Articles related to TARGETED THERAPIES

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.

This update of the GO29365 study shows significant survival benefit with pola + BR vs BR alone in R/R, transplant ineligible DLBCL. In the randomization arms, median progression-free survival was 9.2 vs 3.7 months and median overall survival was 12.4 vs 4.7 months for the pola + BR arm vs the BR arm. In the extension cohort, the OR rate was 41.5%, and the CR rate was 38.7%; PFS and OS were 6.6 months and 12.5 months, respectively.

Presented at SABCS 2021, the EMERALD Study of elacastrant and the PHOEBE Trial of pyrotinib showed a better than doubling of 12-month PFS with the first agent, and an improvement in both OS and PFT with the second agent. And the results of the DESTINY-Breast03 study have been called “practice changing.”