AstraZenca’s Saruparib Shows Promise as First-in-Class PARP1-Selective Inhibitor in HRR-Deficient Breast Cancers: AACR 2024

At the American Association for Cancer Research (AACR) Annual Meeting 2024, significant findings from the Phase I/II PETRA trial, led by researchers at The University of Texas MD Anderson Cancer Center, were presented. The trial focused on evaluating the first-in-class PARP1-selective inhibitor, saruparib, in patients with homologous recombination repair (HRR)-deficient breast cancers.

Key Findings:

• Promising Efficacy: Saruparib demonstrated promising early efficacy, with an objective response rate of 48.8% and a median progression-free survival of 9.1 months among 31 patients with advanced breast cancers harboring HRR deficiency mutations.
• Favorable Safety Profile: The drug exhibited a favorable safety profile, with low rates of dose reduction (14.2%) and discontinuation (3.5%) due to treatment-related adverse events. Common adverse events included anemia, neutropenia, thrombocytopenia, fatigue, and asthenia.
• Selective Targeting: Saruparib is a new-generation PARP inhibitor selectively targeting PARP1, unlike previous inhibitors that targeted both PARP1 and PARP2. This selective targeting contributes to its improved safety profile and potential for combination therapies.
• Potential Clinical Impact: The improved safety profile of saruparib may enable more combinations with other treatments and extend the benefits of PARP inhibitors to patients in earlier disease stages.

Expert Insights: As the lead investigator, Dr. Yap highlighted saruparib’s wide therapeutic index and its potential to allow patients to remain on treatment longer at an optimal dose. He emphasized the significance of its favorable safety profile compared to approved first-generation PARP inhibitors, which opens doors for rational combination strategies and further clinical evaluation, including in Phase III trials.

Conclusion: The PETRA trial’s findings underscore saruparib’s potential as a promising therapeutic option for patients with HRR-deficient breast cancers. Its encouraging efficacy, favorable safety profile, and selective targeting of PARP1 represent significant advancements in the field of precision oncology. Moving forward, ongoing research and clinical trials will continue to explore saruparib’s role in improving outcomes for patients with breast cancer and potentially other malignancies characterized by DNA repair deficiencies.

For more information,refer DelveInsight’s report:

PARP Inhibitors Market Size, Target Population, Competitive Landscape & Market Forecast – 2034