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Luspatercept-Aamt for Anemia in Adults With MDS

The FDA approved luspatercept-aamt for the treatment of anemia failing an erythropoiesis-stimulating agent and requiring 2 or more red blood cell (RBC) units over 8 weeks in adult patients with very low-risk to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).

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Efficacy was demonstrated in the MEDALIST trial (NCT02631070), a randomized, multi-center, double-blind, placebo-controlled trial in 229 patients with IPSS-R very low, low, or intermediate-risk myelodysplastic syndromes who had ring sideroblasts and required RBC transfusions (2 or more RBC units over 8 weeks). Patients were randomized 2:1 to luspatercept-aamt or placebo. All patients received best supportive care, which included RBC transfusions.


The main efficacy endpoint in MDS-RS and MDS-RS-T was the proportion of patients who were RBC-transfusion independent (RBC-TI), defined as the absence of any RBC transfusion during any consecutive 8-week period between weeks 1 and 24.


Of the 153 patients who received luspatercept-aamt, 58 (37.9%, 95% CI: 30.2, 46.1) were RBC-TI for at least 8 weeks, compared to 10 patients (13.2%, 95% CI: 6.5, 22.9) who received placebo (treatment difference 24.6 percent [95% CI: 14.5, 34.6; p<0.0001]).


The most common (>10%) adverse reactions to luspatercept-aamt are fatigue, headache, musculoskeletal pain, arthralgia, dizziness/vertigo, nausea, diarrhea, cough, abdominal pain, dyspnea, and hypersensitivity.


The recommended starting dose of luspatercept-aamt is 1 mg/kg once every 3 weeks by subcutaneous injection. Review hemoglobin results prior to each administration.


Durvalumab for First-Line Treatment in Extensive-Stage Small Cell Lung Cancer

Durvalumab has been approved in the U.S. as a first-line treatment for adult patients with extensive-stage small cell lung cancer (ES-SCLC) in combination with standard-of-care (SoC) chemotherapies, etoposide and either carboplatin or cisplatin (platinum-etoposide).


The approval by the FDA was based on positive results from the phase III CASPIAN trial showing durvalumab in combination with SoC platinum-etoposide demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) versus SoC alone. SCLC is a highly aggressive, fast-growing form of lung cancer that typically recurs and progresses rapidly despite initial response to chemotherapy.


"Patients with extensive-stage small cell lung cancer continue to face a poor prognosis, and finding new medicines to improve outcomes in this setting has been a formidable challenge," noted Jonathan Goldman, MD, Associate Professor of Hematology & Oncology at UCLA Medical Center in Santa Monica and a lead investigator in the phase III CASPIAN trial. "The CASPIAN trial enables clinicians to choose durvalumab in combination with etoposide and either carboplatin or cisplatin, making this an important new first-line treatment option for patients that is both effective and well-tolerated."


The phase III CASPIAN trial had two primary endpoints comparing experimental arms to SoC. In the durvalumab plus SoC arm, the risk of death was reduced by 27 percent (equal to a hazard ratio of 0.73; 95% CI 0.59-0.91; p=0.0047), with median OS of 13.0 months versus 10.3 months for SoC alone. Results also showed an increased confirmed objective response rate in the durvalumab plus SoC arm (68% vs. 58% for SoC alone). The safety and tolerability for durvalumab plus SoC was consistent with the known safety profiles of these medicines. The durvalumab plus SoC data from the CASPIAN trial were published in The Lancet (2019;394(10212):1929-1939).


The second experimental arm testing tremelimumab added to durvalumab and SoC recently read out but did not meet the primary endpoint. Details will be presented at a forthcoming medical meeting.


The most common adverse reactions (>=20% of patients with extensive-stage SCLC) were nausea, fatigue/asthenia, and alopecia. The CASPIAN trial used a fixed dose of durvalumab (1,500 mg) administered every 3 weeks for 4 cycles while in combination with chemotherapy and then every 4 weeks until disease progression as a single medicine. As part of a broad development program, durvalumab is also being tested following concurrent chemoradiation therapy in patients with limited-stage SCLC in the phase III ADRIATIC trial with data anticipated in 2021.


Durvalumab received its first approval based on the phase III CASPIAN trial in Singapore for patients with ES-SCLC in February 2020. Durvalumab in combination with etoposide and either carboplatin or cisplatin is currently under regulatory review for the treatment of ES-SCLC in the first-line setting based on the phase III CASPIAN trial in the EU and Japan.


Request to Discuss Breakthrough Therapy Designation for Leronlimab

The FDA has received a request for a preliminary meeting to discuss new clinical data which may support an objective to obtain Breakthrough Therapy designation (BTD) for leronlimab in the treatment of metastatic triple-negative breast cancer (mTNBC).


The FDA had previously granted Fast Track designation to leronlimab for the treatment of mTNBC. The FDA recommended such a meeting to provide preliminary advice prior to resubmission of a Breakthrough Therapy designation request. Concurrent with the phase Ib/II trial for mTNBC and expanded access studies for MBC, it is also conducting a phase II trial with leronlimab for 22 solid cancer tumors.


As an aggressive histological subtype, mTNBC has a poor prognosis. In addition, metastatic breast cancer (MBC) is breast cancer that has spread beyond the breast and lymph nodes to other organs in the body (typically the bones, liver, lungs, or brain). Both types of cancer pose significant challenges for patients due to their aggressiveness and limited treatment options.


The phase Ib/II study involves monitoring of circulating tumor cells, epithelial mesenchymal transition in tumor metastasis, and cancer-associated microphage-like cells every 21 days during the treatment phase.


Digital Pathology Solution Available for Primary Diagnostics & Remote Reading

The FDA has provided a 510(k) clearance for the Sectra Digital Pathology Module that enables health care providers to use a digital pathology solution for primary diagnostics. The solution makes it possible to move towards fully integrated diagnostics, which is especially important in complex cancer cases.


The digital pathology solution is already used in the U.S. for research and tumor boards and can now also be used in primary diagnostics. With digital images of tissue samples instead of physical glass slides, pathologists gain instant access to current and historical images and related data, as well as to digital tools for reviewing the images. Digital access also facilitates efficient second opinions, remote reading, and specialist consultations, and makes integrated diagnostics possible.


The digital pathology solution allows health care providers to use a single solution for their medical imaging needs across all specialties, enabling integrated diagnostics. A deeper cooperation and ability to access other departmental images and information contributes to improved efficiency and patient care. This is especially important for complex cases where both radiology and pathology play key roles. Instant access to digital pathology images, side by side with radiology or other images, enables more efficient discussions and the ability to give detailed descriptions of findings.