Pyrotinib

SHR-A1811, a third-gen ADC, showed comparable pathologic complete response (pCR) rates to standard PCbHP in HER2+ breast cancer patients in the FASCINATE-N trial. pCR rates were 63.2% in SHR-A1811 arm, 62.5% in SHR-A1811 plus pyrotinib arm, and 64.4% in PCbHP arm. No significant difference in pCR rates among the groups was observed. Grade 3-4 treatment-related adverse events were 44.8% in SHR-A1811 arm, 71.6% in combination arm, and 38.8% in PCbHP arm.

The phase 2 FASCINATE-N trial evaluated SHR-A1811, a novel ADC, in HER2-positive breast cancer, showing promising efficacy and tolerability. Patients were randomized to SHR-A1811, SHR-A1811 plus pyrotinib, or PCbHP. pCR rates were 63.2%, 62.5%, and 64.4% respectively, with no significant difference. SHR-A1811 may serve as a backbone for future treatments.

SHR-A1811, a third-gen ADC, showed promising antitumor activity in HER2-positive breast cancer patients in the phase 2 FASCINATE-N trial. Compared with standard 4-drug regimen, SHR-A1811, SHR-A1811 plus pyrotinib, and PCbHP had similar pCR rates of 63.2%, 62.5%, and 64.4% respectively. HR-negative patients had higher pCR rates. Grade 3-4 TRAEs varied across arms, with SHR-A1811 potentially serving as a backbone for future treatments.

Study of 1071 MBC patients (24.9% HER2-0, 45.6% HER2-low, 29.5% HER2-positive) reveals HER2-low MBC has higher HR positivity (73.6%) and lower TNBC subtype incidence. HER2-low MBC shows predominant missense mutations in TP53, PIK3CA, and ESR1, with potential benefits from PI3K, PARP, and AKT inhibitors. HER2-low MBC exhibits distinct mutation profiles compared to HER2-0 and HER2-positive groups, with significant differences in ERBB2 and AKT1 mutation frequencies. HER2-low MBC patients with ERBB2 mutations show better response to HER2-TKI treatment. HER2-low MBC with metabolic pathway-related gene mutations have higher DCR and longer PFS compared to HER2-0 MBC. Three molecular clusters identified in HER2-low MBC suggest heterogeneity and potential targeted therapy strategies.

Disitamab vedotin (RC48) showed efficacy with manageable safety in HER2-positive and HER2-low metastatic breast cancer with PAM pathway activation, with ORR of 34.40% and DCR of 81.97% in all patients. No significant PFS difference was observed between HER2-positive and HER2-low subgroups.

Lung cancer, primarily non-small cell lung cancer (NSCLC), is a leading cause of morbidity and mortality globally. Targeted therapies have emerged as a preferred first-line treatment for NSCLC patients with oncogenic driver mutations, such as EGFR, ALK, ROS1, BRAF, MET, RET, FGFR, and NTRK. These therapies, including small-molecule drugs and monoclonal antibodies, have shown superior efficacy compared to traditional chemotherapy and immunotherapy, particularly in specific molecular subtypes. Challenges remain in drug resistance, adverse effects, and determining optimal treatment sequences. Continued research is essential for advancing precision medicine in lung cancer treatment.

Neoadjuvant SHR-A1811 + pyrotinib in HER2-positive breast cancer showed 78.6% tpCR and 89.3% RCB 0/1 in MUKDEN 07 trial, with manageable toxicity.

OBiS Insights pre-meeting ESMO24 report profiles 275 new, unapproved cancer drugs, classified as 40% antibody-based, 37% small molecule, and 23% mixed bag. The report excludes drugs not in abstract titles and will update during the conference. 43% of these drugs were discussed at recent ASCO24 meetings.

Pyrotinib plus metronomic vinorelbine showed safety and efficacy in HER2+ advanced breast cancer post-trastuzumab, with median PFS of 13.5 months and ORR of 38.9%. The study highlights the need for alternative therapies due to economic constraints on ADCs. Subgroup analysis revealed better PFS in patients with lung metastases and primary trastuzumab resistance. No new AEs were reported, and the regimen warrants further study.

Article references discuss various aspects of breast cancer management, including global statistics, neoadjuvant chemotherapy, imaging biomarkers, AI applications, and predictive models for treatment response.