Immune checkpoint inhibitor therapy (icit) is now a standard of care for a variety of cancers in both the metastatic and adjuvant settings. As a result, an understanding of the timing, epidemiology, monitoring, diagnosis, and management of immune-related adverse events (iraes) associated with icit is imperative. This article reviews specific iraes by organ system, consolidating recommendations from multiple guidelines and incorporating data from case reports to highlight additional evolving therapeutic options for patients. Managing iraes requires early recognition, early intervention, and education of the patients and the multidisciplinary health care team alike. Given the durable responses observed with icit, and the irreversible nature of some of the iraes, further research into management of the sequelae of icit is required.

Immune checkpoint and MAP kinase pathway inhibitors can significantly improve long-term survival for patients with melanoma. There is limited real-world data of these regimens’ effectiveness. We retrospectively analyzed 402 patients with unresectable and metastatic melanoma between August 2013 and July 2020 treated with immune checkpoint inhibitors and MAP kinase pathway targeted therapy in Alberta, Canada. Overall survival (OS) was compared using Kaplan–Meier and Cox regression analyses. Subgroup survival outcomes were analyzed by first-line treatment regime and BRAF mutation status. Three treatment eras were defined based on drug access: prior to August 2013, August 2013 to November 2016, and November 2016 to July 2020. Across each era, there were improvements in median OS: 11.7 months, 15.9 months, and 33.6 months, respectively. Patients with BRAF mutant melanoma had improved median OS when they were treated with immunotherapy in the first line as opposed to targeted therapy (median OS not reached for immunotherapy versus 17.4 months with targeted treatment). Patients with BRAF wild-type melanomas had improved survival with ipilimumab and nivolumab versus those treated with a single-agent PD-1 inhibitor (median OS not reached and 21.2 months). Our real-world analysis confirms significant survival improvements with each subsequent introduction of novel therapies for advanced melanoma.

Immune checkpoint inhibitor (ICI)-induced insulin-dependent diabetes mellitus (IDDM) is a rare but potentially fatal immune-related adverse event (irAE). In this multicentre retrospective cohort study, we describe the characteristics of ICI-induced IDDM in patients treated across five Canadian cancer centres, as well as their tumor response rates and survival. In 34 patients identified, 25 (74%) were male and 19 (56%) had melanoma. All patients received anti-programed death 1 (anti-PD1) or anti-programmed death ligand-1 (anti-PD-L1)-based therapy. From ICI initiation, median time to onset of IDDM was 2.4 months (95% CI 1.1–3.6). Patients treated with anti-PD1/PD-L1 in combination with an anti-cytotoxic T lymphocyte antigen 4 antibody developed IDDM earlier compared with patients on monotherapy (1.4 vs. 3.9 months, p = 0.05). Diabetic ketoacidosis occurred in 21 (62%) patients. Amongst 30 patients evaluable for response, 10 (33%) had a complete response and another 10 (33%) had a partial response. Median overall survival was not reached (95% CI NE; median follow-up 31.7 months). All patients remained insulin-dependent at the end of follow-up. We observed that ICI-induced IDDM is an irreversible irAE and may be associated with a high response rate and prolonged survival.

3532 Background: The VPN [JCO 2011;29(23)] is a tool used for individualized prognostication in rectal cancer, and the recently described NAR score [Yothers et al. JCO 32, 2014 abst: 38] has been suggested as a surrogate endpoint for overall survival (OS) in clinical trials. However, these tools have not been validated outside of the clinical trial setting. We assessed these models in a retrospective multi-institution database, to determine their predictive ability for outcome in patients with rectal cancer treated with neoadjuvant chemoradiation (nCRT). Methods: Data from patients with locally advanced rectal cancer who received nCRT and had curative intent surgery from 2005 to 2012 were collected from Tom Baker Cancer Center, Cross Cancer Institute, BC Cancer Agency, Ottawa Hospital Cancer Centre and Dr. H. Bliss Murphy Cancer Centre. The NAR score was compared with pathologic complete response (pCR) status for OS and with the VPN for local control (LC), distant control (DC) and OS using Akaike’s information criterion (AIC – a tool for comparing models in a dataset). C-index was evaluated for VPN and NAR for OS. Results: 1,172 patients were included; pCR was achieved in 16.6%.The median NAR score was 17.36; NAR risk groups included low (22.6%), intermediate (42.6%), and high (34.9%). The 5-year OS in the NAR risk groups were 88.1% (low), 82% (intermediate – HR 1.89, 95% CI 1.13 – 3.1), 59.5% (high – HR 5.05, 95% CI 3.1 – 8.2), and 89.9% for pCR (HR 0.25, 95% CI 0.14 – 0.45) versus 73.1 % for no pCR (log rank p-value <0.0001 for both). AIC favoured NAR compared with pCR for OS (2,549.6 v 2,824.0).VPN as a continuous variable predicted LC (HR 0.97, 95% CI 0.95-0.99, p=0.015), DC (HR 0.98, 95% CI 0.98-0.99, p<0.0001) and OS (HR 0.96, 95% CI 0.95-0.96, p<0.0001). The AIC favoured VPN over NAR for LC (851.2 v 856.5), DC (2,154.5 v 2,160.6) and OS (2,455.3 v 2,549.6). C-index also favoured VPN over NAR for OS (0.697 v 0.66). Conclusions: Similar to recent clinical trial data, NAR outperformed pCR in predicting OS, and the VPN was significantly associated with LC, DC and OS in the non-clinical trial setting. VPN appeared to better predict LC, DC, and OS compared with the NAR score and is favoured for individual patient prognostication.

Complementary medicines (CM) are frequently used by patients with cancer. Controversy exists over the effectiveness and risk that CM may add to conventional cancer therapy. The incidence of CM use among patients enrolled in phase III clinical trials is unknown. Medication lists from 6 international phase III clinical trials were retrospectively reviewed to identify patients using CM. Patients had metastatic breast, colorectal, or lung cancers. Quality of life, adverse events, overall survival, and progression-free survival were compared between CM users and non-users. Baseline differences between groups were adjusted with propensity score matching groups. Seven hundred and six of 3446 patients (20.5%) used at least one CM. CM use was highest among patients with breast cancer (35.6%). CM users had more favorable baseline prognostic factors (ECOG 0-1, non-smoking status, younger age, and fewer metastases). CM use was associated with lower rates of adverse events (50% vs. 62%, P = .002) and quality of life was similar between both groups. After adjustment with propensity score matching, CM use was also associated with longer overall survival in patients with lung cancer (adjusted hazard ratio 0.80, 95%CI, 0.68-0.94, P =.0054). However, several key control variables like EGFR status were not available. One in 5 patients in phase III clinical trials report using CM. CM was not associated with worse cancer-specific outcomes. However, CM users had more favorable baseline prognostic factors, and likely other confounders that may have contributed to improved outcomes observed in the lung cohort. Physicians should monitor for CM use and potential interactions with clinical trial drugs.