Cancer cachexia as a determinant of efficacy of first-line pembrolizumab in patients with advanced non-small cell lung cancer.

Pembrolizumab, either as a type of monotherapy or in combination with cytotoxic anticancer agents, is effective in the treatment of advanced non-small cell lung cancer (NSCLC). However, the development of cancer cachexia may adversely affect anticancer drug therapy. The present study investigated the effect of cancer cachexia on clinical outcomes in patients with advanced NSCLC who received first-line pembrolizumab. The data of patients with advanced NSCLC receiving first-line monotherapy or combination therapy with pembrolizumab were retrospectively analyzed. The primary endpoint was time to treatment failure (TTF), and the secondary endpoints were overall survival (OS) and incidence of adverse events (AEs). Clinical outcome was compared between patients with and without cancer cachexia. A total of 53 patients were analyzed. Among all patients, median TTF and OS were significantly shorter in patients with cancer cachexia than in those without [TTF: 5.8 vs. 10 months; hazard ratio (HR): 2.13; 95% confidence interval (CI): 1.07-4.24; P=0.016; OS: 12.1 months vs. not reached; HR: 5.85; 95% CI: 2.0-17.1; P=0.001]. In addition, TTF in the pembrolizumab monotherapy group was significantly shorter in patients with cancer cachexia than in those without, but no significant difference was detected in patients receiving pembrolizumab combination therapy. The incidence of AEs did not significantly differ between patients with and without cancer cachexia, except with regard to hypothyroidism. In conclusion, although cancer cachexia is prognostic of a poor outcome in patients with advanced NSCLC who receive first-line pembrolizumab, cancer cachexia might not affect therapeutic efficacy in combination therapy with pembrolizumab and cytotoxic anticancer agents.

Low-Dose Olanzapine Plus Granisetron and Dexamethasone for Carboplatin-Induced Nausea and Vomiting in Patients with Thoracic Malignancies: A Prospective Multicenter Phase II Trial.

BACKGROUND: Olanzapine is an inexpensive and durable agent for the treatment of chemotherapy-induced nausea and vomiting and is also superior to neurokinin-1 receptor antagonists in the control of nausea. This study aimed to investigate the efficacy and safety of a low dose of 5 mg olanzapine plus granisetron and dexamethasone for treatment of carboplatin (CBDCA)-induced nausea and vomiting in patients with thoracic malignancies. MATERIALS AND METHODS: We conducted a prospective, open-label, single-arm, multicenter, phase II trial in four centers in Japan. Registered patients were scheduled to receive area under the curve (AUC) ≥5 mg/mL per minute of CBDCA and had never received moderately to highly emetogenic chemotherapy. Patients received olanzapine 5 mg/day orally after supper for 4 days, in combination with granisetron and dexamethasone. Primary endpoint was complete response (CR; no emesis and no use of rescue medication) rate during the overall phase (0-120 hours). RESULTS: Between February 2018 and June 2020, 51 patients were enrolled, and 50 patients were evaluated. The CR rates in the overall (0-120 hours), acute (0-24 hours), and delayed phases (24-120 hours) were 94.0%, 100%, and 94.0%, respectively. No grade 3 or higher adverse effects of olanzapine were observed. CONCLUSION: Prophylactic antiemetic therapy with a low dose of 5 mg olanzapine plus granisetron and dexamethasone showed durable efficacy with an acceptable safety profile. This three-drug combination appears to be a reasonable treatment approach in patients with thoracic malignancies receiving an AUC ≥5 mg/mL per minute of CBDCA-based regimen. Clinical trial identification number: UMIN000031267. IMPLICATIONS FOR PRACTICE: The results of this phase II trial indicated that the prophylactic administration of low-dose of 5 mg olanzapine combined with granisetron and dexamethasone has promising activity with acceptable safety profile in patients with thoracic malignancy receiving high-dose carboplatin chemotherapy.

Primary Prophylaxis of Febrile Neutropenia With Pegfilgrastim in Small-cell Lung Cancer Patients Receiving Amrubicin as Second-line Therapy.

BACKGROUND/AIM: We evaluated the efficacy of primary prophylaxis with pegfilgrastim (PEG) for febrile neutropenia (FN) in small cell lung cancer (SCLC) patients receiving amrubicin (AMR). PATIENTS AND METHODS: A retrospective cohort study was conducted in patients with SCLC receiving AMR as second-line therapy. RESULTS: A total of 33 patients were treated with AMR (no PEG group), while 13 patients were treated with AMR plus prophylactic administration of PEG (PEG group). The severity of neutropenia was significantly reduced in the PEG group compared to the no PEG group (p=0.02). The incidence of FN in the no PEG and PEG groups was 27.3% and 7.7%, respectively. The time to development of FN tended to be longer in the PEG group compared to the no PEG group (p=0.132). CONCLUSION: Primary prophylaxis with PEG may be beneficial in reducing the risk of FN in patients with SCLC receiving AMR.

Immune thrombocytopenia induced by nivolumab in a patient with non-small cell lung cancer.

Antibodies targeting the receptor programmed death 1 on T cells have been approved for the treatment of lung cancer. Immune checkpoint inhibitors (ICIs) induce various immune-related adverse events. Life-threatening hematotoxicity can be provoked by ICI therapy. Although ICI-related endocrinopathy and interstitial lung disease have been well documented, hematotoxicity requiring intensive treatment is relatively rare. We describe a case of nivolumab induced thrombocytopenia after transient mild fever. A 77-year-old man with non-small cell lung cancer was administered nivolumab (240 mg/body, every 2 weeks) as second line therapy. On the day 2 after the first nivolumab infusion, he had a fever and his C-reactive protein level was elevated. Thoracic computed tomography revealed no interstitial lung disease or pneumonia. The fever resolved on day 9 and was not seen thereafter. On day 15 after the first nivolumab infusion, severe thrombocytopenia suddenly emerged. A bone marrow examination revealed no dysplasia or invasion. Based on the presence of high platelet-associated IgG titer, normal bone marrow plasticity and a lack of effectiveness of platelet infusion, we diagnosed nivolumab-induced immune thrombocytopenia. Daily administration of 60 mg of prednisolone restored the patient's platelet count and platelet-associated IgG. We also found that there was significant shrinkage of the primary lesion and that stable disease was achieved. One must be aware of this relatively rare side effect and the unusual clinical findings that could be associated with immunoreaction.