Neil Vasan, Director of Breast Cancer Translational Research at NYU Langone Health, shared a post on X:
My take: the post-DB09 interest in induction → maintenance strategies—aimed at balancing toxicity mitigation with maximal efficacy—deserves careful scrutiny, and the assumptions behind it aren’t yet established.
Title: Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast Cancer
Authors: Sara M. Tolaney, Zefei Jiang, Qingyuan Zhang, Romualdo Barroso-Sousa, Yeon Hee Park, Mothaffar F. Rimawi, Cristina Saura, Andreas Schneeweiss, Masakazu Toi, Yee Soo Chae, Yasemin Kemal, Mukesh Chaudhari, Mehmet A.N. Şendur, Toshinari Yamashita, Monica Casalnuovo, Michael A. Danso, Jie Liu, Jagdish Shetty, Pia Herbolsheimer, Sibylle Loibl
Read the Full Article in NEJM.
DESTINY-Breast09 tested continuous T-DXd plus pertuzumab until progression or toxicity. It did not test a planned induction phase followed by HP maintenance.
The 40.7-month median PFS observed in DB09 reflects ongoing T-DXd+P exposure. Applying that result to a redesigned regimen requires caution.
In DB09, T-DXd + pertuzumab performed better than T-DXd monotherapy, with higher ORR and CR rates, suggesting dual HER2 blockade contributes meaningfully to benefit.
If durability in DB09 depends on sustained ADC pressure plus pertuzumab, early de-escalation could plausibly reduce the depth or durability of response.
There’s also a potential trade-off scenario: patients incur ADC-related toxicity, yet may not remain on therapy long enough to capture the full benefit seen with continuous treatment.
This question may be most consequential in high-burden visceral disease or CNS-risk settings, where depth and durability of control matter most.
It’s also quite atypical in oncology to substantially redesign regimens derived from phase 3 registrational trials without prospective data supporting the change. I can’t think of any prominent example (someone correct me if I’m wrong) apart from modifying the dosing (e.g. FOLFIRINOX, BOLERO-2).
DEMETHER is often referenced, but it will not address whether T-DXd + pertuzumab is an effective induction strategy, since it does not test fixed-course T-DXd+P followed by HP maintenance.
Title: Abstract P5-03-11: DEMETHER: A single-arm phase II trial to evaluate the efficacy & safety of subcutaneous pertuzumab and trastuzumab maintenance after induction treatment w/ trastuzumab deruxtecan (T-DXd) for previously untreated HER2-positive advanced breast cancer
Authors: Javier Cortés, Juan José García-Mosquera, Gabriele Antonarelli, Alessandra Gennari, Carlos Barrios, Giuseppe Curigliano, Hope Rugo, Joseph Gligorov, Nadia Harbeck, Sara M. Tolaney, William J. Gradishar, Peter Schmid, María Gion, Rui Rui Zhan, Emilia Szosta, Paula González-Alonso, Michela Verbeni, José Manuel Pérez-García, Antonio Llombart-Cussac
Read the Full Article in Clinical Cancer Research.
Induction → maintenance may ultimately prove reasonable, but DB09 itself supports continuous T-DXd plus pertuzumab, and alternative strategies remain hypotheses requiring formal testing.
More posts featuring Neil Vasan.