Background: Immune checkpoint inhibitor-induced pancreatic injury (ICI-PI) is a rare immunotoxicity, with limited data on treatment and long-term outcomes. Methods: PubMed, EMBASE, and Cochrane Library were systematically searched for studies reporting ICI-PI in patients with solid malignancies. ICI-PI was defined as pancreatic inflammation post-ICI exposure, diagnosed via radiologic changes or elevated lipase/amylase levels without other underlying causes. The CTCAE grading system was used. The primary objectives were to assess the frequency, severity, serum abnormalities, management, and long-term outcomes. We conducted a proportional single-arm meta-analysis with a random effects model. Results: The analysis included 25 retrospective studies involving 48,704 patients. Tumor types included thoracic/head and neck (38%), skin (26%), genitourinary/gynecological (18%), gastrointestinal (12%), and others (6%). The median age ranged from 56 to 73 years, with a follow-up from 2.5 to 45.9 months. ICI-PI occurred in 3.60% (95% CI: 1.64–6.28%) of patients, with grade ≥ 3 toxicity in 59.45% (95% CI: 35.32–81.37%). The frequency rates of ICI-PI were 1.99% for CTLA4 inhibitors, 5.01% for PD(L)1 inhibitors, and 7.44% for combination ICI therapy (p < 0.01). The median time to onset from treatment initiation ranged from 30 to 390 days, and symptom resolution ranged from 55 to 84 days. Management included corticosteroids (30.20%), intravenous fluids (22.82%), and hospitalization (30.46%). Chronic complications affected 63.54% (95% CI: 29.03–91.56%), including primarily diabetes mellitus (DM 89.45%; 95% CI: 61.88–100.0%) and exocrine pancreatic insufficiency (EPI 10.55%; 95%: 0.0–38.12%). ICI-PI recurrence occurred in 27.2% of those resuming ICI therapy. The objective response rate was 61.7% (95% CI: 55.08–68.17%). Conclusions: ICI-PI, though infrequent, is severe and predisposes patients to chronic complications, including DM and EPI.

The RET proto-oncogene, which encodes a receptor tyrosine kinase, is an important factor in the pathogenesis of medullary and papillary thyroid cancers. Selpercatinib and pralsetinib, both specific RET-kinase inhibitors, are the only FDA-approved drugs for treating RET-altered thyroid cancer. We wanted to evaluate the safety and efficacy of selpercatinib and pralsetinib in RET-altered thyroid cancers. We searched the PubMed, Embase, Cochrane, and Clinicaltrials.gov databases for randomized controlled trials and observational studies published up to March 30, 2024, and included those that reported any of the desired endpoints. The primary endpoints were 1-year progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Quantitative analyses were performed using the R programming language. We included four studies with 560 patients, 510 with RET-mutant and 50 with RET-fusion thyroid cancer. The 1-year PFS was 84% (95% CI, 79–88, I2 = 43%), ORR was 69% (95% CI, 65–73, I2 = 0) and DCR was 93% (95% CI, 89–96, I2 = 44%). Some important grade ≥3 adverse events were hypertension (16%; 95% CI, 11–22; I2 = 43%), diarrhea (3%; 95% CI, 2–5; I2 = 0), increased ALT (11%; 95% CI, 8–14; I2 = 0) and increased AST (6%; 95% CI, 4–10; I2 = 0). In conclusion, these findings suggest that selpercatinib and pralsetinib are efficacious and safe for use in patients with RET-altered thyroid cancer.

Piya IJ, et al. J Gynecol Oncol. 2025 Oct;37:e29. https://doi.org/10.3802/jgo.2026.37.e29