.42.16_suppl.2617