ASCO 2025 Highlights: Breakthrough Cancer Treatments & Innovations in Immunotherapy and Breast Cancer

Thanks to the tremendous contributions of the pharmaceutical and biotechnology industries, over the past decades, treatment options and survival rates for patients with the world's deadliest cancers have significantly improved. Immunotherapies such as Opdivo, Tecentriq, and Imfinzi were first approved almost ten years ago and continue to push the boundaries of treatment today; bispecific antibodies, as relatively new members, are also actively exploring their clinical benefit limits.

How can innovation occur in fields originally lacking innovation? And how can we advance further based on existing innovations? The recently concluded ASCO Annual Meeting provided a "notebook" of answers.

At this ASCO meeting, pharmaceutical giants, biotechnology companies, researchers, and oncologists presented or published over 5,000 research abstracts. These abstracts included studies on existing drugs, experimental therapies, artificial intelligence tools, and concepts for improving patient care.

No matter the praise, new drug candidates require a long time before entering clinical practice. As for which data truly change clinical practice, more "meetings" are needed to judge.

Breast Cancer "Benefits"

This year's ASCO headlines featured encouraging clinical trial data on several drugs targeting different breast cancer subtypes.

The much-anticipated Enhertu, as part of first-line treatment for HER2-positive metastatic breast cancer, showed strong efficacy and may change the standard of care for this indication.

The experimental targeted drug vepdegestrant (ARV-471), jointly developed by Pfizer and Arvinas, holds promise to control a common type of breast cancer progression.

Camizestrant from AstraZeneca was shown to effectively maintain benefits in patients with a more common tumor type (estrogen receptor-positive breast cancer) in first-line treatment.

However, these good news come with important caveats.

Enhertu

In a large late-stage trial, the blockbuster drug Enhertu by AstraZeneca and Daiichi Sankyo significantly prolonged tumor growth for a specific breast cancer subtype when used as initial treatment. The trial results are expected to help expand Enhertu’s indications and change the treatment paradigm of this disease for the first time in a decade.

The trial evaluated Enhertu combined with the standard drug Perjeta (pertuzumab) as first-line treatment (for newly diagnosed HER2-positive metastatic breast cancer patients). Results showed patients receiving Enhertu combination therapy survived nearly 41 months before disease progression, compared to about 27 months for patients on standard treatment (THP: taxane combined with trastuzumab and pertuzumab).

AstraZeneca’s Executive Vice President of Oncology David Fredrickson stated that one-third of patients starting treatment for this cancer type are unable to receive second-line therapy due to health deterioration or death. However, results show Enhertu combination therapy can provide another third of patients with longer progression-free survival, enabling them to receive first-line treatment.

But this product also carries dangerous side effects, such as interstitial lung disease/pneumonitis and neutropenia. If approved for first-line treatment, physicians may use it more cautiously.

vepdegestrant (ARV-471)

The world’s first PROTAC entering phase III clinical trials and the headline of the largest PROTAC deal in 2021—oral drug vepdegestrant (ARV-471) data presented at this ASCO meeting show promise for treating estrogen receptor-positive but HER2-negative breast cancer patients.

Developed jointly by Pfizer and Arvinas, this PROTAC degrader leverages the body’s natural protein degradation system to specifically target and degrade the estrogen receptor (ER).

However, vepdegestrant’s efficacy advantage over the commonly used therapy fulvestrant is limited to patients carrying an ESR1 gene mutation; patients without this mutation appear not to benefit. Meanwhile, incorporating camizestrant (a SERD drug) into clinical practice will require broader adoption of a blood test for monitoring ESR1 mutations, which is complex and costly.

Nonetheless, the trial data offer doctors more options to control advanced breast cancer. Switching fulvestrant from intramuscular injection to oral administration (like vepdegestrant) is not a minor change—it can give patients more autonomy and significantly improve quality of life.

The "Achilles' Heel" of Bispecific Antibodies

In just a few years, bispecific antibodies have evolved from an exciting technological breakthrough to a common clinical practice option, used not only for treating advanced blood cancers but also some early-stage tumors. A large number of new bispecific antibodies are in clinical trials, making this field a hot spot for pharmaceutical industry deals.

However, these therapies generally carry immune-related side effects previously seen only in CAR-T cell therapies, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), both intense reactions caused by immune cell activation.

Take Amgen’s newly launched lung cancer drug Imdelltra (tarlatamab) as an example. According to late-stage trial data, for small-cell lung cancer patients whose disease progressed after first-line chemotherapy, tarlatamab reduced the risk of death by 40% compared to chemotherapy. Compared with standard chemotherapy care, Imdelltra also extended median overall survival by more than five months. Amgen said the trial results support last year’s FDA accelerated approval of Imdelltra.

However, more than half of patients in the key trial experienced CRS. About one-seventh experienced ICANS, usually within the first 30 days.

Some experts believe side effects can be monitored by providing patients with tools such as thermometers, blood pressure cuffs, and pulse oximeters, or suppressed by steroid drugs like dexamethasone.

More bispecific antibodies will emerge in solid tumor oncology, where side effects are unavoidable, especially in prostate and breast cancer patients where CRS may be more severe.

However, new targeted drugs may improve this situation.

Johnson & Johnson first disclosed clinical trial data for JNJ-78278343 (pasritamig), a bispecific T-cell engager (TCE) targeting KLK2/CD3, which activates patients’ own T cells to kill KLK2-expressing prostate cancer cells.

Data showed CRS occurred in only 8.9% of patients (all grade 1), with no grade ≥2 CRS or ICANS, and manageable safety. Among treatment tolerance, grade ≥3 treatment-related adverse events (TRAE) were only 4.4%, with no treatment interruptions or discontinuations, supporting outpatient dosing.

Clinical efficacy needs improvement: PSA50 response rate was 42.4%, objective response rate (ORR) was 16.1% (5/31) in lymph node ± bone metastasis patients, and 3.7% (2/54) in visceral disease patients.

This data release marked not only the drug project’s first public debut but also the first clinical data presentation for KLK2-targeted TCE (KLK2-TCE).

Veterans’ New Explorations

In a late-stage trial, Gilead’s popular drug Trodelvy combined with Merck’s blockbuster immunotherapy Keytruda reduced the risk of progression of an aggressive breast cancer by 35% when used as initial treatment.

The study targeted advanced triple-negative breast cancer patients whose tumors express PD-L1 protein (the target of drugs like Keytruda). Gilead noted that about 15% of breast cancer cases are triple-negative, which are more aggressive and harder to treat.

Experts say the Trodelvy-Keytruda combination "is very likely to become the new first-line standard of care in this context."

Similarly, Tecentriq combined with Lurbinectedin achieved positive results in the phase III IMforte study for extensive-stage small-cell lung cancer, showing significant survival benefits. In this aggressive cancer type with limited survival and treatment options, the risk of progression or death decreased by 46%, and risk of death decreased by 27%.

This is the first phase III regimen for extensive-stage small-cell lung cancer (ES-SCLC) first-line maintenance treatment to significantly improve both progression-free survival (PFS) and overall survival (OS), potentially replacing current Tecentriq or Imfinzi monotherapy maintenance.

AstraZeneca’s PD-L1 inhibitor Imfinzi combined with FLOT regimen for resectable gastric or gastroesophageal junction (GEJ) cancer perioperative treatment reduced event-free survival (EFS) risk by 29% (HR=0.71), with a 24-month EFS rate of 67.4%. Merck’s PD-1 inhibitor Keytruda in neoadjuvant/adjuvant treatment for head and neck squamous cell carcinoma significantly improved patients’ EFS, doubling median EFS to five years.

These studies suggest applying immune checkpoint inhibitors at earlier treatment stages and cleverly combining them with chemotherapy and surgery is key to improving efficacy.

However, not all “veterans” have smooth sailing in new indication explorations. The antibody-drug conjugate (ADC) patritumab deruxtecan (HER3-DXd), jointly developed by Merck and Daiichi Sankyo, is one such case.

Because the drug failed to prolong survival in lung cancer patients in late-stage trials, the companies have withdrawn the experimental treatment’s US marketing application.

However, last year, the drug achieved its primary endpoint: compared with chemotherapy, it helped delay tumor progression in previously treated non-small cell lung cancer patients carrying EGFR mutations.

Merck’s global clinical development head of oncology Marjorie Green said the “overall data were insufficient to support” the drug’s approval but the company is “fully committed” to improvements.