Pyrotinib

Datopotamab Deruxtecan's Role in HR+/HER2- Breast Cancer Treatment: Sequencing and Safety Considerations

4 months ago

• Datopotamab deruxtecan (Dato-DXd) is poised to become a standard treatment for metastatic hormone receptor-positive, HER2-negative breast cancer after prior systemic therapy. • Optimal sequencing of antibody-drug conjugates (ADCs) like Dato-DXd, sacituzumab govitecan, and trastuzumab deruxtecan remains uncertain, especially considering overlapping toxicities. • Real-world toxicity profiles suggest sacituzumab govitecan may cause more cytopenias and diarrhea, while Dato-DXd and trastuzumab deruxtecan are linked to interstitial lung disease. • The lack of overall survival difference in the TROPION-Breast01 trial raises questions about efficacy issues or the impact of crossover between treatment arms.

T-DM1 Shows Sustained Survival Benefit in HER2-Positive Breast Cancer

4 months ago

• Adjuvant trastuzumab emtansine (T-DM1) demonstrates significantly improved overall survival compared to trastuzumab in HER2-positive early breast cancer patients with residual invasive disease. • The KATHERINE trial's long-term follow-up reveals a sustained benefit in invasive disease-free survival with T-DM1, reducing the risk of recurrence or death. • T-DM1's consistent benefit across patient subgroups, regardless of disease extent or hormone receptor status, reinforces its role as a standard of care. • While adverse events were more frequent with T-DM1, the overall safety profile remains acceptable, supporting its use in high-risk HER2-positive breast cancer.

ARX788 Demonstrates Significant PFS Benefit in HER2-Positive Breast Cancer

4 months ago

• A phase III trial of ARX788 showed a significantly longer median progression-free survival (PFS) of 11.3 months compared to 8.2 months with lapatinib plus capecitabine (LC) in HER2-positive advanced breast cancer patients. • The objective response rate (ORR) was higher in the ARX788 group (63.8%) compared to the LC group (52.7%), with a significantly longer duration of response (DoR) of 12.5 months versus 8.3 months. • ARX788 demonstrated a manageable safety profile, with the most frequent treatment-related adverse events (TRAEs) including hepatic enzyme increase, dry eye, blurred vision, alopecia, and interstitial lung disease (ILD). • The study suggests ARX788 could be an alternative second-line treatment option for HER2-positive advanced breast cancer patients who have progressed on trastuzumab and taxane.

HER2-Targeted Therapies Evolve in NSCLC Treatment Landscape

4 months ago

• Fam-trastuzumab deruxtecan-nxki (T-DXd) is currently the only FDA-approved therapy for HER2-mutated NSCLC post-chemotherapy, making platinum-based chemotherapy the preferred first-line treatment. • Zongertinib, a mutant-selective HER2 inhibitor, has demonstrated promising efficacy and manageable toxicity in early trials, leading to ongoing phase 3 studies in the first-line setting. • BAY 2927088, an oral TKI, showed significant objective response rates and progression-free survival in patients with HER2-mutated NSCLC, particularly those with HER2 YVMA insertions. • Clinical trials are actively exploring the optimal sequencing of HER2-targeted therapies and their potential in the first-line treatment of HER2-mutated NSCLC.

Enhertu Approved for HER2-Low and HER2-Ultralow Metastatic Breast Cancer

5 months ago

• The FDA has approved Enhertu for HR-positive, HER2-low or HER2-ultralow metastatic breast cancer after endocrine therapy progression. • DESTINY-Breast06 trial data showed a 36% reduction in disease progression or death risk compared to chemotherapy. • Patients on Enhertu had a median progression-free survival of 13.2 months versus 8.1 months on chemotherapy. • This approval expands Enhertu's use to an earlier treatment setting and a broader patient population.

Targeted Therapies Reshape Treatment Strategies for Mutation-Driven Cancers

5 months ago

• Oral targeted therapies are significantly improving the patient experience by directly addressing actionable mutations, leading to more personalized treatment plans. • The INAVO120 trial's efficacy and safety data have paved the way for the approval of inavolisib, a PI3Kα-specific inhibitor, offering a more targeted approach. • Precision medicine is driving the exploration of targeted therapy combinations in earlier lines of treatment, as demonstrated by trials like ELEVATE and CAPItello-292. • Emerging strategies focus on targeting truncal mutations earlier in treatment to potentially improve outcomes and address the evolving landscape of cancer therapy.

Advancements in Breast Cancer Research Unveiled at SABCS 2024

5 months ago

• The PATINA trial suggests palbociclib with anti-HER2 and endocrine therapy may become a new standard for HR+, HER2+ metastatic breast cancer. • COMET trial indicates active monitoring is comparable to surgery for low-risk DCIS, offering a potential alternative management option. • OlympiA trial's long-term results reinforce olaparib's role in preventing recurrence and highlight the importance of BRCA testing for early-stage breast cancer.

SHR-A1811 Demonstrates Promising Activity in HER2-Expressing Breast Cancer Subtypes

5 months ago

• SHR-A1811, a novel anti-HER2 ADC, shows promising anti-tumor activity and acceptable safety in HR-positive/HER2-low breast cancer in a phase 2 trial. • In HR-positive/HER2-low breast cancer, SHR-A1811 achieved an objective response rate of 74.3% in the first stage of a phase 2 trial. • The FASCINATE-N trial showed SHR-A1811 monotherapy had similar pathological complete response rates compared to standard chemotherapy in HER2-positive breast cancer. • Common treatment-related adverse events with SHR-A1811 include neutropenia, leukopenia, anemia, nausea, asthenia, and vomiting, with manageable safety profiles.

Genomic Profiling of HER2-Low Metastatic Breast Cancer Reveals Potential Therapeutic Strategies

5 months ago

• Analysis of circulating tumor DNA (ctDNA) in HER2-low metastatic breast cancer (MBC) identifies frequent mutations in TP53, PIK3CA, and ESR1. • HER2-low MBC exhibits distinct mutation profiles compared to HER2-0 and HER2-positive MBC, with differences in genes like ERBB2, AKT1, and ESR1. • HER2-low MBC patients with ERBB2 mutations may benefit from HER2-TKI treatment, while those with metabolic pathway-related gene mutations show improved outcomes with chemotherapy and endocrine therapy. • Molecular clustering of HER2-low MBC reveals distinct subgroups with varying mutation frequencies in RTK–RAS, PI3K, ERBB2, and metabolic pathways, suggesting potential for tailored therapies.

Disitamab Vedotin Shows Promising Activity in HER2-Expressing Metastatic Breast Cancer with PAM Pathway Abnormalities

6 months ago

• Disitamab vedotin (RC48) demonstrates an objective response rate of 34.4% in HER2-expressing metastatic breast cancer patients with abnormal PAM pathway activation. • The disease control rate with disitamab vedotin was 81.97% across all HER2-expressing metastatic breast cancer patients in the phase 2 trial. • Median progression-free survival was 3.5 months in all patients, with no significant difference between HER2-positive and HER2-low subgroups. • The safety profile of disitamab vedotin was manageable, with most adverse events being grade 1 or 2, and no treatment-related deaths reported.

SHR-A1811 Plus Pyrotinib Shows Promising Efficacy in HER2-Positive Breast Cancer

7 months ago

• Neoadjuvant SHR-A1811, a novel anti-HER2 ADC, combined with pyrotinib, demonstrated significant antitumor activity in HER2-positive breast cancer patients. • The MUKDEN 07 trial reported a total pathologic complete response (tpCR) rate of 78.6% across all evaluable patients, indicating strong initial efficacy. • The combination therapy showed a manageable toxicity profile, with common adverse effects including diarrhea, anemia, and neutropenia, but manageable. • These findings suggest SHR-A1811 plus pyrotinib could be a promising neoadjuvant treatment option for HER2-positive breast cancer, warranting further investigation.

Pyrotinib Plus Metronomic Vinorelbine Shows Efficacy in HER2+ Advanced Breast Cancer Post-Trastuzumab

9 months ago

• A phase 2 trial in China demonstrated that pyrotinib combined with metronomic vinorelbine is effective in HER2-positive advanced breast cancer patients after trastuzumab failure. • The combination therapy achieved a median progression-free survival of 13.5 months and an overall response rate of 38.9% in the studied patient population. • The treatment regimen showed a manageable safety profile, with the most common adverse events being diarrhea, nausea, and vomiting, and no grade 4/5 events reported. • Researchers suggest this dual-oral regimen is a feasible option where antibody-drug conjugates are not readily accessible, warranting further investigation in larger trials.

Margetuximab Shows Promise as Alternative Therapy in HER2-Positive Advanced Breast Cancer

2 years ago

• Margetuximab, a second-generation anti-HER2 antibody, has shown potential as a later-line therapy for HER2-positive advanced breast cancer. • The SOPHIA trial demonstrated that margetuximab plus chemotherapy improved progression-free survival compared to trastuzumab plus chemotherapy, though overall survival was not significantly different. • Margetuximab's Fc-engineered design enhances antibody-dependent cell-mediated cytotoxicity, potentially benefiting patients with specific CD16A variants. • Ongoing trials, including SOPHIA CHINA and MARGOT, aim to further evaluate margetuximab's efficacy and identify patient populations that may benefit most.

Drug Development Updates