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We retrospectively analyzed non–small cell lung cancer (NSCLC) patients from a single center treated with pembrolizumab on the KEYNOTE-001 trial and evaluated the association between treatment-related adverse events (trAEs) and clinical outcomes. Investigators reported AEs on trial and graded them according to Common Terminology Criteria for Adverse Events v4.0, labeling them as unlikely, possibly, or probably treatment-related. AEs labeled as possibly/probably related were considered trAEs for this analysis. The relationship between the incidence of a trAE and clinical outcomes was evaluated. Ninety-seven NSCLC patients treated on KEYNOTE-001 at the University of California, Los Angeles were evaluated. Ten percent (85/826) of AEs were trAEs, occurring in 40% (39/97) of patients. The most frequent trAEs were rash (21% patients), fatigue (6% patients), and hypothyroidism (6% patients). The 39 patients that experienced a trAE had increased objective response rate (ORR, 38.5%), progression-free survival (PFS: median, 248 days), and overall survival (OS: median, 493 days), compared with the 58 patients that did not (ORR: 8.9%, PFS: median 60 days, OS: median 144.5 days). The observed association between trAEs and improved clinical outcome persisted when using Cox proportional hazards regression models to assess the confounding effect of covariates and mitigate guarantee-time bias. The association also remained when data were substratified by grade, degree of association, and treatment-related select AE designation. This single-center analysis revealed that trAEs predicted for improved clinical outcome with pembrolizumab, and when controlling for guarantee-time bias and plausible confounders, this association remained. This observed relationship adds to our understanding of anti–PD-1 therapy and could aid clinicians in identifying patients most likely to benefit from therapy. Cancer Immunol Res; 6(3); 288–94. ©2018 AACR.

Table S2: Demographics of the 97 NSCLC patients treated at UCLA on KEYNOTE-001 (N=97) compared with the demographics of the total KEYNOTE-001 study population (n=495). Of note, the UCLA cohort of 97 patients is included in the total KEYNOTE-001 study population of 495 patients.

Table S3: The occurrence of a treatment related AE (trAE) in the 97 patients treated at UCLA on the KEYNOTE-001 clinical trial, stratified by a history of thoracic radiation therapy (TRT) or prior radiation therapy to any location. P values computed via Fisher's exact test.

Supplementary Table S6a: Objective response rate (ORR) in the 95 NSCLC patients from the UCLA cohort that had at least 1 set of thyroid values obtained on trial available for analysis stratified by the presence or absence of an abnormal TSH value of varying qualities (Any, High, Low, Both High and Low noted).

Supplementary Table S5a: Cox proportional hazards models for progression-free survival (PFS) with number of treatment related select adverse events included as a time-varying covariate. Listed are results from both unadjusted models and adjusted models. Hazard ratio estimates marked '(+1)' correspond to the incremental effect of a unit increase in the relevant predictor.

Table S1: All adverse events occurring in > 5% of patients in the UCLA NSCLC cohort of 97 patients treated on KEYNOTE-001.

Supplementary Table 4a: Objective response rate (ORR), progression-free survival (PFS), and overall survival stratified by the incidence of a grade 2 or higher treatment related AE (trAE) or a trAE of varying degrees of attribution (possible or probable). Included are all 97 NSCLC patients treated at UCLA on KEYNOTE-001 with available follow-up data.

Supplementary Figure S1A-B. ORR, PFS, and OS analysis for UCLA NSCLC cohort of KEYNOTE-001 trial. ORR, PFS, and OS for all 97 patients in the UCLA cohort of the KEYNOTE-001 trial stratified by the occurrence of a (A) treatment related adverse event (trAE) or (B) a treatment related select AE.

Purpose/objectives To discuss the response patterns and side effects related to ipilimumab, a new immunotherapeutic agent under investigation in the treatment of advanced melanoma and other malignancies. Data sources Published articles, abstracts, research data, and clinical experience. Data synthesis Ipilimumab is a fully human monoclonal antibody that inhibits the activity of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a naturally immunosuppressive molecule. The most common side effects are immune mediated (e.g., inflammatory diarrhea, pruritus) and appear to occur as a direct result of CTLA-4 inhibition and enhanced immune system activation. Side effects generally are grade I or II and resolve with standard treatments. Most grade III or IV events are managed successfully after swift diagnosis and treatment with corticosteroids; steroid-refractory events resolve after treatment with infliximab or mycophenolate. Conclusions The response patterns and side effects associated with ipilimumab therapy greatly differ from those common to other advanced melanoma therapies (e.g., chemotherapy, cytokines, vaccines). Implications for nursing Nurses have an important role in educating patients about the differences between anti-CTLA-4 therapy and chemotherapy. In addition, teaching patients to recognize ipilimumab's side effects and report them early can result in fast treatment to prevent symptom progression from grade I or II to III or IV. Communication between nurses and patients throughout the treatment process will help patients benefit maximally from the new therapeutic strategy.

Patients with advanced melanoma have few treatment options, and survival is poor. However, improved understanding of how the immune system interacts with cancer has led to the development of novel therapies. Ipilimumab is a monoclonal antibody that inhibits cytotoxic T-lymphocyte antigen-4 (CTLA-4), a key negative regulator of host T-cell responses. This article presents cases of patients receiving ipilimumab in clinical trials along with a discussion of their significance and relevance to nursing practice. The patients showed different response patterns to ipilimumab and also had various typical immune-related adverse events (irAEs), which were managed successfully. The atypical response patterns produced by ipilimumab likely reflect its mechanism of action, which requires time for the immune system to mount an effective antitumor response. Meanwhile, lesions may appear to enlarge as a consequence of enhanced T-cell infiltration, although this may not necessarily be true disease progression. Patients receiving ipilimumab may respond very differently compared to how they might react to chemotherapy. Responses can take weeks or months to develop; therefore, clinicians should not terminate treatment prematurely, providing the patient's condition allows for continuation. Early recognition of irAEs combined with prompt management will ensure that events are more likely to resolve without serious consequences.