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Programmed cell-death 1 antibodies (PD-1 Ab) improve overall survival (OS) for patients with advanced melanoma in trials; however, safety data in patients ≥75 years are lacking. The prognostic significance of and risk factors for PD-1 Ab discontinuation due immune related adverse events (irAE) are also uncertain.Patients with advanced melanoma receiving frontline PD-1 Ab at British Columbia Cancer outside of clinical trials between 10/2015-10/2019 were retrospectively analyzed. The incidence and subtypes of irAE were compared between age subgroups75 and ≥ 75 years. Univariable logistic regression identified variables associated with treatment discontinuation within four months of PD-1 Ab initiation. Cox proportional hazard regression models were used to determine factors significantly associated with OS.302 patients were identified, of whom 126 (41.7%) were ≥ 75 years. During all follow-up, 15.9% of patients experienced irAE grade 3/4 and 27.2% of the cohort stopped PD-1 Ab due to immune toxicity. irAE incidence, hospitalization, and need for steroids by the four-month landmark were similar amongst age groups. Advanced age was not associated with risk of PD-1 Ab discontinuation from irAE on logistic regression. For the entire cohort, pre-treatment factors associated with shorter OS on multivariable analysis were ECOG performance status ≥1, M1d stage, lactate dehydrogenase224, and neutrophil/ lymphocyte ratio ≥ 5. On four-month landmark multivariable analysis, treatment discontinuation due to irAE was significantly associated with worse OS.Patients aged ≥75 years experienced similar irAE rates and treatment discontinuation for immune toxicity compared to younger patients. As PD-1 Ab discontinuation due to irAE was associated with shorter OS, efforts to treat irAE early are warranted to potentially avoid therapy cessation.

Aims Induction ipilimumab and nivolumab followed by maintenance nivolumab improve overall survival compared with ipilimumab alone in patients with advanced melanoma, but immune-related adverse events (irAE) occur commonly. The need for induction discontinuation because of irAE and the relationship between irAE and survival in non-trials patients are unclear. Materials and methods Patients with unresectable stage III–IV melanoma receiving first-line combination immunotherapy at one of six centres between December 2017 and February 2020 outside of trials were identified retrospectively. Landmark 12-week Kaplan–Meier analyses and log-rank tests were used to evaluate associations between discontinuation of induction therapy on overall survival and time to treatment failure (TTF). Multivariable analysis of factors influencing overall survival and TTF was undertaken. Results Among 95 patients, the median age was 62 years, 38.9% had Eastern Cooperative Oncology Group performance status ≥1 and 22.1% had brain metastases. The median follow-up for the whole cohort was 19.8 months by the reverse Kaplan–Meier method. Any grade and grade 3–4 irAE were noted in 78.9% and 44.2% of the cohort, respectively. 44.2% of patients completed induction immunotherapy, whereas 41.1% did not due to irAE. Twelve-week landmark overall survival and TTF were similar in patients who completed induction versus those who did not due to irAE. On multivariable analysis, any grade irAE (versus none) was associated with longer overall survival (hazard ratio = 0.35, 95% confidence interval 0.15–0.82, P = 0.02) and TTF (hazard ratio = 0.38, 95% confidence interval = 0.17–0.81, P = 0.01). Grade 3–4 irAE correlated with longer TTF (hazard ratio = 0.45, 95% confidence interval = 0.20–1.01, P = 0.05). Conclusion In this population-based cohort, discontinuation of induction immunotherapy as a result of irAE did not adversely affect overall survival or TTF. irAE observed during ipilimumab and nivolumab induction were associated with improved survival outcomes.

The COVID-19 pandemic changed diagnostic and treatment pathways in oncology. We compared the safety and efficacy of pembrolizumab amongst advanced nonsmall cell lung cancer (NSCLC) patients with a PD-L1 tumor proportion score (TPS) ≥ 50% before and during the pandemic.Advanced NSCLC patients initiating pembrolizumab between June 2015 and December 2019 ("pre-pandemic cohort") and between March 2020 and March 2021 ("pandemic cohort") at BC Cancer were identified retrospectively. Multivariable logistic regression evaluated risk factors for immune-related adverse events (irAE) ≥ grade 3 at the 6 week, 3 month, and 6 month landmarks. Cox regression models of overall survival (OS) were constructed.The study population comprised 417 patients in the pre-pandemic cohort and 111 patients in the pandemic cohort. Between March and May 2020, 48% fewer advanced NSCLC cases with PD-L1 TPS ≥ 50% were diagnosed compared to similar intervals in 2018-2019. Telemedicine assessment [new patient consultations (p 0.001) and follow-up (p 0.001)] and extended interval pembrolizumab dosing (p 0.001) were more common in the pandemic cohort. Patients initiating pembrolizumab after February 2020 (vs. before January 2020) experienced similar odds of developing severe irAE. 2/111 (1.8%) patients receiving pembrolizumab during the pandemic tested positive for COVID-19. On multivariable analysis, no association between pembrolizumab treatment period (before vs. during the COVID-19 pandemic) and OS was observed (p = 0.18).Significant changes in healthcare delivery in response to the pandemic did not result in increased high grade toxicity or lower survival outcomes in patients with advanced NSCLC treated with pembrolizumab.

BACKGROUND: We investigated the association of peripheral blood inflammatory markers with overall survival (OS) in pembrolizumab treated advanced non-small cell lung cancer (aNSCLC) patients with programmed death ligand 1 (PD-L1) expression ≥50%. Clinical risk factors for development of immune-related adverse events (irAE) were also explored. METHODS: aNSCLC patients with high PD-L1 expression receiving pembrolizumab monotherapy outside of clinical trials were identified retrospectively. All patients were treated at one of six British Columbia Cancer clinics between August 2017 and June 2019. Patients were dichotomized using baseline neutrophil-to-lymphocyte ratio (NLR

Background The anti-programmed cell death one antibodies (Anti-PD-1 Ab) pembrolizumab or nivolumab are commonly prescribed to patients with advanced melanoma. The purpose of the current study is to identify baseline clinical characteristics associated with time to treatment initiation (TTI) of pembrolizumab or nivolumab for advanced melanoma and whether treatment delays are associated with differences in survival outcomes. Methods All patients receiving Anti-PD-1 Ab as a first-line treatment for advanced melanoma outside of clinical trials at British Columbia Cancer Agency between 10/2015 and 10/2019 were identified retrospectively. TTI was defined as the interval from pathologic diagnosis of advanced melanoma to first Anti-PD-1 Ab treatment. To determine the association between TTI and baseline characteristics, multivariable Cox proportional hazard regression analyses provided an estimate of the instantaneous relative risk of starting treatment at any time point (hazard ratio [HR] >1 indicates shorter TTI). To describe changes in overall survival (OS) observed for each four-week delay in treatment initiation, multivariable cox proportional hazard regression modelling was also performed. Results In a cohort of 302 patients, the median TTI was 52 days (interquartile range 30.2-99.0). Pulmonary metastases (M1b)/non-central nervous system visceral metastases (M1c) vs. metastases to skin or non-regional lymph nodes (M1a)(HR=1.50, 95% CI=1.12-2.02; p=0.007) and pre-treatment Eastern Cooperative Oncology Group Performance Status (ECOG PS) >1 (vs 0/1, HR=1.50, 95% CI= 1.11-2.01; p=0.008) were associated with earlier TTI. An association between treatment delay and improved OS was observed. Conclusion Patients having visceral metastases and poor baseline ECOG PS were more likely to initiate Anti-PD-1 Ab sooner. The association of shorter TTI with worse OS likely represents confounding by indication (urgent treatment offered to patients with aggressive disease).

While pembrolizumab improves overall survival (OS) in a subset of advanced nonsmall cell lung cancer (aNSCLC) patients (pts) in clinical trials, individuals with poor Eastern Cooperative Oncology Group performance status (ECOG PS) were excluded. Furthermore, some studies have identified a potential link between improved pt outcomes and development of immune related adverse events (irAE.) In a large provincial cohort, we studied the efficacy and safety of pembrolizumab for poor ECOG PS pts and whether irAE correlate with improved OS.aNSCLC pts treated with pembrolizumab between 06/2015 and 08/2018 at BC Cancer were retrospectively identified. Kaplan-Meier curves of OS from initiation of pembrolizumab were plotted. 3-, 6-, and 9- month landmark Kaplan-Meier analysis was performed and log-rank tests used to determine an association of irAE subtypes with OS. Multivariable logistic regression identified variables associated with grade ≥3 irAE within 3 months of pembrolizumab initiation.Of 190 pts, 74.2% were treatment naïve and 92.6% had PD-L1 expression ≥ 50%. Median OS in the 1st line and ≥2nd line settings were 24.3 months (95% CI, 9.7-not reached, NR) and 13.4 months (95% CI, 8.1-NR), respectively. Pts with ECOG PS 2/3 had lower median OS than if ECOG PS 0/1 (5.8 months vs. 16.7 months, p 0.0001). In multivariable analysis, the odds of grade ≥ 3 irAE within 3 months was 6.3 fold higher if ECOG PS 2/3 versus 0/1 (p = 0.05). Development of pneumonitis at the 9 month landmark weakly correlated with decreased OS (p = 0.09).In the studied cohort, ECOG PS 2/3 pts had a significantly lower OS and greater odds of experiencing high-grade irAE than if ECOG PS 0/1. Development of irAE did not result in improved OS. Randomized trials to determine benefit of pembrolizumab for poor ECOG PS pts are needed.

Objectives To explore the association of age with development of immune related adverse events (irAE) and survival in patients with advanced nonsmall cell lung cancer (aNSCLC) receiving programmed cell death 1 antibodies (PD-1 Ab) outside of clinical trials. Methods A multicenter retrospective study of PD-1 Ab prescription for patients with aNSCLC between 06/2015–11/2018 at BC Cancer. Multivariable (MVA) logistic regression identified baseline variables associated with irAE manifested within 3 months of PD-1 Ab initiation. Overall survival (OS) analyzed in a propensity-score matched cohort and survival outcomes compared between age groups by stratified log-rank. Six-week landmark analysis was performed and OS compared between patients with interrupted versus continuous treatment by log-rank. Results Of 527 patients, 40.6% were age ≤ 64 years, 40.6% were 65–74 years, and 18.8% were ≥ 75 years. In MVA, ECOG performance status 2/3 (p = .034), squamous histology (p = .031), and nivolumab therapy (vs. pembrolizumab, p = .012) were associated with increased odds of irAE by 3 months of treatment. Across age groups no difference existed in any grade irAE (p = .98), hospitalization (p = 1.0), or corticosteroids use (p = .51). The propensity score–matched survival analysis comprised 77 patients from each age group; all covariates were balanced. OS did not differ significantly by age in the matched cohort (p = .17). Treatment interruption due to irAE at 6 weeks was more common in patient ≥75 years (vs. Conclusion In this cohort of patients with aNSCLC treated in routine clinical practice with PD-1 Ab, immune-toxicity and observed survival were similar amongst age groups.

e20506 Background: In clinical trials, Pem improves overall survival (OS) compared to chemotherapy in a subset of patients (pts) with aNSCLC. Immune related adverse events (irAE) have correlated with improved OS in some studies. We explored efficacy and safety of Pem in a provincial population. Methods: aNSCLC pts treated with Pem between 06/2015 and 08/2018 at BC Cancer were retrospectively identified. Kaplan-Meier curves of OS from initiation of Pem were plotted and multivariable analysis (MVA) was performed with Cox proportional hazard regression models. 3, 6, and 9 month landmark Kaplan-Meier analysis was performed and log-rank tests used to determine the association of irAE subtypes with OS. Multivariable logistic regression models for irAE within 3 months of Pem initiation were also fit. Results: Characteristics of the 190 pt cohort: median age 70y (41-91), ECOG PS 2/3 at start of Pem: 34.2%, squamous histology: 22.1%, EGFR mutation: 3.7%, brain (13.7%) or liver (8.9%) metastases, PD-L1 expression ≥ 50%: 92.6%, treatment line: 1st/ ≥2nd: 74.2%/25.8%. Median cycles delivered 7 (range 1-35). With median survival follow-up of 6.1 months (range 0.03-39.8 months) and 43% pts decreased, median OS of Pem in the 1st line and ≥2nd line settings were 24.3 months (95% CI, 9.7-not reached, NR) and 13.4 months (95% CI, 8.1-NR), respectively. Pts with ECOG PS 2/3 had lower OS vs. ECOG PS 0/1 (5.8 months vs. 16.7 months, log-rank p < 0.0001). On MVA, only ECOG PS (p < 0.001) was associated with OS. 66 pts (34.7% of cohort) experienced 89 irAE; most common irAE: dermatitis (20pts), hypothyroidism (13pts), and pneumonitis (10pts). 8.4% of cohort developed grade 3 or 4 irAE; no grade 5 irAE. The odds of a grade ≥ 3 irAE within 3 months was 6.3 fold higher if ECOG 2/3 vs. 0/1 (p = 0.05). A weak association between pneumonitis and decreased OS at 9 month landmark (p = 0.09) was seen; otherwise no association with irAE subtypes at 3, 6, and 9 month landmarks was observed. Conclusions: In the whole cohort, clinical efficacy and toxicity of Pem was consistent with registration trials. Pts with ECOG PS 2/3 had a significantly lower OS and higher odds of developing grade ≥ 3 irAE than those with good ECOG PS 0/1.

Just over a decade ago, gastrointestinal tumours were a poorly understood mesenchymal neoplasm unsuccessfully treated with chemotherapy. Cytotoxic therapy for advanced disease yielded response rates of 10% and median survival of just 18 months. However, the discovery of KIT and platelet derived growth factor receptor alpha ( PDGFRA) mutations as oncogenic drivers of most gastrointestinal tumours, paved the way for targeted therapy. Imatinib mesylate, a tyrosine kinase inhibitor, produces a clinical benefit rate (complete response, partial response, and stable disease) of more than 80% in metastatic setting and a median survival of 57 months. Imatinib is now also approved in adult patients following resection of KIT-positive GIST. Major insights into the mechanism of action of imatinib, unique pharmacokinetics, drug resistance, and management of low grade but chronic adverse effects continue to be made.

260 Background: In advanced NSCLC, clinical trials have shown significant benefits to pembrolizumab (P) and nivolumab (N). At BC Cancer, clinicians utilize protocol based algorithms to manage immune related adverse events (irAE). The incidence of irAE and efficacy of PD-1 Ab in everyday practice might differ from clinical trials. Methods: Advanced NSCLC patients (pts) treated with N or P between 11/2015 to 10/2017 at BC Cancer were identified. Demographic, tumor, treatment details, and frequency and grade (Gr, CTCAE v4.0) of irAE, were abstracted. Kaplan-Meier curves of median overall survival (OS) from initiation of PD-1 Ab were generated. Multivariable analysis (MVA) with 6-week landmark analysis was performed with Cox proportional hazard regression models. Results: Characteristics of cohort (230 N- and 41 P- treated): median age 64y (range 39-82), non-squamous histology 75%, ECOG PS > 1 at start of PD-1 Ab 31%, brain metastases (mets) 13%, liver mets 12%, and median Charlson Comorbidity Index (CCI) score 6. One hundred sixteen pts experienced 169 separate irAE: Gr1(74), Gr2 (68), Gr3(13), Gr4(10), Gr 5(4). Pneumonitis (14.6% vs. 4.8%, p = 0.041) and arthralgias (12.2% vs. 3.5%, p = 0.044) were more common in P than N. Steroids were administered to 25.2% of N pts and 19.5% of P pts (p = 0.557). Median follow-up from initiation of PD-1 Ab was 8.1months (range 0.1-33.9); median OS (95% CI) for N was 9.2 months (7.75-12.4) and for P was 13.5 months (10.6-not reached). 6-week landmark MVA for whole cohort revealed that male sex (p = 0.051), CCI≥3 (p < 0.001), ECOG PS > 1 (p < 0.001), liver mets (p = 0.017) and development of irAE > Gr2 versus no irAE (p = 0.036) were associated with decreased OS. Age, smoking status, histology, brain mets, EGFR status, irAE Gr 1/2 versus no irAE, and type of PD-1 Ab were not significant. Conclusions: Severe irAE were rare; pneumonitis and arthralgias were more common in P- than N- treated patients. The association with CCI, ECOG PS, and liver mets with decreased OS are consistent with literature. Association of severe irAE with shorter OS might reflect the need for improved physician education in irAE treatment algorithms.

Rates of metastatectomy vary among patients with liver-only metastatic colorectal cancer (MCRC). This study describe predictors of referral to a hepatobiliary surgeon (HBS) and hepatic resection in a population-based setting. Patients referred to the British Columbia Cancer Agency (BCCA) with synchronous or relapsed MCRC isolated to the liver in 2002–2004 were identified. Classification of tumor burden as “high” or “low” was based on prognostic features defined by LiverMetSurvery registry. Metastases larger than 5 cm, bilobar, or more than 3 metastases were classified as high tumor burden. Multivariate logistic regression models were used to identify predictors of HBS referral and subsequent metastatectomy. Overall survival was calculated by the Kaplan–Meier method. Of 618 patients with isolated hepatic metastasis, 148 (24%) were referred to a HBS and 99 (16%) underwent resection. Advanced age was the most common reason for not referring 64 patients (10%) with ECOG performance status 0/1 and low tumor burden. In multivariate analysis, variables associated with referral were younger age (P

6033 Background: Evidence-based guidelines consistently recommend AT for stage III CC but AT is not routinely recommended for stage II CC. Actual practice of the evidence varies. The aim of this re...