Systemic Inflammation Response Index and weight loss as prognostic factors in metastatic pancreatic cancer: A concept study from the PANTHEIA-SEOM trial.

BACKGROUND: The prognostic value of the Systemic Inflammation Response Index (SIRI) in advanced pancreatic cancer is recognized, but its correlation with patients´ nutritional status and outcomes remains unexplored. AIM: To study the prognostic significance of SIRI and weight loss in metastatic pancreatic cancer. METHODS: The PANTHEIA-Spanish Society of Medical Oncology (SEOM) study is a multicentric (16 Spanish hospitals), observational, longitudinal, non-interventional initiative, promoted by the SEOM Real World-Evidence work group. This pilot study sought to analyze the association between weight loss and inflammatory status as defined by SIRI. The cohort stems from a proof-of-concept pilot study conducted at one of the coordinating centers. Patients with pathologically confirmed metastatic pancreatic adenocarcinoma, treated from January 2020 to January 2023, were included. The index was calculated using the product of neutrophil and monocyte counts, divided by lymphocyte counts, obtained within 15 days before initiation chemotherapy. This study evaluated associations between overall survival (OS), SIRI and weight loss. RESULTS: A total of 50 patients were included. 66% of these patients were male and the median age was 66 years. Metastasis sites: 36% liver, 12% peritoneal carcinomatosis, 10% lung, and 42% multiple locations. Regarding the first line palliative chemotherapy treatments: 50% received gemcitabine plus nab-paclitaxel; 28%, modified fluorouracil, leucovorin, irinotecan and oxaliplatin, and 16% were administered gemcitabine. 42% had a weight loss > 5% in the three months (mo) preceding diagnosis. 21 patients with a SIRI ≥ 2.3 × 103/L exhibited a trend towards a lower median OS compared to those with a SIRI < 2.3 × 103/L (4 vs 18 mo; P < 0.000). Among 21 patients with > 5% weight loss before diagnosis, the median OS was 6 mo, in contrast to 19 mo for those who did not experience such weight loss (P = 0.003). Patients with a weight loss > 5% showed higher SIRI levels. This difference was statistically significant (P < 0.000). For patients with a SIRI < 2.3 × 103/L, those who did not lose > 5% of their weight had an OS of 20 mo, compared to 11 mo for those who did (P < 0.001). No association was found between carbohydrate antigen 19-9 levels ≥ 1000 U/mL and weight loss. CONCLUSION: A higher SIRI was correlated with decreased survival rates in patients with metastatic pancreatic cancer and associated with weight loss. An elevated SIRI is suggested as a predictor of survival, emphasizing the need for prospective validation in the upcoming PANTHEIA-SEOM study.

High tumor burden in patients with non-small-cell lung cancer: a Delphi survey among Spanish oncologists.

Aim: To define high tumor burden (HTB) in non-small-cell lung cancer. Methods: A total of five oncologists initiated the project, selecting 66 participants, and elaborated a questionnaire with 26 statements using the Delphi method with a 9-point Likert scale of agreement. Results: Factors with moderate strength of consensus were identified, including a sum of the longest diameter of lesions ≥10 cm, elevated Lactate dehydrogenase, hepatic involvement, lymphangitis carcinomatosis, brain involvement unapproachable with local techniques and pericardial effusion. There was a consensus against increases in tumor markers and asymptomatic brain involvement being related to HTB. HTB was considered a relevant factor for treatment selection supporting the choice of combination regimens versus immunotherapy only. Conclusion: In this Delphi study, experts defined several factors associated with HTB in non-small cell lung cancer.

Complete response to third-line treatment with trifluridine/tipiracil (TAS-102) in stage IV colon adenocarcinoma.

A clinical case of a 61-year-old female diagnosed with stage IV right colon adenocarcinoma (unresectable liver and multiple lymph node metastases at the time of diagnosis), Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma rat sarcoma viral oncogene homolog (NRAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type, proficient mismatch repair (pMMR), in whom a complete response to the third-line of systemic treatment with trifluridine/tipiracil (TAS-102) was obtained. The complete response has been maintained for more than 2 years after its suspension.

One-year efficacy and safety of naloxegol on symptoms and quality of life related to opioid-induced constipation in patients with cancer: KYONAL study.

OBJECTIVES: Naloxegol is a peripherally acting µ-opioid receptor antagonist (PAMORA) for treatment of opioid-induced constipation (OIC). The main objective was to analyse the long-term efficacy, quality of life (QOL) and safety of naloxegol in patients with cancer in a real-world study. METHODS: This one-year prospective study included patients older than 18 years, with active oncological disease who were under treatment with opioids for pain control and Karnofsky≥50 and OIC with inadequate response to treatment with laxative (s). All the patients received treatment with naloxegol according to clinical criteria. The main efficacy objectives were measured by the patient assessment of constipation QOL questionnaire (PAC-QOL), the PAC symptoms (PAC-SYM), the response rate at day 15, and months 1-3-6-12, and global QOL (EuroQoL-5D-5L). RESULTS: A total of 126 patients (58.7% males) with a mean age of 61.5 years (95% CI 59.4 to 63.7) were included. PAC-SYM and PAC-QOL total score and all their dimensions improved from baseline (p<0.0001). At 12 months, 77.8% of the patients were responders to naloxegol treatment. Global QOL was conserved from baseline. A total of 28 adverse reactions, mainly gastrointestinal were observed in 15.1% of the patients (19/126), being 75% (21) mild, 17.9% (5) moderate and 7.1% (2) severe. Most adverse reactions (67.9%) appeared the first 15 days of treatment. CONCLUSION: The results of this first long-term and real-world-data study in patients with cancer, showed the sustained efficacy and safety of naloxegol for the treatment of OIC in this group of patients.

Neoadjuvant immunotherapy for dMMR/MSI-H locally advanced rectal cancer: The future new standard approach?

INTRODUCTION: This is a review of the evidence from studies of the efficacy and tolerability of neoadjuvant immunotherapy for mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) Locally Advanced Rectal Cancer (LARC). METHODS: For this review, we searched EMBASE and MEDLINE until 22 September 2022. The terms used in the search included mismatch repair-deficient, microsatellite instability, rectal cancer, neoadjuvant and immunotherapy. RESULTS: A total of 92 studies were obtained but only 9 were selected for the final analysis (one prospective and eight retrospective studies), including less than 20 patients per study. Neoadjuvant immunotherapy provides overall response rates of 100% (with and completed clinical response between 40 and 100%). CONCLUSION: Our review discusses completed prospective and retrospective studies, ongoing clinical trials, and the clinical practice of using neoadjuvant immunotherapy for MSI-H/dMMR LARC. The promising results obtained, would open the door to exploring other alternatives for these patients, offering the possibility of avoiding chemoradiation therapy and surgery in the future.

High tumor burden in non-small-cell lung cancer: A review of the literature.

Background and Aim: Lung cancer is the leading cause of cancer death worldwide and the majority of the patients have advanced/metastatic disease on presentation. In clinical practice, several biomarkers and clinical factors are taken into account when choosing the best treatment option in advanced non-small-cell lung cancer (NSCLC). One potential marker may be tumor burden (TB). However, this concept is not specifically defined in NSCLC, and usually, it is used as a synonymous for aggressive disease. Methods: A non-systematic literature review was conducted. We searched for eligible randomized controlled trials from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials with a cutoff at February 2021. The keywords included non-small-cell lung cancer, tumor burden, aggressive disease, prognosis biomarker, predictive biomarker, and immunotherapy. Results and Conclusions: This review addresses the definition of TB in advanced NSCLC, the pathophysiology of high TB lesions, and the role of TB as a prognosis biomarker. Relevance for Patients: The concept of aggressive disease, as high tumor burden definition, remains poorly defined and rarely considered in clinical research or clinical practice in oncology. The identification of this subgroup of patients could be interesting for defining and optimizing a more aggressive treatment strategy.

Correction to: SEOM Clinical Guideline update for the prevention of chemotherapy-induced nausea and vomiting (2021)

In this article the title was incorrectly given as “SEOM clinical guideline emesis (2021)” but should have been “SEOM Clinical Guideline update for the prevention of chemotherapy-induced nausea and vomiting (2021).”The original article has been corrected.

New horizons for uncommon mutations in non-small cell lung cancer: BRAF, KRAS, RET, MET, NTRK, HER2.

The 2004 discovery of EGFR mutations, followed by ALK rearrangements, ushered in a targeted therapy era for advanced non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors targeting gene alterations have substantially improved survival and quality of life for patients with NSCLC. In the last decade, rearrangements of the ROS1 oncogene have been incorporated into healthcare practice that are applicable to another small subgroup of patients who benefit from similar targeted strategies. Recent genome studies of lung adenocarcinoma have identified other possible therapeutic targets, including RET, NTRK fusions, c-MET alterations, and activating mutations in KRAS, BRAF, and HER2, all with frequencies greater than 1%. Lung cancers harbouring these genome changes can potentially be treated with agents approved for other indications or under clinical development. This review updates the therapeutic arsenal that especially targets those genes.

SEOM Clinical Guideline update for the prevention of chemotherapy-induced nausea and vomiting (2021)

Among the side effects of anticancer treatment, chemotherapy-induced nausea and vomiting (CINV) is one of the most feared given its high prevalence, affecting up to 40% of patients. It can impair patient’s quality of life and provoke low adherence to cancer treatment or chemotherapy dose reductions that can comprise treatment efficacy. Suffering CINV depends on factors related to the intrinsic emetogenicity of antineoplastic drugs and on patient characteristics. CINV can appear at different times regarding the administration of antitumor treatment and the variability of risk according to the different antitumor regimens has, as a consequence, the need for a different and adapted antiemetic treatment prophylaxis to achieve the desired objective of complete protection of the patient in the acute phase, in the late phase and in the global phase of emesis. As a basis for the recommendations, the level of emetogenicity of anticancer treatment is considered and they are classified as high, moderate, low and minimal emetogenicity and these recommendations are based on the use of antiemetic drugs with a high therapeutic index: anti 5-HT, anti-NK and steroids. Despite having highly effective treatments, clinical reality shows that they are not applied enough, so evidence-based recommendations are needed to show the best options and help in decision-making. To cover all the antiemetic prophylaxis options, we have also included recommendations for oral treatments, multiday regimens and radiation-induced emesis prevention.

Clinical and economic impact of 'ROS1-testing' strategy compared to a 'no-ROS1-testing' strategy in advanced NSCLC in Spain.

BACKGROUND: Detection of the ROS1 rearrangement is mandatory in patients with advanced or metastatic non-small cell lung cancer (NSCLC) to allow targeted therapy with specific inhibitors. However, in Spanish clinical practice ROS1 determination is not yet fully widespread. The aim of this study is to determine the clinical and economic impact of sequentially testing ROS1 in addition to EGFR and ALK in Spain. METHODS: A joint model (decision-tree and Markov model) was developed to determine the cost-effectiveness of testing ROS1 strategy versus a no-ROS1 testing strategy in Spain. Distribution of ROS1 techniques, rates of testing, positivity, and invalidity of biomarkers included in the analysis (EGFR, ALK, ROS1 and PD-L1) were based on expert opinion and Lungpath real-world database. Treatment allocation depending on the molecular testing results was defined by expert opinion. For each treatment, a 3-states Markov model was developed, where progression-free survival (PFS) and overall survival (OS) curves were parameterized using exponential extrapolations to model transition of patients among health states. Only medical direct costs were included (€ 2021). A lifetime horizon was considered and a discount rate of 3% was applied for both costs and effects. Both deterministic and probabilistic sensitivity analyses were performed to address uncertainty. RESULTS: A target population of 8755 patients with advanced NSCLC (non-squamous or never smokers squamous) entered the model. Over a lifetime horizon, the ROS1 testing scenario produced additional 157.5 life years and 121.3 quality-adjusted life years (QALYs) compared with no-ROS1 testing scenario. Total direct costs were increased up to € 2,244,737 for ROS1 testing scenario. The incremental cost-utility ratio (ICUR) was 18,514 €/QALY. Robustness of the base-case results were confirmed by the sensitivity analysis. CONCLUSIONS: Our study shows that ROS1 testing in addition to EGFR and ALK is a cost-effective strategy compared to no-ROS1 testing, and it generates more than 120 QALYs in Spain over a lifetime horizon. Despite the low prevalence of ROS1 rearrangements in NSCLC patients, the clinical and economic consequences of ROS1 testing should encourage centers to test all advanced or metastatic NSCLC (non-squamous and never-smoker squamous) patients.

SEOM clinical guideline emesis (2021).

Among the side effects of anticancer treatment, chemotherapy-induced nausea and vomiting (CINV) is one of the most feared given its high prevalence, affecting up to 40% of patients. It can impair patient's quality of life and provoke low adherence to cancer treatment or chemotherapy dose reductions that can comprise treatment efficacy. Suffering CINV depends on factors related to the intrinsic emetogenicity of antineoplastic drugs and on patient characteristics. CINV can appear at different times regarding the administration of antitumor treatment and the variability of risk according to the different antitumor regimens has, as a consequence, the need for a different and adapted antiemetic treatment prophylaxis to achieve the desired objective of complete protection of the patient in the acute phase, in the late phase and in the global phase of emesis. As a basis for the recommendations, the level of emetogenicity of anticancer treatment is considered and they are classified as high, moderate, low and minimal emetogenicity and these recommendations are based on the use of antiemetic drugs with a high therapeutic index: anti 5-HT, anti-NK and steroids. Despite having highly effective treatments, clinical reality shows that they are not applied enough, so evidence-based recommendations are needed to show the best options and help in decision-making. To cover all the antiemetic prophylaxis options, we have also included recommendations for oral treatments, multiday regimens and radiation-induced emesis prevention.

Analyzing Differences in Perception between Oncologists and Patients to Adapt Pharmacological Treatment for Breakthrough Cancer Pain: Observational ADAPTATE Study.

Background: Transmucosal fentanyl (TF), used for breakthrough cancer pain (BTcP) treatment, has different formulations with distinctive attributes. The hypothesis is that, in shared decision making for the prevention of certain therapeutic problems, doctors and patients assign different value to the characteristics of treatment options. Aim: The aim of this study was to assess the discordance between the oncologists' opinion of attributes of TF and patients' expectations in BTcP treatment. Methods: This is a multicenter, cross-sectional observational study using simultaneous written surveys of doctors and patients suffering from BTcP episodes. The opinion of Spanish oncologists and patients regarding the importance of 14 different attributes of TF treatment (start of action, potency, duration, presentations and doses available, ease of use, titration, administration time, need for saliva, oral mucositis, rhinitis, adverse events, risk of abuse, evidence available, and need for instructions or health personnel to handle the medication), using two surveys, one for each group. Results: Sixty-three clinical oncologists and 272 patients participated in the study. The patients' satisfaction with and knowledge of BTcP treatment was 6.4 and 6.8 points, respectively (scale 1-9). The attributes with the highest relevance were shared by both groups, although their priority differed. Significant differences were observed in the greater importance given by oncologists (onset and duration of analgesia, need for saliva, presence of mucositis, and time required for patient education) and patients (risk of opioid abuse/aberrant behavior). Conclusion: Our results confirm that some aspects that most concern patients about the treatment of BTcP differ from those to which oncologists attach most importance. Increased patient awareness and education about BTcP and its treatment could lead to greater satisfaction and better patient involvement in therapeutic decisions. Certain barriers need to be overcome, such as lack of time in consultations and poor communication skills of oncologists that hinder patient health education.

Efficacy of nintedanib plus docetaxel in patients with refractory advanced epidermal growth factor receptor mutant lung adenocarcinoma

Background Anti-angiogenic agents are reported to exert clinical activity in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). We evaluated the outcomes of the combination of docetaxel plus nintedanib in refractory NSCLC patients harboring EGFR mutations. Methods We retrospectively analyzed 19 patients with advanced EGFR-mutant NSCLC who had progressed to EGFR tyrosine kinase inhibitors (TKI) and platinum-based chemotherapy receiving docetaxel and nintedanib at 14 Spanish institutions from January 2013 to December 2019. Kaplan–Meier and log-rank tests were used to evaluate progression-free survival (PFS) and overall survival (OS). Results Median age was 58.9 years (range 42.8–81), 73.7% were female. All patients were Caucasian, and 73.7% were never or light smokers. The baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0–1 in 94.7% of patients. All patients had adenocarcinoma. Brain and liver metastases were present in 47.4% and 31.6% of patients, respectively. The most common EGFR mutations were exon 19 deletion (52.6%) and exon 21 L858R mutation (36.8%); 47.4% patients presented the EGFR T790M. 94.8% of the patients had received 2–3 previous treatment lines. Docetaxel was administered at 75 mg/m2/3 weeks to 16 patients, at 60 mg/m2 to 2 patients and at 45 mg/m2 to one patient. Nintedanib was given until disease progression or unacceptable toxicity at 200 mg twice daily except in 2 patients who received 150 mg twice daily and one patient who received 100 mg/12 h. With a median follow-up of 11.4 months (1–38), the median PFS was 6.1 months [95% confidence interval (CI), 4.9–7.3] and the median OS 10.1 months (95% CI 5.9–14.3). The objective response rate (ORR) was 44.4% (23.7–66.8%) and the disease control rate (DCR) 72.2% (49.4–88.5%) (AU)

Efficacy of nintedanib plus docetaxel in patients with refractory advanced epidermal growth factor receptor mutant lung adenocarcinoma.

BACKGROUND: Anti-angiogenic agents are reported to exert clinical activity in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). We evaluated the outcomes of the combination of docetaxel plus nintedanib in refractory NSCLC patients harboring EGFR mutations. METHODS: We retrospectively analyzed 19 patients with advanced EGFR-mutant NSCLC who had progressed to EGFR tyrosine kinase inhibitors (TKI) and platinum-based chemotherapy receiving docetaxel and nintedanib at 14 Spanish institutions from January 2013 to December 2019. Kaplan-Meier and log-rank tests were used to evaluate progression-free survival (PFS) and overall survival (OS). RESULTS: Median age was 58.9 years (range 42.8-81), 73.7% were female. All patients were Caucasian, and 73.7% were never or light smokers. The baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0-1 in 94.7% of patients. All patients had adenocarcinoma. Brain and liver metastases were present in 47.4% and 31.6% of patients, respectively. The most common EGFR mutations were exon 19 deletion (52.6%) and exon 21 L858R mutation (36.8%); 47.4% patients presented the EGFR T790M. 94.8% of the patients had received 2-3 previous treatment lines. Docetaxel was administered at 75 mg/m2/3 weeks to 16 patients, at 60 mg/m2 to 2 patients and at 45 mg/m2 to one patient. Nintedanib was given until disease progression or unacceptable toxicity at 200 mg twice daily except in 2 patients who received 150 mg twice daily and one patient who received 100 mg/12 h. With a median follow-up of 11.4 months (1-38), the median PFS was 6.1 months [95% confidence interval (CI), 4.9-7.3] and the median OS 10.1 months (95% CI 5.9-14.3). The objective response rate (ORR) was 44.4% (23.7-66.8%) and the disease control rate (DCR) 72.2% (49.4-88.5%). Efficacy tended to be greater in patients with the acquired T790M who had received osimertinib, with a median PFS of 6.3 (95% CI 2.1-10.5) versus (vs.) 4.8 (95% CI 3.5-6.1) and a median OS of 12.3 months (95% CI 8.6-16.0) vs. 6.7 months (95% CI 3.9-9.4), although this tendency was not statistically significant (p = 0.468 and p = 0.159, respectively). Sixteen patients (84.2%) had a total of 34 adverse events (AEs), with a median of two (0-6) AEs per patient. The most frequent AEs were asthenia (20.6%) and diarrhea (20.6%). One treatment-related death due to portal thrombosis was reported. CONCLUSIONS: Our data indicate that the combination of docetaxel and nintedanib can be considered to be an effective treatment for EGFR TKI-resistant EGFR-mutant NSCLC.

Clinical and economic impact of current ALK rearrangement testing in Spain compared with a hypothetical no-testing scenario.

BACKGROUND: Currently biomarkers play an essential role in diagnosis, treatment, and management of cancer. In non-small cell lung cancer (NSCLC) determination of biomarkers such as ALK, EGFR, ROS1 or PD-L1 is mandatory for an adequate treatment decision. The aim of this study is to determine the clinical and economic impact of current anaplastic lymphoma kinase testing scenario in Spain. METHODS: A joint model, composed by decision-tree and Markov models, was developed to estimate the long-term health outcomes and costs of NSCLC patients, by comparing the current testing scenario for ALK in Spain vs a hypothetical no-testing. The current distribution of testing strategies for ALK determination and their sensitivity and specificity data were obtained from the literature. Treatment allocation based on the molecular testing result were defined by a panel of Spanish experts. To assess long-term effects of each treatment, 3-states Markov models were developed, where progression-free survival and overall survival curves were extrapolated using exponential models. Medical direct costs (expressed in €, 2019) were included. A lifetime horizon was used and a discount rate of 3% was applied for both costs and health effects. Several sensitivity analyses, both deterministic and probabilistic, were performed in order test the robustness of the analysis. RESULTS: We estimated a target population of 7628 NSCLC patients, including those with non-squamous histology and those with squamous carcinomas who were never smokers. Over the lifetime horizon, the current ALK testing scenario produced additional 5060 and 3906 life-years and quality-adjusted life-years (QALY), respectively, compared with the no-testing scenario. Total direct costs were increased up to € 51,319,053 for testing scenario. The incremental cost-effectiveness ratio was 10,142 €/QALY. The sensitivity analyses carried out confirmed the robustness of the base-case results, being the treatment allocation and the test accuracy (sensitivity and specificity data) the key drivers of the model. CONCLUSIONS: ALK testing in advanced NSCLC patients, non-squamous and never-smoker squamous, provides more than 3000 QALYs in Spain over a lifetime horizon. Comparing this gain in health outcomes with the incremental costs, the resulting incremental cost-effectiveness ratio reinforces that testing non-squamous and never-smoker squamous NSCLC is a cost-effective strategy in Spain.

Biomarkers of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer: Beyond PD-L1.

Immunotherapy has markedly improved the survival rate of patients with non-small cell lung cancer (NSCLC) and has introduced a new era in lung cancer treatment. Although some patients achieve durable responses to checkpoint blockade, not all experience such benefits, and some suffer from significant immunotoxicities. Thus, it is crucial to identify potential biomarkers suitable for screening the population that may benefit from immunotherapy. Based on the current clinical trials, the aim of the present study was to review the biomarkers for immune checkpoint inhibition that may have the potential to predict the response to immunotherapy in patients with lung cancer. A non-systematic literature review was done. We searched for eligible randomized controlled trials (RCTs) from PubMed, Embase, and the Cochrane Central Register of Controlled Trials from January 2015 to January 2021. The keywords included biomarkers, immunotherapy, immune checkpoint inhibition, programmed death ligand 1 (PD-L1), and non-small cell lung cancer. Additional biomarkers beyond PD-L1 that have been shown to have predictive capacity include tumor mutational burden, microsatellite instability, lung immune prognostic index, gut microbiome, and certain alterations in genes (eg, STK11 deletion, LKB1 kinase mutation, MDM2/4 amplification) that confer immunoresistance. The biomarkers reviewed in this article could help us better select the appropriate immunotherapy treatment for patients with NSCLC.

Anti-EGFR Antibody Plus Chemotherapy Treatment in a Patient with Synchronous Merkel Cell Carcinoma and Colorectal Cancer.

Merkel cell carcinoma (MCC) is a rare neuroendocrine cutaneous malignancy. During early stages, surgery is the primary treatment followed by radiotherapy in patients at high risk of recurrence. Definitive radiation therapy is an alternative for patients who are not surgical candidates, reserving chemotherapy for metastatic disease. We present a case of a male patient diagnosed with MCC and stage IV colorectal cancer and we focus on the skin tumor shrinkage after specific colorectal cancer treatment.