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153 Background: Oxaliplatin is a backbone cytotoxic treatment for mCRC patients, particularly in the front-line setting. In the refractory disease, current treatment options are scarce and with limited efficacy. Several retrospective studies have explored the efficacy of oxaliplatin reintroduction/rechallenge (OxRe) in this scenario. However, more evidence is still needed to determine which patients do benefit from this treatment strategy. Methods: The discovery cohort includes all patients treated with oxaliplatin in a third- or fourth-line setting at VHIO between 2015 and 2021 (N = 102). Results were externally validated in a real-world cohort of patients treated at community oncology practices from Oncoclínicas Group in Brazil (N = 157). We analyzed the impact of clinical-molecular features in uni- and multivariable prognostic models in terms of median progression free survival (mPFS) (discovery cohort) and median time to treatment discontinuation (mTTD) (validation cohort). For both cohorts separately, data was extracted from EHRs in structured formats (demographics, tumor characteristics, pharmacy records) and combined with elements from unstructured sources (physician notes on progression and survival status) using technology-based abstraction techniques. Results: In the discovery cohort, 102 out of 735 mCRC patients (13,9%) were eligible. Median oxaliplatin-free interval (from Oxl stop to OxRe) was 17 months (CI95% 13.0-23.2). In OxRe setting, mPFS was 4.0 months (CI95% 3.29-5.03). In PFS multivariate analysis, determinants of favorable outcome were left tumor location (p = 0.01), oxaliplatin-free interval (p = 0.03), administration of Bev in refractory setting (p = 0.001), and not receiving Bev in first-line treatment (p = 0.008). Overall, 27% of all patients had a mPFS > 6 months with OxRe. In the validation cohort, out of 4,317 patients with mCRC, 157 (4%) were treated with OxRe. Median oxaliplatin-free interval was 15 months. Median time to treatment discontinuation (mTTD) of the OxRe was 3.4 months (CI95% 2.8-4.2). In multivariable model, the only independent prognostic factor was addition of Bev to OxRe (p = 0.036). Interestingly, 31% of all patients had mTTD > 6 months, largely enriched (65%) in patients with first Bev exposure at the time of OxRe. Conclusions: This study suggests that in refractory mCRC patients re-exposed to oxaliplatin-based chemotherapy, the addition of Bev is associated with improved outcomes. One-third of the patients are long-term responders (PFS/TTD > 6 months), reinforcing the value of this strategy in selected populations and the relevance of anti-angiogenic agents in refractory mCRC.

55 Background: Right-sided metastatic colorectal cancer (mCRC) has a worse prognosis and the best first-line treatment is still uncertain. The aim of this study was to analyze progression-free survival (PFS) and overall survival (OS) comparing triplet versus doublet backbone chemotherapy in first-line setting for right-sided mCRC. Methods: Retrospective study evaluating 510 patients with mCRC who were treated in a private institution in Brazil from January 2011 to December 2019. Information of 118 patients with right-sided primary tumor was analyzed in this study. Demographic and clinical data were retrieved from electronic medical records. PFS and OS were calculated in months (m) using propensity-score weighting analysis (PSWA) due to expected disparity between the number of patients treated with triplet and doublet regimens. Variables used to balance patient groups were age; metastasectomy; primary tumor resection; bevacizumab use; BRAF and RAS mutation status. Results: The median follow-up was 31 months. Our population was mostly composed of elderly (64%) and female (52%) patients. First-line treatment with triplet backbone chemotherapy was done in 16 patients (14%). Primary tumor resection was done in 14% of the cases, 55% underwent metastasectomy, and 57% received anti-VEGF treatment. BRAF mutation was found in 9% of the patients and RAS mutation in 46%. After PSWA we found a significant better median PFS among patients treated with triplet regimen: 12.7m versus 8.9m compared to those receiving doublet backbone chemotherapy, with a hazard ratio of 0.64 (CI 95%: 0.42 – 0.97); p-value: 0.037. No significant difference was found in OS (29.8m versus 45.5m) between triplet and doublet therapy groups, respectively. Conclusions: In our study we found a significantly better PFS with triplet backbone chemotherapy in first-line setting for right-sided mCRC, encouraging the use of this regimen in treatment-naive selected patients. However, no difference in OS was found, probably due to subsequent treatments. PSWA is an acceptable and needed tool to enable retrospective real world studies involving treatments with expected uneven distribution. More studies are needed to answer the best strategy to target right-sided mCRC, which remains a challenge for oncologists, with unmet needs.

58 Background: Regorafenib and trifluridine/tipiracil (TAS-102) are the only therapeutic options for patients with chemorefractory metastatic colorectal cancer (mCRC) with demonstrated benefit in overall survival (OS). However, they are not accessible worldwide. In Brazil, they have been recently approved, but they have not yet been provided by public health system or private health insurances. We aimed to describe the treatment patterns and clinical outcomes of that population in a setting with limited access to those drugs. Methods: Retrospective study evaluating 510 patients with mCRC who were treated at five Oncoclinicas centers in Brazil from January 2011 to December 2019. Demographic and clinical data were retrieved from electronic medical records. The median OS was calculated by Kaplan-Meier method and prognostic factors were evaluated via multivariable Cox Regression, calculating the Hazard Ratio (HR) and the confidence interval (CI95%). Results: A total of 163 patients (33% of the overall population) received third-line and 73 (15%) fourth-line systemic therapy. Median age was 62 years, 59% were male. Tumors were right-sided in 19%, RAS mutated 44%, BRAF mutated 3%, and high-frequency microsatellite instability 3%. Metastasectomy prior to third-line was performed in 62% of the patients. From the start of third-line therapy, median follow-up was 9.0 months, with 67% of deaths, and median OS was 13.7 months (CI95% 11.8m–20.0m). Most adopted regimens in third-and fourth-line were (1) rechallenge with oxaliplatin-based therapy (39% and 26%, respectively); (2) rechallenge with irinotecan-based therapy (32% and 34%); (3) rechallenge with anti-EGFR monoclonal antibodies (20% and 29%); (4) regorafenib (13% and 25%); and (5) TAS-102 (2% and 4%). In multivariable model including clinical and molecular variables, prior metastasectomy was the only significant prognostic factor for OS (HR 0.51, CI95% 0.31–0.83, p=0.007). Conclusions: In real-world, a meaningful proportion of patients with mCRC are eligible for third and later lines of therapy. Rechallenge with chemotherapy and anti-EGFR agents is overused in a setting of limited access to therapies with demonstrated OS benefit, such as regorafenib and TAS-102. Barriers to drug access impair the adoption of the best evidence-based continuum of care and strategies to overcome them are urgently needed. Refractory patients in later lines of therapy derive survival benefit from prior metastasectomy.

1558 Background: COVID-19 is a challenge for clinical decision-making in cancer patients and the allocation of healthcare resources. An accurate prognosis prediction to effectively triage patients is needed, especially in the community oncology practice. Methods:Nationwide cohort from Oncoclínicas Brazil was used to validate previously developed multivariable logistic regression (mLR) model (Ferrari et al, JCO GO 2021) and to construct a machine learning Random Forest (RF) algorithm as predictor of 30-day mortality after SARS-CoV-2 detection by RT-PCR in cancer patients diagnosed in an outpatient setting. To find the most important baseline clinical determinants of early COVID-19-related death via Gini index, a RF with 100,000 trees was trained in 75% of the dataset, and the performance was assessed in the remaining 25%. We then compared the accuracy of different models in terms of sensitivity, specificity and area under the receiver operating characteristics curves (AUC). Results:From March to December 2020, 533 patients with COVID-19 were prospectively registered in the database. Median age was 60 years (19-93) and 67% were female. Most frequent cancers were breast in 34%, hematological in 16%, and gastrointestinal in 15%. Comorbidities were common (52%), as was current/former smoking history (17%). Most patients were on active systemic therapy or radiotherapy (84%) in the advanced or metastatic disease setting (55%). The overall mortality rate was 15% (CI95% 12%-18%). We validated the original mLR model trained in the first 198 patients: management in a non-curative setting (odds ratio [OR] 3.7), age ≥ 60 years (OR 2.3), and current/former smoking (OR 1.9) were significant predictors of death in the expanded cohort. Presence of comorbidities (OR 1.9) also defined poor outcome in the updated mLR model, which yielded low sensitivity (74%), specificity (68%) and AUC (0.78). With RF modeling, the most significant predictors of 30-day death after COVID-19 (in decreasing order) were older age, treatment of advanced or metastatic disease, tumor type (respiratory tract, brain and unknown primary cancers had higher mortality), COVID-related symptom burden at baseline evaluation and treatment regimen (immunotherapy combinations had higher mortality). The RF model demonstrated high sensitivity (89%), specificity (88%) and AUC (0.96). Conclusions:The results highlight the possibility that machine learning algorithms are able to predict early mortality after COVID-19 in cancer patients with high accuracy. The proposed prediction model may be helpful in the prompt identification of high-risk patients based on clinical features alone, without having to wait for the results of additional tests such as laboratory or radiologic studies. It can also help prioritize medical resources and redefine vaccination strategies. A web-based mortality risk calculator will be created for clinical decision support.

e16631 Background: ICIs have ushered a new era in cancer therapy, but their efficacy in HCC is uncertain. Single-arm phase II studies with sorafenib-refractory patients have suggested clinical activity of nivolumab and pembrolizumab, which have become FDA-approved therapies. Nevertheless, the overall effect of ICIs compared with the standard of care (SOC) in unresectable HCC patients is still unknown. Methods: We systematically searched PubMed, Cochrane Library, Web of Science, LILACS, and ASCO and ESMO Meeting Proceedings in the last 10 years for RCTs that have compared the efficacy of ICIs versus the SOC in the systemic therapy of unresectable HCC. Outcomes of interest included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3-4 treatment-related adverse events (TRAEs). A summary hazard ratio (HR) of OS and PFS was calculated using 95% confidence intervals (CI) by fixed-effects model. The likelihood of ICIs being associated with ORR and TRAEs was expressed by odds ratio (OR) and 95% CI using a random-effects model (PROSPERO ID 162599). Results: Of the 2,334 studies yielded by the search, 3 studies were retained (KEYNOTE-240, CheckMate-459, and IMbrave150), totaling 1,657 patients (985 ICIs versus 672 SOC). Two studies compared ICIs versus sorafenib in 1st line setting, and one study compared with placebo in 2nd line. The ICIs studied were pembrolizumab, nivolumab, and atezolizumab. RCTs with anti-CTLA4 have not been reported. Two studies evaluated ICIs as monotherapy, and one study investigated the association with bevacizumab. Compared with the SOC (sorafenib in 1st line or placebo in 2nd line), ICIs significantly improved OS (HR: 0.78, 95% CI 0.68 – 0.89, p = 0.0002), PFS (HR: 0.79, 95% CI 0.71 – 0.89, p < 0.0001), and ORR (OR: 2.82, 95% CI 2.02 – 3.93, p < 0.0001). ICIs were associated with a lower probability of grade 3-4 TRAEs when compared to sorafenib (OR: 0.44, 95% CI 0.20 – 0.96, p = 0.04). No significant heterogeneity was found among studies when OS and ORR were analyzed, but it was found in the analysis of PFS and TRAEs. Conclusions: ICIs demonstrated superior efficacy and safety compared to the standard therapy of patients with unresectable HCC. The analysis of ICIs as monotherapy and combination therapy increased the heterogeneity among studies. The association of anti-angiogenic therapy with ICIs improved the survival benefit of immunotherapy and should become the new SOC in the 1st line systemic therapy of unresectable HCC.

151 Background: Perioperative CT and resection of CLM are potentially curative therapies in the management of metastatic colorectal cancer (mCRC). Retrospective studies suggest that preoperative bevacizumab increases pathologic response, which is a surrogate endpoint for overall survival (OS). We conducted the first systematic review and meta-analysis addressing the effect of bevacizumab on pathologic response to preoperative therapy of CLM. Methods: We systematically searched PubMed, Cochrane Library, Embase and LILACS from January/2004 to August/2019 for studies that have compared the pathologic response to CT plus bevacizumab versus CT alone as preoperative therapy of potentially resectable CLM. The primary endpoint was pathologic complete response (pCR). Secondary endpoint was major response (MaR) (0-50% residual cancer cells or tumor regression grade (TRG) 1-3 in liver specimen). The likelihood of preoperative therapy being associated with pCR or MaR has been expressed by odds ratio (OR) and 95% confidence intervals (CI) using a random-effects model. Results: Of the 1,319 studies yielded by the search, 9 studies were retained, totaling 1,202 patients (516 CT plus bevacizumab versus 686 CT alone). The addition of bevacizumab to CT increased the pCR rate, but it did not reach statistical significance (OR: 1.24, 95% CI 0.81 – 1.92, p = 0.32). However, MaR was significantly superior in the bevacizumab group (OR: 2.20, 95% CI 1.47 – 3.29, p < 0.001). A higher percentage of patients have been submitted to oxaliplatin-based regimens in bevacizumab group compared to CT alone group (84% versus 68%, p < 0.001), while irinotecan-based regimens have been more common in the CT alone group (11% versus 28%, p < 0.001). Conclusions: The addition of bevacizumab to preoperative CT was associated with higher rates of pathologic response in liver resection of CLM. Anti-angiogenics might potentially improve the recurrence-free survival and OS in the management of potentially resectable CLM and should be evaluated as preoperative therapy in randomized clinical trials.

e15060 Background: Microsatellite stable (MSI-S) RS mCRC patients (pts) have a worse prognosis relative to left sided tumors for overall survival (OS). The present analysis aims to test the hypothesis that a triplet-regimen is superior compared to doublet-regimens (DR; FOLFOX or FOLFIRI) for OS. Methods: Pts with treatment-naive RS mCRC at MD Anderson Cancer Center between January/2011 to December/2018 were selected. We compared the progression-free survival (PFS) and OS of mCRC pts treated with FOLFOXIRI versus DR. Pts treated with anti-EGFR therapy were excluded. Results: A total of 37 pts were treated with FOLFOXIRI and 111 pts with DR. There were no statistical difference between groups regarding gender, KRAS and BRAF mutations, peritoneal metastasis and bevacizumab use. There were statistical difference in age (median: 46y vs 59y) and metastasectomy rates (14% vs 32%) (p < 0.001). KRAS mutation was found in 65% of the population. Median follow-up was 55.3m. Median PFS was 6.5m vs 11.2m (HR: 1.30 95% CI 0.85 – 1.99) and median OS was 17.0m vs 26.3m (HR: 1.01 95% CI 0.60 – 1.68). By univariate analysis, pts who have undergone metastasectomy had superior PFS (14.9m vs 9.2m; p

e14599 Background: The human EGFR family is involved in the pathogenesis and progression of several solid tumors. However, there is no consensus about the prognostic role of HER2 expression and of other members of EGFR family in gastric cancer patients. The aim of this study was to evaluate the prognostic value of members of the EGFR family in gastric cancer. Methods: Retrospective study with 201 patients with gastric and esophagogastric junction (EGJ) adenocarcinoma stages 0 to IV (AJCC 6th edition) who underwent primary tumor resection between January 2006 and December 2008 at Barretos Cancer Hospital, Barretos, São Paulo, Brazil. Tissue from primary tumors were analyzed by tissue microarray technology. IHC scores 0 and 1+ were classified as negative and scores 2+ and 3+ as positive, both for membrane and cytoplasmic expression of HER1, HER2, HER3 and HER4. The HER2 scoring system for gastric cancer was used for classification. Correlations between receptor expression and clinicopathological characteristics were performed according to the chi-square test. Survival analysis was calculated according to a parametric Weibull model with a mixture model incorporating long-term survivors. Multivariate analysis of prognostic factors was performed by a regression model incorporating long-term survivors with the Weibull distribution. Results: Membrane expression of HER1, HER2 and HER4 were 9%, 17% and 15%, respectively. No membrane expression of HER3 was observed. Cytoplasmic expression of HER1, HER3 and HER4 were 45%, 62% and 24%, respectively. Expression of HER2 and HER3 correlated with intestinal-type histology (p: 0.001 and p < 0.001, respectively) and advanced age (p: 0.011 and p: 0.008, respectively). According to a regression model adjusted for age, surgical radicality, surgical modality, Laurén histology, adjuvant therapy, TNM stage and receptors expressions, only TNM stage showed prognostic influence. Conclusions: Expression of HER2 and other members of EGFR family did not have influence on the overall survival in the gastric cancer population studied. The elaboration of a systematic review with meta-analysis or a prospective study could help elucidate this controversial issue.