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)
Trodelvy: A New Option for Later Lines TNBC
Conclusion: Trodelvy offers moderate clinical innovation in relapsed/refractory triple-negative breast cancer (R/R TNBC), suggesting it will be prescribed to a large share of patients in this population. We compare the results with other recent launches in breast cancers.
In April 2020, the FDA granted accelerated approval to Trodelvy (sacituzumab govitecan-hziy, Gilead) in patients with metastatic TNBC who have failed two prior lines of therapy. Now, a year later, the FDA has granted full approval to Trodelvy for women with TNBC who have had received two or more systemic therapies, at least one for metastatic disease. Our analysis is based on phase III clinical data (NCT02574455).
TNBC makes up 15-20% of metastatic breast cancer incidence and remains an area of high unmet need. Patients at later lines have historically had few options—all of which offered short time to progression and poor survival rates.
Trodelvy boasts a significant increase in both median progression-free survival (mPFS) and median overall survival (mOS) when compared to physician’s choice chemotherapy. In the phase III ASCENT trial, Trodelvy patients without brain metastasis had an average PFS of 5.6 months, compared to 1.7 months for chemotherapy; mOS almost doubled, going from 6.7 months to 12.1. Trodelvy’s efficacy in patients with brain metastasis was only marginally less impressive. When modeled in Equinox’s framework, these results yield a Clinical Innovation score for Trodelvy of 9.3%, which is moderately differentiated (defined as 5-10% improvement), based on a large set of historical examples.
To put into context Trodelvy’s commercial outlook in R/R TNBC, we can compare it with other breast cancer therapies launched in recent years, regarding:
Sizes of the populations (bubble size)
Level of medical need (Y-axis)
Clinical improvement over the previous standard of care (Equinox Group’s “Clinical Innovation” metric, on the X-axis)
Green bubbles represent drugs with a clinical innovation score greater than 10% (highly innovative drugs)
Yellow bubbles represent drugs with a clinical innovation score of 5-10% (moderately innovative drugs)
Orange bubbles represent drugs with a clinical innovation score of less than 5% (low innovation drugs)
The level of unmet medical need in R/R TNBC treated with chemotherapy is extraordinarily high at 4.22 on Equinox Group’s 0-5 unmet need scoring system. Need is driven by the excess risk of mortality: 50 times higher than in an age-matched population.
Our analysis suggests Trodelvy will achieve good patient share in this small population. Its Clinical Innovation is only slightly lower than that achieved by Perjeta (in combination with trastuzumab + docetaxel) in 1st line HER2+ metastatic breast cancer – a regimen that dominates treatment in its population.
Enhertu in 3rd line HER2+ mBC addresses the second highest level of medical need among the indications here; it offers strong clinical innovation of 26%, suggesting it has strong patient share potential.
Trodelvy’s modest revenue of $72 million in Q1 2021 reflects its initial launches in small patient populations. In contrast, Ibrance is targeted to a much larger, lower-need population, offers high clinical innovation (15.7%) and has achieved a substantial patient share and sales ($5.4 billion in 2020). Kisqali’s more modest sales of $687 million in 2020 are explained by its lack of meaningful improvement vs. Ibrance and a launch that was two years later.
Trodelvy is in development in larger populations, including early lines of TNBC, HR+/HER 2- metastatic breast cancer and metastatic non-small-cell lung cancer. Its commercial outlook in those indications, including patient share and pricing potential, will depend on the level of Clinical Innovation it delivers.