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Phase III Trial of Pirtobrutinib Versus Idelalisib/Rituximab or Bendamustine/Rituximab in Covalent Bruton Tyrosine Kinase Inhibitor–Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-321)

Pirtobrutinib improved progression-free survival (PFS) to 14 months compared to 8 months with Idelalisib/Rituximab or Bendamustine/Rituximab (IdelaR/BR), with a hazard ratio of 0.54, in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had previously been treated with covalent BTK inhibitors (cBTKi). It also demonstrated favorable tolerability. With acalabrutinib and venetoclax emerging as preferred first-line therapies, Pirtobrutinib represents a strong second-line option for eligible patients.

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Pasritamig, a First-in-Class, Bispecific T-Cell Engager Targeting Human Kallikrein 2, in Metastatic Castration-Resistant Prostate Cancer: A Phase I Study

Pasritamig was administered to patients who had received a median of four prior lines of systemic therapy. It was well tolerated, with manageable adverse events, making it suitable for outpatient administration. The treatment showed a median radiographic progression-free survival of 7.85 months, and 14 out of 33 participants achieved a ≥50% reduction in baseline PSA levels. So, stay tuned.

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Adagrasib versus docetaxel in KRASG12C-mutated non-small-cell lung cancer (KRYSTAL-12): a randomised, open-label, phase 3 trial

Adagrasib demonstrated a median progression-free survival (PFS) of 5.5 months compared to 3.8 months with docetaxel in patients with KRAS G12C-mutated tumors. Treatment-related adverse events occurred in 47% of patients receiving Adagrasib and 46% in the docetaxel group. In my experience, Adagrasib is also more tolerable, making it a favorable option for this patient population.

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Lisocabtagene Maraleucel Versus Standard of Care for Second-Line Relapsed/Refractory Large B-Cell Lymphoma: 3-Year Follow-Up From the Randomized, Phase III TRANSFORM Study

CAR-T therapy outperformed standard of care (SOC) as a second-line treatment, with progression-free survival (PFS) not reached in the CAR-T group compared to 6.2 months in the SOC group. Despite two-thirds of patients crossing over, CAR-T still demonstrated a three-year overall survival rate of 63%, versus 52% with SOC. These are impressive and durable results. The SOC regimen consisted of three cycles of chemoimmunotherapy followed by high-dose chemotherapy and autologous stem cell transplant. This positions CAR-T as a viable second-line option for eligible patients.

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Vepdegestrant, a PROTAC Estrogen Receptor Degrader, in Advanced Breast Cancer

Vepdegestrant is an oral proteolysis-targeting chimera (PROTAC) estrogen receptor (ER) degrader that directly utilizes the ubiquitin–proteasome system. It was compared to fulvestrant in patients who had received one prior line of hormonal therapy with a CDK4/6 inhibitor. Among patients with ESR1 mutations, Vepdegestrant demonstrated a median progression-free survival (PFS) of 5.0 months versus 2.1 months with fulvestrant. In the overall population, the median PFS was 3.8 months for Vepdegestrant and 3.6 months for fulvestrant, indicating that the drug showed particular efficacy in tumors harboring ESR1 mutations.

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Adjuvant Cemiplimab or Placebo in High-Risk Cutaneous Squamous-Cell Carcinoma

Cemiplimab significantly reduced recurrence in patients with high-risk disease following surgery and radiation, with a two-year disease-free survival (DFS) rate of 87.1% compared to 64.1% in the control group. These patients included those with nodal involvement, T4 tumors, perineural invasion, or locally recurrent disease. However, nearly 10% of patients still discontinued therapy.

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Elinzanetant for Vasomotor Symptoms from Endocrine Therapy for Breast Cancer

Elinzanitant, a neurokinin-targeted therapy, has been shown to reduce vasomotor symptoms compared to placebo. These symptoms are one of the reasons some of my patients discontinue aromatase inhibitor (AI) therapy, so Elinzanitant presents a promising alternative to help manage these side effects. Additionally, Fezolinetant is already approved and available on the market.

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