Background: Immune checkpoint inhibitors (ICIs) are the standard treatment for advanced lung cancer, but immune-related adverse events (irAEs) remain poorly understood, especially in a real-world setting.

Background Tyrosine kinase inhibitors (TKIs) can significantly prolong overall survival for patients with advanced non‐small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)‐mutation or anaplastic lymphoma kinase (ALK)‐rearrangement. However, the real‐world evaluation status of ALK/EGFR in China remains unclear. Methods We conducted a prospective study including 1134 patients with cytologically or histologically confirmed advanced NSCLC (stage IIIb–IV) at 12 Chinese hospitals. Results The most common evaluation methods were amplification‐refractory mutation system for EGFR status and immunohistochemistry targeting D5F3 for ALK status. Among patients with non‐squamous, the EGFR mutation rate was 44.1% and the ALK rearrangement rate was 10.0%. Among patients with squamous cell carcinoma, the EGFR mutation rate was 8.3% and the ALK rearrangement rate was 3.7%. Among all patients, gender (HR = 1.7, 95%CI = 1.2–2.4, P = 0.006), smoking history (HR = 1.8, 95%CI = 1.3–2.7, P = 0.001), histology (HR = 5.0, 95%CI = 2.4–10.1, P < 0.001), and brain metastases (HR = 1.5, 95%CI = 1.1–2.2, P = 0.017) were independent predictors of EGFR mutation, while age (HR = 2.6, 95%CI = 1.7–4.1, P < 0.001) was an independent predictor of ALK rearrangement. The median time from tumor diagnosis to EGFR or ALK status confirmation was 7 and 5 days, respectively. Targeted therapy rate was 73.8% in EGFR‐positive patients and 51.4% in ALK‐positive patients. There was a negative correlation between the first‐line targeted therapy rate and the EGFR mutation detection period (r = −0.152, P = 0.02), while no significant correlation among patients with ALK rearrangement (r = −0.179, P = 0.076). Conclusion Squamous NSCLC patients should also be routinely tested to determine their EGFR/ALK statuses. The first‐line targeted therapy rate remains low in Chinese patients with NSCLC.

Objective: to evaluate the risk of treatment-related adverse events of different severity and different system with PD-1 or PD-L1 inhibitors. Methods: randomized controlled trials (RCTs) that using PD-1/PD-L1 for cancer treatment were searched in the PubMed, Embase, Cochrane Library, and Web of Science from 1 January 2019 to 31 May 2021. Adverse events data were extracted from clinical trials website or original article by two authors separately. Meta-analysis was used to determine risk ratio (RR) and 95% confidence interval (95% CI) of adverse events in PD-1/PD-L1 inhibitors groups compared to that of control groups. Subgroup analyses were also performed. Results: a total of 5,807 studies were initially identified and after exclusion, 41 studies were included in meta-analysis. All the trials were international multicenter, randomized, phase II/III clinical trials, with the median follow-up of 27.5 months on average. Analysis of all grade adverse events showed that PD-1/PD-L1 inhibitors treatment significantly increased the risk of immune-related adverse events, including pruritus (RR: 2.34, 95% CI: 1.85–2.96), rash (RR: 1.53, 95% CI: 1.25–1.87), ALT elevation (RR 1.54, 95% CI 1.23–1.92), AST elevation (AST: RR 1.49, 95% CI 1.20–1.85), hepatitis (RR: 3.54, 95% CI: 1.96–6.38) and hypothyroid (RR: 5.29, 95% CI: 4.00–6.99) compared with that of control group. Besides that, PD-1/PD-L1 inhibitors were associated with higher risk of adverse events related to respiratory system including cough (RR: 1.33, 95% CI: 1.21–1.48), dyspnea (RR:1.23, 95% CI: 1.12–1.35) and chest pain (RR: 1.26, 95% CI: 1.07–1.47) compared with that of control groups in our meta-analysis and the dyspnea was taken high risk both in all grade and grade 3 or higher (RR: 1.55, 95% CI: 1.13–2.12). The risk of arthralgia was increased with PD-1/PD-L1 inhibitors (RR: 1.27, 95% CI: 1.10–1.47). Although the risk of myalgia was similar with PD-1/PD-L1 inhibitors and control groups, under subgroup analysis, PD-1/PD-L1 inhibitors decreased the risk of myalgia (RR: 0.56, 95% CI: 0.45–0.70) compared with that of chemotherapy. Conclusions: our results provide clear evidence that the risk of treatment-related adverse events in PD-1 or PD-L1 varies widely in different system. In particular, when using PD-1/PD-L1 inhibitors for oncology treatment, besides the common immune-related adverse events like pruritus, rash, hepatitis, and hypothyroid, the respiratory disorders and musculoskeletal disorders, such as cough, dyspnea, arthralgia, and myalgia, should also be taken into consideration.

Programmed cell death receptor-1 and its ligand-1 (PD-1/PD-L1) inhibitors have been applied to many cancers, but the difference of treatment-related adverse events (AEs) across cancer types remains unknown. We performed a meta-analysis and systemic review to compare the incidences of commonly reported all-grade AEs across cancer types and found that the most frequent AEs were fatigue, rash/pruritus, loss of appetite/nausea and diarrhea. However, each cancer type also had its higher incidences of AEs involving a relevant system, such as melanoma with epidermal AEs (rash, diarrhea and enterocolitis), lung cancer with dyspnea and pneumonitis, digestive system cancers with amylase and lipase elevation; and renal cell and urothelial cancer with kidney injury (creatinine elevation and proteinuria). However, the incidence of hepatitis did not follow the pattern to show a difference. We did another comparison between PD-1 and PD-L1 inhibitors in lung cancer and urothelial cancer respectively, and found that the risk of most AEs did not differ much, except for more hypothyroidism in PD-1 inhibitors, and more kidney injury in PD-L1 inhibitors. Besides possible immunological mechanisms for treatment-related AEs, the influence of previous radiotherapy and the clinical characteristics of the diseases themselves should also be considered and is worth further investigation. With the result of this meta-analysis, clinicians could estimate the risk of certain AE in certain cancer type, to make treatment options and to customize monitor strategies.

Epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (non-SCLC) benefits from first-line treatment with first generation tyrosine kinase inhibitors (TKIs). However, drug resistance is inevitable through different mechanisms and is dominated by the acquisition of the T790M mutation within EGFR, which occurs in ~50% of cases. The present study reports the case of a patient originally diagnosed with stage IA lung adenocarcinoma, with a recurrent tumor lesion in each side of the lungs following the surgical removal of the primary tumor. Erlotinib treatment of the recurrent tumors eliminated the tumor on the right side of the lung and resulted in the histological transformation of the tumor on the left side to SCLC following 6 years of treatment. Genetic profiling of the SCLC lesions using targeted next-generation sequencing identified different genetic alterations from the primary tumor, characterized by the newly acquired copy number loss of tumor protein p53 and transcriptional coreceptor 1, and the copy number gain of SRY-box 2. Continuation of treatment with chemotherapy and erlotinib demonstrated moderate disease control for ~1 year prior to the outbreak of a new lung lesion. Liquid biopsy profiling of circulating tumor DNA revealed the acquisition of KRAS proto-oncogene, GTPase (KRAS) p.G12C mutation, indicating the occurrence of another resistance mechanism to erlotinib. During erlotinib treatment, the lung adenocarcinoma progressed through two atypical mechanisms, notably from the transformation to SCLC and the acquisition of the KRAS mutation to surpass EGFR inhibition. However, the combinational and interchanging usage of chemotherapy and TKI resulted in persistent and effective disease control.