Beta-HCG Secretion by a Pulmonary Choriocarcinoma in a Male Patient.

Background: Paraneoplastic secretion of beta-subunit of human chorionic gonadotropin (ß-HCG) in pulmonary carcinoma is rare. Case Presentation. A 65-year-old man presented with bilateral gynaecomastia with abnormally high levels of ß-hCG and elevated oestradiol, progesterone, and testosterone levels on April 7, 2023. After excluding testicular malignancy, CT scan of the chest and abdomen revealed bilateral pulmonary lesions. Transthoracic biopsy confirmed malignancy with choriocarcinoma. MRI of the brain showed a solitary brain metastasis, while on a subsequent 18F-FDG PET/CT, no other metastatic lesions were seen. The patient was treated with chemoimmunotherapy carboplatin-etoposide-pembrolizumab with good partial response. Conclusion: Our case of a presumably stage IV dedifferentiated mNSCLC presenting as an extragonadal ß-hCG secreting pulmonary choriocarcinoma is a very rare tumor with a poor prognosis. Its biology, origin, and treatment remain to be elucidated. Cancer genome sequencing is necessary for the identification of the origin and seeking treatment.

Paclitaxel plus carboplatin and durvalumab with or without oleclumab for women with previously untreated locally advanced or metastatic triple-negative breast cancer: the randomized SYNERGY phase I/II trial.

Chemo-immunotherapy is the first-line standard of care for patients with PD-L1 positive metastatic triple-negative breast cancer (mTNBC). SYNERGY (NCT03616886) is a dose-finding phase I and a randomized phase II, open-label trial evaluating if targeting the immunosuppressive adenosine pathway can enhance the antitumor activity of chemo-immunotherapy. The phase I part included 6 patients with untreated locally-advanced or mTNBC to determine the safety and recommended phase II dose of the anti-CD73 antibody oleclumab in combination with the anti-PD-L1 durvalumab and 12 cycles of weekly carboplatin and paclitaxel. In the phase II part, 127 women were randomized 1:1 to receive chemo-immunotherapy, with (arm A) or without (arm B) oleclumab. The primary endpoint was the clinical benefit rate at week 24, defined as stable disease, partial or complete response per RECIST v1.1. Secondary endpoints included objective response rate, duration of response, survival outcomes (progression-free survival and overall survival), and safety. The trial did not meet its primary endpoint, as the 24-week clinical benefit rate was not significantly improved by adding oleclumab (43% vs. 44%, p = 0.61). Exploratory median progression-free survival was 5.9 months in arm A as compared to 7.0 months in arm B (p = 0.90). The safety profile was manageable in both arms.

Subcutaneous trastuzumab (Herceptin) versus intravenous trastuzumab for the treatment of patients with HER2-positive breast cancer: A time, motion and cost assessment study in a lean operating day care oncology unit.

OBJECTIVE: The subcutaneous (SC) formulation of trastuzumab represents an alternative to the intravenous (IV) infusion in the treatment of patients with HER2-positive metastatic and early breast cancer. We compared the two formulations in terms of time and cost differential. STUDY DESING: We conducted a time, motion and cost assessment study in a lean operating day care oncology unit to determine and compare the time and costs of trastuzumab SC versus IV administration in patients with HER2-positive breast cancer. Outcomes were the mean costs and the mean dedicated time of the health care professional (HCP) and patient chair time. Direct observation methodology was applied to collect data and statistical analysis was performed. RESULTS: The total preparation and administration time for trastuzumab IV was 4.07 times longer than the total time required for the trastuzumab SC administration. The total patient time spent in the day care oncology unit (in minutes) was 71% shorter with using SC administration. IV administration costs € 50.4 ($54,89) more in HCP time and consumable supplies and €162.53 ($177.00) of drug wastage. SC administration was associated with a total time saving of 53.7min for the HCPs and 122.5min for the patients. The administration of trastuzumab SC was translated in a cost saving of €212.93 ($231.73) per patient episode compared to trastuzumab IV, which could lead to a total potential saving of €3,832.74 ($4,171.06) over a full course of treatment (18 cycles) CONCLUSION: SC administration of trastuzumab was associated with a substantial reduction in active HCP time, patient chair time, unit time, and overall cost. These time and cost could be used to increase capacity within existing resources in a lean operating day dare oncology unit.

Management of pulmonary toxicity associated with targeted anticancer therapies.

INTRODUCTION: Targeted anticancer therapies act by interfering with defined molecular entities and/or biologic pathways. Because of their more specific mechanism of action, adverse events (AEs) on healthy tissues are intended to be minimal, resulting in a different toxicity profile from that observed with conventional cytotoxic chemotherapy. Pulmonary AEs are rare but potentially life-threatening and it is, therefore, critical to recognize early on and manage appropriately. AREAS COVERED: In this review, we aim to offer an overview of both more frequent and rare pulmonary AEs caused by targeted anticancer therapies and discuss possible treatment algorithms. Anti-vascular endothelial growth factor, anti-human epidermal growth factor receptor and anti-CD20 therapy will be reviewed, as well as immune checkpoint inhibitors, anaplastic lymphoma kinase inhibitors and mammalian target of rapamycin inhibitors. EXPERT OPINION: Novel agents used in the treatment of cancer have specific side-effects, the result of allergic reactions, on-target and off-target effects. Clinical syndromes associated with pulmonary toxicity vary from bronchospasms, hypersensitivity reactions, pneumonitis, acute respiratory distress, lung bleeding, pleural effusion to pneumothorax. Knowledge of risk factors, a high index of suspicion and a complete diagnostic work-up are essential for limiting the risk of these events becoming life threatening. The development of treatment algorithms is extremely helpful in managing these events. It is probable that these toxicities will be even more frequent with the introduction of combination therapies with the obvious challenge of discerning the responsible agent.

Trastuzumab emtansine in advanced human epidermal growth factor receptor 2-positive breast cancer.

INTRODUCTION: Ado- trastuzumab emtansine (T-DM1) is a human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate composed of trastuzumab, a stable linker (MCC), and the cytotoxic agent DM1 (derivative of maytansine; mertansine). T-DM1 retains the mechanisms of action of trastuzumab, but also acts as a, selectively delivered, tubulin inhibitor. Following antigen-mediated binding to the tumor cell, T-DM1 is endocytosed and intracellularly catabolized resulting in the release of its cytotoxic moiety. AREAS COVERED: T-DM1 has completed Phase III development and compared favorably with the lapatinib/capecitabine combination with a superior response rate (objective response rate [ORR]) and duration of response, longer duration of disease control (progression-free survival [PFS]), prolonged overall survival and improved tolerability and quality of life in patients with prior treatment with trastuzumab and a taxane. In a separate Phase III, T-DM1 was compared with any other chosen regimen in patients who had at least received two prior HER2-directed therapies. T-DM1 nearly doubled PFS. EXPERT OPINION: T-DM1 (Kadcyla) has become the treatment of choice in second-line and beyond for patients with advanced HER2-expressing breast cancer.