Introduction. Objective response rates (ORR) appear to be higher in melanoma patients who develop immune-related adverse events (irAEs), but whether there is a similar association between irAEs and survival remains unknown. Materials and Methods. Patients with advanced melanoma treated with single-agent pembrolizumab or nivolumab in the province of Alberta from June 2014 to May 2017 were identified through the provincial pharmacy database. Chart review identified and categorized all irAEs that occurred while on anti-programmed cell death protein 1 (PD-1) checkpoint inhibitors. The primary objective was to compare overall survival (OS) with patients who developed any irAEs versus those who did not. Secondary outcomes included progression-free survival (PFS) and ORR. Results. Among 186 patients, any-grade and grade ≥3 irAEs occurred in 88 (47%) and 27 (15%) patients, respectively; one patient died of pneumonitis. In a landmark analysis excluding patients who died within the first 12 weeks, the median follow-up was 24 months, 20 months in patients without any irAEs and 26 months in patients with irAEs (p = .006). Median OS was 39 versus 23 months (hazard ratio [HR], 0.46; p = .001) for any irAE and no irAE, respectively, and median OS not reached versus 29 months for grade ≥3 irAEs and no grade ≥3 irAEs, respectively. In multivariate analysis, elevated lactate dehydrogenase correlated with reduced OS (HR, 2.34; p = .001), whereas each additional cycle of treatment received (HR, 0.94; p < .001) and development of grade ≥3 irAEs (HR, 0.29, p = .024) were significantly associated with longer OS. Conclusion. Anti-PD-1-associated grade ≥3 irAEs in patients with advanced melanoma is associated with better patient outcomes, including overall survival. The Oncologist 2020;25:438-446 Implications for Practice: Previous prospective randomized clinical trials demonstrate improved response rates in patients with melanoma who develop select adverse events. The current population-based real-world study in advanced melanoma reports an association with anti-programmed cell death protein 1 (PD-1)-induced grade ≥3 immune-related adverse events (irAEs) and better patient outcomes, including overall survival. These results suggest that irAEs may be a manifestation of a patient's ability to mount a systemic immune response from PD-1-directed therapies, which may be associated with therapeutic benefit. The finding of irAEs coinciding with clinical benefit from these therapies supposes that these events are, by and large, unavoidable, and the critical management of irAEs remains essential for optimizing patient outcomes.

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Background Recurrence is not explicitly documented in cancer registry data that are widely used for research. Patterns of events after initial treatment such as oncology visits, re-operation, and receipt of subsequent chemotherapy or radiation may indicate recurrence. This study aimed to develop and validate algorithms for identifying breast cancer recurrence using routinely collected administrative data. Methods The study cohort included all young (≤ 40 years) breast cancer patients (2007–2010), and all patients receiving neoadjuvant chemotherapy (2012–2014) in Alberta, Canada. Health events (including mastectomy, chemotherapy, radiation, biopsy and specialist visits) were obtained from provincial administrative data. The algorithms were developed using classification and regression tree (CART) models and validated against primary chart review. Results Among 598 patients, 121 (20.2%) had recurrence after a median follow-up of 4 years. The high sensitivity algorithm achieved 94.2% (95% CI: 90.1–98.4%) sensitivity, 93.7% (91.5–95.9%) specificity, 79.2% (72.5–85.8%) positive predictive value (PPV), and 98.5% (97.3–99.6%) negative predictive value (NPV). The high PPV algorithm had 75.2% (67.5–82.9%) sensitivity, 98.3% (97.2–99.5%) specificity, 91.9% (86.6–97.3%) PPV, and 94% (91.9–96.1%) NPV. Combining high PPV and high sensitivity algorithms with additional (7.5%) chart review to resolve discordant cases resulted in 94.2% (90.1–98.4%) sensitivity, 98.3% (97.2–99.5%) specificity, 93.4% (89.1–97.8%) PPV, and 98.5% (97.4–99.6%) NPV. Conclusion The proposed algorithms based on routinely collected administrative data achieved favorably high validity for identifying breast cancer recurrences in a universal healthcare system in Canada. Electronic supplementary material The online version of this article (10.1186/s12885-019-5432-8) contains supplementary material, which is available to authorized users.

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