TROP2 ADCs: A Major Innovation for 1L TNBC
Gilead’s Trodelvy has made a name for itself in breast cancer, but recently Daiichi Sankyo AstraZeneca’s competing TROP2 ADC, Datroway, has beaten Trodelvy to market in 1L TNBC, a patient segment with traditionally no treatment options aside from chemotherapy alone. Approved one month apart from each other, Datroway has the stronger data, but Trodelvy has a broader label and physician experience on its side.
Approval Histories
In April 2020, Immunomedics’ novel TROP2 ADC, Trodelvy (sacituzumab govitecan-hziy), was granted accelerated approval for the treatment of relapsed or refractory triple-negative breast cancer (R/R TNBC), making it the first ADC approved by the FDA for this indication. Gilead went on to acquire Immunomedics and Trodelvy six months after its initial approval. Trodelvy was granted full approval in R/R TNBC in April 2021 and accelerated approval in pre-treated HR+/HER2- metastatic breast cancer in February 2023. Along the way, Gilead picked up and subsequently voluntarily withdrew an accelerated approval for the ADC in metastatic urothelial cancer.
No new TROP2 ADC had been approved since Trodelvy until January 2025, when Daiichi Sankyo and AstraZeneca’s Datroway (datopotamab deruxtecan-dlnk) was approved in pre-treated HR+/HER2- metastatic breast cancer, almost two years after Trodelvy’s approval in this indication. Datroway’s next approval came in June 2025 for pre-treated EGFR-mutated non-small cell lung cancer (NSCLC), an accelerated approval based on response rates from a pooled subgroup analysis of a broader population, beating Trodelvy to launch in lung cancer.
Clinical Data Summary
Now, within just one month of each other, the two TROP2 ADCs have each gained approval in previously-untreated TNBC, a patient population which to date has had chemotherapy as their only option in immunotherapy (IO)-ineligible patients. Datroway was first to be approved in 1L TNBC ineligible for IO, boasting an impressive 43% reduction in disease progression or death (PFS HR 0.57, p<0.0001) and 21% reduction in mortality, statistically significant at the 5% threshold (OS HR 0.79, p 0.0290) [1]. Trodelvy, just one month later, received approval regardless of a patient’s PD-L1 status, a broader population than that of Datroway. Trodelvy’s overall survival data are immature across both of its 1L TNBC populations, but its PFS benefits are still significant. In the PD-L1-negative/IO-ineligible segment, Trodelvy reduced the risk of disease progression or death by 38% (PFS HR 0.62, p<0.001)[2] compared to Datroway’s 43% reduction. For patients with a PD-L1 combined positive score (CPS) ≥ 10, Trodelvy + Merck’s Keytruda (pembrolizumab) boast a PFS HR = 0.65 (p<0.001) when compared to Keytruda + chemotherapy [3].
Equinox Group’s Analysis
Compared to their respective control arms in the IO-ineligible population, Datroway looks highly innovative using Equinox Group’s Disease Target Assessment (DTA) framework, reducing medical need by 10.6%; historically, improvements ≥10% become leaders in their market segments.
Clinical Innovation is displayed graphically in the below waterfall chart, where the unmet need score of the comparator regimen (chemotherapy) is represented on the left and the entrant (Datroway) on the right. Unmet need is scored on a 0-5 scale, with lower scores representing less unmet medical need. The individual green and red bars total to a regimen’s Clinical Innovation score.
Figure 1: Drivers of Clinical Innovation – Datroway in 1L TNBC ineligible for IO
In comparison, Trodelvy’s weaker PFS benefit and immature (and insignificant at this time) OS data produce a less favorable gain, with a net Clinical Innovation score of -0.7%, essentially looking equivalent to chemotherapy.
Figure 2: Drivers of Clinical Innovation – Trodelvy in 1L TNBC ineligible for IO
Compared against each other, Datroway’s Clinical Innovation score is 6.7%, significantly differentiated against Trodelvy.
Figure 3: Drivers of Clinical Innovation – Datroway vs. Trodelvy in 1L TNBC ineligible for IO
Trodelvy’s story is rosier in the PD-L1-positive cohort, delivering a 7.2% reduction in unmet medical need when combined with Keytruda, compared to chemotherapy plus Keytruda—a competitive Clinical Innovation score.
Figure 4: Drivers of Clinical Innovation – Trodelvy in 1L TNBC, PD-L1-positive
Share Prediction
With the innovation scores above and low levels of existing competition, Equinox Group predicts that Datroway could achieve a 56% peak share in the IO-ineligible population and that Trodelvy could achieve a 60% peak share in the PD-L1-positive cohort.
Datroway is currently in clinical development for the treatment of PD-L1-positive 1L TNBC, in combination with AstraZeneca’s in-house PD-L1 inhibitor, Imfinzi (atezolizumab), which to date has no approvals in breast cancer (this trial, TROPION-Breast05 is expected to read out by mid-2027). Both Datroway and Trodelvy are trialing in pre-metastatic TNBC, as well, with Datroway’s trial expecting to read out mid- 2027 and Trodelvy’s by the end of 2028.
What remains for this field is the promise of yet another TROP2 ADC, Merck’s sacituzumab tirumotecan (sac-TMT). In its phase 2 OptiTROP-Breast05 trial, Sac-TMT demonstrated improved response rates over its in-class competitors across the PD-L1 spectrum.
[1] Dent et al. 2026 (TROPION-Breast02)
Enhertu is poised to dominate first-line HER2+ breast cancer
Equinox Group’s analysis of the Enhertu + Perjeta combination in first-line HER2+ breast cancer predicts a peak-year patient share of 46% in that setting. Our finding is based on initial results from the Destiny-Breast09[1] trial and the expected competitive environment. FDA approval in first-line is likely by the end of 2025[2].
The core of our analysis compares the net clinical improvement of the Enhertu regimen vs. the current standard of care, Perjeta + Herceptin + paclitaxel. Using our rigorous, data-driven methodology, we find that the Enhertu regimen reduces medical need by 14.6%.
History shows that drugs with a 10% or greater reduction in need typically go on to dominate their segment. Enhertu’s improvement in this population is similar to Tagrisso’s advantage in first-line EGFR+ NSCLC.
The graphic quantifies that net clinical improvement, and shows the contribution of each clinical attribute. The biggest driver is efficacy, primarily progression-free survival (40.7 months for the Enhertu regimen vs. 26.9 months for the SOC). Because the median overall survival data is not yet mature, we have made a conservative assumption about that value for Enhertu. Moreover, the Enhertu regimen spares patients paclitaxel, greatly reducing the frequency of neutropenia and offering a cleaner side effect profile. While the Enhertu regimen costs more, that modest disadvantage is overwhelmed by the clinical benefits.
Enhertu: A New Leader in Later-Line Breast Cancer
Conclusion: Enhertu achieves an impressive clinical innovation score for its substantial efficacy improvements over the current SOC (trastuzumab + capecitabine) for adults with HER2+ metastatic breast cancer who have failed multiple prior therapies.
Enhertu (trastuzumab deruxtecan, Daiichi-Sankyo and AstraZeneca) was approved in December 2019 for HER2+ unresectable or metastatic breast cancer patients who have received multiple prior anti-HER2 treatments. It boasts a significant increase in progression-free survival compared to the current standard of care (SOC), trastuzumab + capecitabine (16.4 vs. 5.6 months), as well as a notable improvement in overall response rate (60.9% vs. 22.8%). While survival data is not yet mature, even the most conservative of estimates sees Enhertu winning the day for HER2+ patients eligible for a third or later line of treatment.
The waterfall chart below shows that Enhertu’s improvements in efficacy far outweigh its higher cost and slightly worse side effect profile when compared to the current SOC. The jump in efficacy, as well as its trickle-down effect on mortality and morbidity, deliver a strong clinical innovation score of 26%.
We expect Enhertu to dominate treatment in this setting within two years. Analysts’ estimates of peak sales around $2.5 billion are reasonable.