Numerous targeted therapies have been evaluated for the treatment of non-small cell lung cancer (NSCLC). To date, however, only a few agents have shown promising results. Recent advances in cancer immunotherapy, most notably immune checkpoint inhibitors (ICI), have transformed the treatment scenario for these patients. Although some patients respond well to ICIs, many patients do not benefit from ICIs, leading to disease progression and/or immune-related adverse events. New biomarkers capable of reliably predicting response to ICIs are urgently needed to improve patient selection. Currently available biomarkers—including programmed death protein 1 (PD-1) and its ligand (PD-L1), and tumor mutational burden (TMB)—have major limitations. At present, no well-validated, reliable biomarkers are available. Ideally, these biomarkers would be obtained through less invasive methods such as plasma determination or liquid biopsy. In the present review, we describe recent advances in the development of novel soluble biomarkers (e.g., circulating immune cells, TMB, circulating tumor cells, circulating tumor DNA, soluble factor PD-L1, tumor necrosis factor, etc.) for patients with NSCLC treated with ICIs. We also describe the potential use of these biomarkers as prognostic indicators of treatment response and toxicity.

The role of Kirsten rat sarcoma viral oncogene homolog (KRAS) and neuroblastoma RAS viral oncogene homolog (NRAS) mutations as negative predictors for anti-epidermal growth factor receptor (EGFR) therapies in metastatic colorectal cancer (CRC) has been firmly established. However, whether the RAS mutation status plays a role as a biomarker for anti-vascular endothelial growth factor (VEGF) treatment remains controversial. Data from 93 CRC patients who received first-line cytotoxic chemotherapy with fluoropyrimidines and oxaliplatin, with or without bevacizumab, were analyzed. We investigated the association between the RAS mutation status and clinical outcomes in terms of response rate, progression-free survival (PFS) and overall survival (OS). Mutations in RAS genes were observed in 47 (52.6%) patients (45 KRAS and 2 NRAS mutations). Patients with tumours harbouring RAS mutations were less suitable for primary tumour resection, were more likely to develop lung metastases, and received bevacizumab treatment for a shorter time period compared with those with wild-type tumours. The response rate to chemotherapy did not differ according to the RAS mutation status, and there were no significant differences in PFS [RAS mutation: 12 months, 95% confidence interval (CI): 8.7–15.2 vs. RAS wild-type: 12 months, 95% CI: 9.67–14.32; P=0.857] or OS (RAS mutation: 20 months, 95% CI: 14.3–25.6 vs. RAS wild-type: 24 months, 95% CI: 18.7–29.2; P=0.631). Patients with RAS mutation vs. those with RAS wild-type exhibited a favourable trend in PFS when treated with bevacizumab (13 months, 95% CI: 6.5–19.4 vs. 10 months, 95% CI: 4.2–15.7, respectively; P=0.07) and OS (27 months, 95% CI: 18.5–35.4 vs. 15 months, 95% CI: 12.4–17.5, respectively; P=0.22). In conclusion, RAS mutations are not a prognostic marker for PFS and OS in CRC patients receiving fluoropyrimidine-oxaliplatine treatment, with or without bevacizumab. RAS mutations are not predictive of the lack of efficacy of bevacizumab, and these patients appear to benefit from anti-angiogenic treatment.

Background: Studies of patients with cancer affected by coronavirus disease 2019 (COVID-19) are needed to assess the impact of the disease in this sensitive population, and the influence of different cancer treatments on the COVID-19 infection and seroconversion. Material and Methods: We performed a retrospective analysis of all patients hospitalized with RT-PCR positive for COVID-19 in our region to assess the prevalence of cancer patients and describe their characteristics and evolution (Cohort 1). Concurrently, a transversal study was carried out in patients on active systemic cancer treatment for symptomatology and seroprevalence (IgG/IgM by ELISA-method) against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) (Cohort 2). Results: A total of 215 patients (Cohort 1) were admitted to hospital with a confirmed COVID-19 infection between February 28 and April 30, 2020, and 17 died (7.9%). A medical record of cancer was noted in 43 cases (20%), 6 of them required Intensive care unit ICU attention (14%), and 7 died (16%). There were thirty-six patients (83%) who tested IgG/IgM positive for SARS-CoV-2. Patients on immunosuppressive therapies presented a lower ratio of seroconversion (40% vs. 8%; p = 0.02). In Cohort 2, 166 patients were included in a symptoms-survey and tested for SARS-CoV-2. Any type of potential COVID-19-related symptom was referred up to 67.4% of patients (85.9% vs. 48.2% vs. 73.9%, for patients on chemotherapy, immunotherapy and targeted therapies respectively, p < 0.05). The seroprevalence ratio was 1.8% for the whole cohort with no significant differences by patient or treatment characteristics. Conclusion: Patients with cancer present higher risks for hospital needs for COVID-19 infection. The lack of SARS-CoV-2 seroconversion may be a concern for patients on immunosuppressive therapies. Patients receiving systematic therapies relayed a high rate of potentially COVID-19-related symptoms, particularly those receiving chemotherapy. However, the seroconversion rate remains low and in the range of general population.

Current treatment landscape for oligometastatic non-small cell lung cancer

E15094 Background: CC is a heterogeneuous disease with clinical, pathological and biological variability. Molecular classification could indentify prognostic subtypes. Methods: 105 patients with stage I-III were included in the study. KRAS, NRAS (Exons 2,3,4) and BRAFV600E mutations were analyzed by a PCR-based assay. MMR (MLH1 and MSH2) proteins expression were analyzed by immunohistochemistry; loss of expression of any indicated deficient (dMMR) vs proficient MMR (pMMR). CC was categorized into 5 subtypes: Traditional (T) (pMMR; wt BRAF and RAS); Alternate (A) (pMMR; wt BRAF and mutant RAS); Serrated (S) (pMMR; mutant BRAF and wt RAS); Serrated dMMR (Sd) (dMMR; mutant BRAF and wt RAS) and Familial (F) (dMMR; wt BRAF, any RAS). Non-parametric tests were used for correlation with clinico-pathological variables and Cox models for association with Disease Free Survival (DFS). Results: Mutational status: 41% KRAS, 5% NRAS and 11% BRAF mutations. MMR status: dMMR 19%; pMMR 81%. Molecular subtypes: T 35%, A 39%, S 7%, Sd 5% and F 14%. Right-sided CC 46%; high grade (HG) CC 12%. Right-sided and dMMR CC showed higher rate of BRAF mutations (21% vs 4% p = .011 and 25% vs 8% p = .034). Stage II and III CC showed higher rate of BRAF mutations vs stage I (14% and 21% vs 0%, respectively; p < .005). dMMR CC was more often right-sided (85% vs 37%, p < .001) and had more HG histology (31% vs 8%, p = .006). T subtype vs others was more likely left-sided (78% vs A 55% vs S 28% vs Sd 0% vs F 20%; p < 0.005). S dMMR and F vs A were more likely right-sided (100% and 80 % vs 45 %; p < .05). F vs T and vs A CC had more HG (33% vs 8%, p = .039; vs 7%, p = .026). Risk of progression is higher in mutated KRAS CC (Odds ratio (OR) 3,36; CI: 1,19-9,47 p = .017). RAS mutated CC showed higher risk of death (OR 5,11; CI: 1,00-25,43 p = .040). Wt KRAS and wt RAS CC showed better DFS (HR 0,31 CI 0.12-0.79 p = .015 and HR 0,39 CI 0,15–1,00 p = .051). T vs S showed better DFS (HR 0,21 IC 0,04 – 0,95 p = .044). S and A together compared to T, showed a tendency to a worse DFS (HR 2,86 IC 0,93–0,78 p = .066). Conclusions: This molecular classification identifies prognostic groups with different clinical and pathological features in early-stage CC.