AstraZeneca Rebuilds Breast Cancer Treatment Around Enhertu, Datroway and a Blood Test

$2.96 Billion in Six Months

Combined Enhertu sales recorded by Daiichi Sankyo and AstraZeneca reached $2,961 million in the first half of 2026, from $2,289 million a year earlier, with US in-market sales of $1,440 million. AstraZeneca's reported Enhertu revenue grew 36% to $1,719 million, and the second quarter alone brought $888 million. The company attributes the US growth to "ongoing adoption in 1L HER2-positive breast cancer (DESTINY-Breast09)" and the emerging-market growth to China's reimbursement listing of the HER2-positive and HER2-low indications from Jan. 1, 2025.

DESTINY-Breast09 became a label on Dec. 15, 2025. The trial randomized 1,157 patients with untreated HER2-positive advanced disease to Enhertu at 5.4 mg/kg plus pertuzumab, to taxane-trastuzumab-pertuzumab, or to Enhertu alone. Median progression-free survival by blinded review was 40.7 months (95% CI 36.5 to not estimable) with Enhertu plus pertuzumab against 26.9 months for THP (HR 0.56, 95% CI 0.44-0.71), with confirmed response rates of 87% and 81%. Overall survival was immature at 16% of deaths across both arms when the FDA acted. The CHMP issued a positive opinion for the EU in July 2026, and the third arm, Enhertu without pertuzumab, is due to read in the second half of 2026 and will answer whether the antibody adds anything to the ADC. Final results of DESTINY-Breast07, which pairs Enhertu with durvalumab in the same setting, were presented at ASCO on May 31 (abstract 1012).

Shanu Modi's Two Approvals

The May 15, 2026 approvals took Enhertu into patients who may still be cured. In DESTINY-Breast11, four cycles of neoadjuvant Enhertu followed by four of THP produced a pathologic complete response in 67.3% of patients with stage II or III HER2-positive disease, against 56.3% for dose-dense doxorubicin and cyclophosphamide followed by THP, an 11.2-point difference (95% CI 3.9-18.3, p=0.003) in a 927-patient trial whose Enhertu-monotherapy arm was closed early on the data monitoring committee's advice. In DESTINY-Breast05, adjuvant Enhertu for patients with residual invasive disease after neoadjuvant trastuzumab and taxane cut the risk of invasive recurrence or death by 53% against trastuzumab emtansine (HR 0.47, 95% CI 0.34-0.66, p<0.0001), with 51 events against 102 and three-year invasive disease-free survival of 92.4% against 83.7%.

"The neoadjuvant setting offers the earliest opportunity to improve outcomes, while the adjuvant setting provides another important chance to prevent recurrence for patients with residual disease after surgery. These two new indications in HER2-positive early breast cancer will evolve how we treat patients in these settings and support trastuzumab deruxtecan as a potential new standard of care in early-stage disease," said Shanu Modi, MD, of Memorial Sloan Kettering Cancer Center.

Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 9.6% of the Enhertu arm of DESTINY-Breast05 against 1.6% on T-DM1, with seven grade 3 events and two deaths, and that number will follow the adjuvant indication into clinic. In the neoadjuvant trial, ILD rates matched the anthracycline arm while grade 3 or higher events, serious events and left ventricular dysfunction were lower. Both reviews ran under Project Orbis, the NCCN lists adjuvant Enhertu as a Category 1 option, and the approvals triggered $155 million in milestone payments from AstraZeneca to Daiichi Sankyo. Ken Keller, Daiichi Sankyo's global head of oncology business, counted "practice-changing data across six breast cancer indications in seven years."

Datroway Takes the Chemotherapy Slot in Triple-Negative Disease

The FDA approved Datroway on May 22, 2026, for unresectable or metastatic triple-negative breast cancer in patients who are not candidates for a PD-1 or PD-L1 inhibitor, a group AstraZeneca puts at roughly 70% of metastatic TNBC. TROPION-Breast02 randomized 644 untreated patients to Datroway at 6 mg/kg every three weeks or investigator's choice of chemotherapy, most often nab-paclitaxel (54%) or paclitaxel (28%). Median progression-free survival was 10.8 months against 5.6 (HR 0.57, 95% CI 0.47-0.69), median overall survival 23.7 months against 18.7 (HR 0.79, 95% CI 0.64-0.98, p=0.029), and confirmed response rates 64% and 30%. The label warns on ILD, ocular toxicity, stomatitis and embryo-fetal toxicity. The European Commission followed on July 31.

"Despite recent advances, more than two thirds of patients are not candidates for immunotherapy and have had limited options beyond chemotherapy," said Giuseppe Curigliano, MD, PhD, of the European Institute of Oncology, a TROPION-Breast02 investigator. AstraZeneca recorded $98 million of Datroway revenue in the first half, with combined AstraZeneca and Daiichi Sankyo sales of $225 million against $45 million a year earlier. Three more TROPION-Breast trials run behind it. TROPION-Breast03 randomizes 1,174 patients with residual disease after neoadjuvant therapy to Datroway with or without Imfinzi (durvalumab) against capecitabine, pembrolizumab or both, and reads in the second half of 2027. TROPION-Breast05 tests Datroway plus Imfinzi against chemotherapy plus pembrolizumab in 625 patients with PD-L1-positive metastatic disease on the same timeline, and TROPION-Breast04 covers 1,902 patients in the perioperative setting, with data after 2027.

Six Votes Against a Blood Test

SERENA-6 enrolled 315 patients on an aromatase inhibitor plus a CDK4/6 inhibitor as first-line treatment and drew blood for ctDNA at each routine scan, every two to three months. When an ESR1 mutation appeared without radiographic progression, the aromatase inhibitor was switched to camizestrant under double blind and the CDK4/6 inhibitor continued. The interim analysis, presented at ASCO in June 2025 with simultaneous NEJM publication, gave a progression-free survival hazard ratio of 0.44 and medians of 16.0 against 9.2 months.

The Oncologic Drugs Advisory Committee met on April 30, 2026, and voted 3 to 6. "Today's recommendation by the ODAC is disappointing, as new options and innovative treatment strategies which address emerging resistance ahead of disease progression and deterioration in quality of life are needed in the 1st-line setting," said Kevin Kalinsky, MD, of Emory's Winship Cancer Institute, an investigator on the trial. On May 27 the FDA extended the review to assess additional analyses, and, as BioPharma Dive reported the same day, did not assign a new action date.

The additional analyses were presented at ASCO on June 2 as LBA1007. With longer follow-up the PFS hazard ratio was 0.45 (95% CI 0.34-0.59) and the medians 16.8 against 9.2 months. Second progression-free survival, which AstraZeneca describes as a measure of durability beyond first progression, was 25.7 months against 19.1 (HR 0.63, 95% CI 0.46-0.86, p=0.00373). Overall survival stood at a hazard ratio of 0.87 (95% CI 0.57-1.30) at 30% maturity. Patients who switched had a median 99% fall in total ctDNA by week 8, with 51% clearing it entirely, against a median 64% rise and 1.9% clearance on the aromatase inhibitor, and in a pooled exploratory analysis clearance tracked with survival (HR 0.39, 95% CI 0.19-0.73). "More than half of patients who switched to the camizestrant combination completely cleared tumour DNA from their bloodstream compared to two per cent with standard of care," said Susan Galbraith, AstraZeneca's executive vice president for oncology hematology R&D.

Europe went the other way. The European Commission approved the combination as Etcamah on July 23, 2026, Japan approved it in June, and the United Arab Emirates and Saudi Arabia earlier. AstraZeneca counts Etcamah as the 11th of the 20 new medicines it expects to launch by 2030 and booked $3 million of sales from the first launch markets. "As the first pivotal trial to demonstrate the clinical value of monitoring circulating tumour DNA in the 1st-line breast cancer setting, SERENA-6 represents a significant advance in clinical practice and it is now important to identify patients who may be able to benefit from this combination and intervene promptly before their disease progresses," said François-Clément Bidard, MD, PhD, of Institut Curie, the trial's co-principal investigator.

SERENA-4 is the trial that answers the panel's objection on its own terms. It randomized 1,370 untreated patients to camizestrant plus palbociclib against anastrozole plus palbociclib, with no ctDNA trigger and a conventional comparator, and AstraZeneca lists its data for the second half of 2026. CAMBRIA-1, with 4,300 patients switched to camizestrant after two to five years of adjuvant endocrine therapy, reads in the second half of 2027, and CAMBRIA-2, 5,500 patients at intermediate-high or high risk of recurrence, completes enrollment in the third quarter of 2026. BioPharma Dive noted that the three oral SERDs already on the US market are cleared only for ESR1-mutant disease and none has yet proven itself as initial treatment.

Truqap Waits for Its First-Line Trial

Truqap (capivasertib) sold $431 million in the first half, up 43%, and AstraZeneca says it has "achieved peak share in second-line biomarker-altered metastatic breast cancer." The move to first line rests on CAPItello-292, 793 patients with early-relapse or endocrine-resistant disease randomized to Truqap plus palbociclib and fulvestrant or placebo, with data in the second half of 2027. The drug's one Phase III in triple-negative disease, CAPItello-290 with paclitaxel, missed overall survival in both the full population and the PIK3CA, AKT1 or PTEN-altered subgroup on June 18, 2024. Its most recent approval came in prostate cancer on June 12, 2026, for PTEN-deficient metastatic hormone-sensitive disease, where the combination cut the risk of radiographic progression or death by 19%. AstraZeneca is also pairing the PARP1-selective saruparib with camizestrant in BRCA-mutated, HR-positive disease.

Why This Matters to the APO|APE Reader

Every one of these approvals arrived with a testing requirement the lab has to meet. The DESTINY-Breast09 approval came with two companion diagnostics, the PATHWAY anti-HER2/neu (4B5) rabbit monoclonal antibody and the HER2 Dual ISH DNA probe cocktail, for IHC 3+ or ISH-positive status, and the DESTINY-Breast11 label specifies HER2 positivity "as determined by an FDA-authorised test." Datroway in triple-negative disease asks for no TROP2 assay at all. If the FDA follows Brussels and Tokyo on camizestrant, the SERENA-6 strategy turns serial ESR1 ctDNA testing every two to three months into a standing order for a first-line population AstraZeneca sizes at about 37,000 US patients, roughly 30% of whom develop an ESR1 mutation before progression, and the agency has still not said when it will decide. Two readouts in the second half of 2026 settle the next questions: the Enhertu monotherapy arm of DESTINY-Breast09 tells whether pertuzumab is still needed, and SERENA-4 tells whether camizestrant belongs in first line without a blood test.