bevacizumab (BP 01 / Bevqolva / BP01)

Early-onset duodenal perforation during bevacizumab-containing chemotherapy in a patient with ovarian cancer: a case report.

Nagase Satoshi S, Taguchi Keisuke K, Yoshida Takanori T, Matsumoto Shokei S et al.

Bevacizumab-induced gastrointestinal perforation is a potentially fatal adverse event. However, duodenal perforations are rare. Conversely, patients with cancer often have concomitant rheumatoid arthritis and may be treated with a combination of anti-rheumatic drugs and symptomatic medications; however, the effects of these concomitant medications on bevacizumab-related perforation remain understudied. This report describes the case of a patient with ovarian cancer and a history of anti-rheumatic drug treatment who developed early-onset duodenal perforation during bevacizumab-containing chemotherapy, highlighting the importance of assessing the risk of duodenal perforation and the provision of multidisciplinary management. The patient was a woman in her 50s with ovarian cancer that metastasized to the para-aortic lymph nodes. She was diagnosed with platinum-sensitive recurrence, and combination therapy with gemcitabine, carboplatin, and bevacizumab was initiated. She was also taking iguratimod and methotrexate for rheumatoid arthritis treatment. The patient developed sudden abdominal pain during the second course of chemotherapy and presented to the emergency department. A computed tomography (CT) scan revealed free gas, raising the suspicion of gastrointestinal perforation. Emergency laparotomy confirmed a duodenal perforation that was surgically covered with the ligamentum teres hepatis. A perforation of <1 cm was found in the anterior wall of the duodenal bulb, but the postoperative course was uneventful. The patient was discharged on postoperative day 7 and continued chemotherapy without bevacizumab. Postoperative upper endoscopy revealed an H2 stage ulcer. When administering bevacizumab to patients with ovarian cancer and multiple perforation risk factors, careful consideration should be given to evaluating existing ulcers, appropriately using concomitant medications, and modifying perforation risk factors to avoid serious adverse events. Therefore, collaboration between a multidisciplinary team, including oncologists, rheumatologists, and pharmacists, is crucial for appropriate drug use and continuous monitoring.

Brain-shuttle biologics chart new paths across the blood-brain barrier.

Dolgin Elie E

Integrated Evaluation of Survival, Surgical Conversion, and Toxicity for Induction Therapy in Initially Unresectable Colorectal Liver Metastases: An Individual Patient Data Network Meta-analysis.

Nie Guilin G, Li Xinming X, Wang Yaoqun Y, Xu Jianrong J et al.

Patients with initially unresectable colorectal cancer liver metastases (CRLM) could derive benefits from active induction regimens by increasing the likelihood of surgical conversion. However, the comparative benefit-risk profiles of currently available regimens remain unclear. We performed an individual patient data (IPD) and network meta-analysis (NMA) to compare the efficacy of active induction regimens. IPD was reconstructed from randomized controlled trials (RCTs). The primary outcome was progression-free survival (PFS). Secondary outcomes included R0-1 resection rate, overall survival (OS), and grade ≥ 3 adverse events (AEs). Subgroup analyses were conducted according to KRAS/BRAF status and primary tumor sidedness. An entropy-weighted TOPSIS model was used to integrate efficacy and safety outcomes. Seven RCTs involving 1368 patients were included. IPD-based network analysis suggested that bevacizumab + triplet-chemotherapy was associated with the highest probability of improving R0-1 resection rate (0.99) and prolonging PFS (0.99). No significant differences in OS were observed among targeted therapy-based regimens. For patients with KRAS/BRAF wild-type tumors, cetuximab + doublet-chemotherapy is the only therapy performed better than chemotherapy in prolonging PFS. Bevacizumab + triplet-chemotherapy demonstrated superior efficacy among patients with KRAS/BRAF-mutant tumors. No significant PFS differences were observed among therapies in both left-sided and right-sided. Bevacizumab + doublet-chemotherapy demonstrated a more balanced benefit-risk profile with the highest Topsis scores (0.67). Bevacizumab plus triplet chemotherapy improves disease control and surgical conversion benefits but is associated with greater toxicity. Bevacizumab plus doublet chemotherapy showed the most favorable benefit-risk balance and may represent an optimal compromise for patients with initially unresectable CRLM.

A 24-Year-Old Man with Disseminated Tuberculosis and A Corticosteroid-Refractory Paradoxical Reaction to Anti-Tuberculous Treatment.

Charalampidis Charalampos C, Karantana Valentina V, Kavatha Dimitra D, Tsiodras Sotirios S et al.

Paradoxical reactions during anti-tuberculosis treatment are immune-mediated reactions that complicate treatment even in immunocompetent patients. We present the case of a previously healthy 24-year-old man with disseminated tuberculosis, who experienced persistent fever, weight loss, and radiological deterioration despite appropriate treatment. These findings were consistent with a paradoxical reaction to treatment, after extensive work-up excluded treatment failure, co-infections, and systemic inflammatory conditions. However, high-dose corticosteroids failed to achieve improvement. Ultimately, an interleukin-1 receptor antagonist (anakinra) was initiated as a salvage therapy for this corticosteroid-refractory paradoxical reaction, resulting in rapid defervescence, normalization of inflammatory markers, and radiological improvement. This case underscores the diagnostic and therapeutic challenges when managing severe reactions in tuberculosis patients, while highlighting the importance of biologics like anakinra in corticosteroid-refractory paradoxical reactions. Paradoxical reactions to anti-tuberculosis treatment remain an overlooked cause of non-resolving fever in immunocompetent and immunocompromised patients with tuberculosis and should be considered after ruling out treatment-refractory or complicated infection in persistently febrile patients.Prompt treatment of severe reactions prevents major complications and improves clinical outcomes.Corticosteroid-refractory paradoxical reactions illustrate the potential role of biologics, such as tumour necrosis factor inhibitors and, in our case, interleukin-1 receptor antagonists, in controlling excessive inflammation in tuberculosis.