Background. Colorectal cancer (CRC) is the fourth most deadly cancer worldwide. Unfortunately, a quarter of the patients are diagnosed at late stages, when surgical options are limited. Targeted therapies, particularly immune-checkpoint inhibitors (ICIs), are the latest addition and have been studied herein regarding their efficacy outcomes. Methods. Clinical studies were identified through the PubMed, Scopus and Cochrane databases. Any trial that evaluated ICIs in patients with metastatic CRC (mCRC) and reported the objective response rate was deemed eligible. Data analysis was performed by employing the random-effects model in STATA v.17. Results. A total of 461 articles were identified; 13 clinical trials were included, encompassing a total cohort of 1209 patients. Our study determined that a single PD-1/PD-L1 checkpoint blockade provides durable clinical response in mCRC patients with high microsatellite instability (MSI-H). The combinatorial therapy of CTLA-4 + PD-1 inhibitors also showed high response rates in pre-treated MSI-H patients. The single-arm REGONIVO trial reported durable clinical response in patients with microsatellite stable (MSS) status. Conclusions. Our study surmises that PD-1/PD-L1 inhibitors as well as combination therapy with CTLA-4 and PD-1 inhibitors show encouraging response rates in mCRC patients, albeit exclusively in patients with cancer that are of MSI-H status. A single study suggests that nivolumab + regorafenib can reach a durable response rate in MSS patients; however, further studies in larger randomized settings are required.

Background: The recent implementation of immune-checkpoint inhibitors (ICIs) has markedly changed the management and clinical outcomes for patients with advanced non-small cell lung cancer (NSCLC). Despite higher efficacy, ICIs are associated with a range of immune-related adverse events (irAEs). This retrospective study aimed to investigate the incidence of ICI-related transaminitis/hepatitis in NSCLC patients as well as to establish if any pre-treatment clinical parameters can predict the onset of liver toxicity. Methods: We examined medical records of N=420 NSCLC patients treated across two health districts in Sydney, Australia between 2016 to 2020. R packages (corrplot and ggcorrplot) were used to construct correlation matrices and to calculate the correlation p-value using Spearman method. Logistic regression models were used to determine association of clinical parameters with elevated LFTs. Results: N=185 patients were considered eligible. n=37 (20%) had elevation of liver transaminases at any stage post-ICI commencement, although only n=10 were deemed as those having ICI-related hepatitis. Most of these patients (n=29 [78%]) developed elevated LFTs within 3 months post-therapy initiation. Regression model established that pre-treatment ratio of serum protein (SP) to total bilirubin (TB) showed significant association with the elevated transaminases. Moreover, most of the patients (n=34 [94%]) with elevated LFTs had SP/TB<4. Using a second cohort of melanoma patients, the linear regression model did not establish a significant association between the SP/TB ratio and elevated LFTs. Nonetheless, n=31 (70.5%) patients with immune-mediated transaminitis in the melanoma cohort had SP/TB<4. Conclusion: Our study has established a clinical risk factor associated with the elevation of LFTs in NSCLC patients, thus potentially enabling their prediction at the pre-treatment stage. However, its predictive accuracy was not confirmed in melanoma patients, stressing that ‘ one size does not fit it all ’ when developing predictive scores for irAEs in different patient cohorts.