Trodelvy and Keytruda Show Significant Progression-Free Survival in Untreated PD-L1+ Metastatic Triple-Negative Breast Cancer

Gilead Sciences has announced promising results from their latest clinical trial, the Phase 3 ASCENT-04/KEYNOTE-D19 study. This research involved the combination of Trodelvy, an antibody-drug conjugate, with Keytruda, an immuno-oncology agent, in treating patients with a specific type of breast cancer known as triple-negative breast cancer (mTNBC), which is both challenging and aggressive. The study demonstrated that this combination markedly improved progression-free survival (PFS) compared to the standard treatment of Keytruda with chemotherapy for patients with inoperable or metastatic mTNBC expressing PD-L1 (CPS ≥10).

The trial's findings offer new hope for those battling this severe cancer form, as it is the first to show the potential of merging an antibody-drug conjugate with an immuno-oncology agent in early treatment phases. Dr. Dietmar Berger, Gilead Sciences’ Chief Medical Officer, highlighted the groundbreaking nature of these results, suggesting they could redefine treatment paths for such patients. Similarly, Dr. Sara Tolaney from the Dana-Farber Cancer Institute emphasized the critical need for more effective treatment options, noting that this study could lead to a new approach by combining the strengths of a potent antibody-drug conjugate and immunotherapy.

Despite not having reached maturity in the analysis of overall survival (OS), there is already an early indication of improvement in OS when using Trodelvy with Keytruda. Gilead plans to continue monitoring these outcomes with further patient follow-ups and additional analyses. Detailed results are expected to be shared at an upcoming medical conference and during discussions with regulatory bodies. It is important to note that the use of Trodelvy plus Keytruda in patients with PD-L1+ metastatic TNBC remains investigational, and its safety and efficacy in this context are yet to be confirmed.

Trodelvy stands out in the realm of breast cancer treatments as the sole approved Trop-2-directed antibody-drug conjugate, having shown significant survival benefits in different types of metastatic breast cancers. It is recommended by the National Comprehensive Cancer Network Guidelines as a preferred treatment and carries a high rating on the ESMO Magnitude of Clinical Benefit Scale for its efficacy in mTNBC.

With over 50,000 patients treated globally, Trodelvy has demonstrated consistent results across various clinical trials and real-world settings. Gilead is currently running three Phase 3 studies examining Trodelvy's effectiveness across different breast cancer types, including the upcoming ASCENT-03 and ASCENT-05 trials. Trodelvy is also being explored for additional cancers such as lung and gynecological cancers, showing potential versatility in cancer treatment.

Triple-negative breast cancer (TNBC) is particularly aggressive, contributing to approximately 15% of all breast cancer cases. This type often affects younger, premenopausal women and is more common among Black and Hispanic women. The aggressive nature of TNBC results in limited treatment options and a poorer prognosis compared to other breast cancer types. The five-year survival rate for those with metastatic TNBC is notably low at 12%, underscoring the urgent need for more effective treatments.

Gilead's collaboration with Merck & Co. facilitated this groundbreaking research, aiming to enhance treatment outcomes for patients with this challenging cancer type. The ASCENT-04/KEYNOTE-D19 trial enrolled 443 patients, evaluating the efficacy and safety of the Trodelvy and Keytruda combination versus standard chemotherapy and Keytruda. The study's primary goal was to assess progression-free survival, with secondary goals including overall survival and response rates, among others.

Trodelvy is recognized as a first-in-class Trop-2-directed antibody-drug conjugate, known for its ability to target cells with high Trop-2 expression, including many breast and lung cancers. It is approved for use in multiple countries for specific breast cancer patient groups and continues to be investigated for broader applications in various cancer types.