Articles related to TARGETED THERAPIES

Recent studies identify DNA damage repair (DDR) genes as a new class of endocrine therapy resistance driver that contributes to poor survival among ER+ breast cancer patients. This study reveals differences in DDR regulation in Black women that may in part contribute to the higher breast cancer mortality in Black women vs. other populations. Based on their findings, the authors recommend more effort to refine biomarker profiles to ensure precision medicine for underserved populations.

In a randomized clinical trial of 128 patients with refractory mCRC, the addition of the PD-L1 inhibitor atezolizumab to capecitabine and bevacizumab therapy resulted in marginally longer PFS vs the placebo comparator arm. However, the median improvement — 4.4 vs 3.6 months – was deemed not clinically relevant.

PIK3CA is the most mutated oncogene across many of the common solid tumor types. Consequently, targeting PIK3CA has been of major clinical interest. Initial efforts at have not been promising, however. The limiting factors have primarily been lack of isoform specificity of inhibitors and dose-limiting toxicities. This study evaluates copanlisib, an α and δ isoform–specific phosphoinositide 3-kinase (PI3K) inhibitor, in patients with PIK3CA mutations.

Interest in immune-modulating neoadjuvant therapy for melanoma is growing. It is possible that BRAF/MEK inhibition will be more effective in the neoadjuvant than in the adjuvant setting because of the effect of the tumor biomass. And the benefits neoadjuvant therapy would offer in assessing biologic response assessment to treatment are significant. In this review the authors discuss the rationale for this treatment approach, summarize completed and ongoing neoadjuvant clinical trials, and contextualize these findings within the growing body of knowledge about targeted and immune checkpoint therapy.

Extending the ELEVATE-TN to four additional years (beyond the two-year follow-up in the pivotal trial) showed ongoing efficacy with no new safety signals. Additionally, the four year ELEVATE-RR trial comparing acalabrutinib with ibrutinib as monotherapy in high-risk populations showed overall non-inferiority of acalabrutinib and a lower rate of several adverse events, including atrial fibrillation.

Dana Farber’s CLL Center associate director Matthew S. Davids, MD, MMSc highlights some of his key takeaways from the recent ASH meeting: Novel treatment approaches in chronic lymphocytic leukemia (CLL), including large phase 3 studies, some smaller studies combining novel drugs, and long-term follow-ups of prior phase 3 studies; three reports with practice-changing implications; and a surprising finding in the ECOG 1912 study, which demonstrated an overall survival benefit for patients who received ibrutinib with rituximab.