Evaluation of the Molecular Landscape in PD-L1 Positive Metastatic NSCLC: Data from Campania, Italy.

BACKGROUND: Immune-checkpoint inhibitors (ICIs) have increased and improved the treatment options for patients with non-oncogene-addicted advanced stage non-small cell lung cancer (NSCLC). However, the role of ICIs in oncogene-addicted advanced stage NSCLC patients is still debated. In this study, in an attempt to fill in the informational gap on the effect of ICIs on other driver mutations, we set out to provide a molecular landscape of clinically relevant oncogenic drivers in programmed death-ligand 1 (PD-L1) positive NSCLC patients. METHODS: We retrospectively reviewed data on 167 advanced stage NSCLC PD-L1 positive patients (≥1%) who were referred to our clinic for molecular evaluation of five driver oncogenes, namely, EGFR, KRAS, BRAF, ALK and ROS1. RESULTS: Interestingly, n = 93 (55.7%) patients showed at least one genomic alteration within the tested genes. Furthermore, analyzing a subset of patients with PD-L1 tumor proportion score (TPS) ≥ 50% and concomitant gene alterations (n = 8), we found that n = 3 (37.5%) of these patients feature clinical benefit with ICIs administration, despite the presence of a concomitant KRAS gene alteration. CONCLUSIONS: In this study, we provide a molecular landscape of clinically relevant biomarkers in NSCLC PD-L1 positive patients, along with data evidencing the clinical benefit of ICIs in patient NSCLC PD-L1 positive alterations.

Concurrent chemotherapy alone versus irreversible electroporation followed by chemotherapy on survival in patients with locally advanced pancreatic cancer.

Pancreatic adenocarcinoma is one of the most fatal cancers, characterized by aggressive tumor growth and a short patient survival time between diagnosis and death. Safe and effective treatment options are limited, especially in cases when surgical resection is not possible. Irreversible electroporation (IRE) is a non-thermal ablation technique recently introduced in the treatment of pancreatic cancer. From 2013 to 2016, 29 cases of locally advanced pancreatic cancer (LAPC) treated with IRE were retrospectively analyzed and the median overall survival (OS) rates were compared with patients with the same diagnosis who received standard chemotherapy as reported in the literature. Literature was selected according to a predetermined protocol. Secondarily, preoperative and postoperative Karnofsky scores of the 29 IRE-treated patients were compared to determine improvement in quality-of-life. Median OS of IRE-treated patients was 14 months (SE 11 months, 95% CI range 9.86-18.14). For IRE-treated patients, the Karnofsky score increased from Tzero to T3m by a mean of 28.28 (SE 2.11, 95% CI range 23.95-32.60). In 27 patients, 6-month imaging follow-up showed a mean lesion volumetric decrease percentage of 40.32% (SE 2.76, 95% CI 34.63-46.01%). Treatment with IRE followed by chemotherapy substantially increases median OS rate and quality-of-life of LAPC-diagnosed patients when compared to patients treated with traditional methods, including chemotherapy. Further investigation of this multi-modal treatment is warranted.

Percutaneous CT-guided irreversible electroporation followed by chemotherapy as a novel neoadjuvant protocol in locally advanced pancreatic cancer: Our preliminary experience.

INTRODUCTION: Irreversible electroporation (IRE) is a non-thermal ablation technique recently used in pancreatic cancer. In our prospective study we evaluated safety, feasibility and efficacy of a neoadjuvant protocol based on CT-guided percutaneous IRE followed by chemotherapy in patients with locally advanced pancreatic cancer (LAPC). METHODS: We performed CT-guided percutaneous IRE in 20 patients with LAPC, followed by a combination of gemcitabine (1000 mg/mq) and oxaliplatin (100 mg/mq) biweekly. Imaging follow-up was performed by a contrast enhanced CT scan at 1, 3, 6 months and then every 3 months. RESULTS: No major complications occurred. Two patients died 3 and 4 months after IRE because of rapidly progressive disease. In the remaining 18 patients 6-month imaging follow-up showed a mean lesions volumetric decrease percentage of 42.89% (95% Confidence Interval: 34.90-54.88%). Thanks to lesions downstaging, three patients underwent R0 resection. At last available follow-up (mean follow-up 91 months; range 6-14), imaging showed no disease progression or post-surgical relapse in all 18 cases. The mean estimated survival was 12,950 months (95% CI: 11,570-14,332). CONCLUSIONS: Our preliminary study suggests that IRE followed by chemotherapy is safe, feasible and effective in producing local control of LAPC, with a possible downstaging effect to resectable lesions.

The role of immunotherapy in solid tumors: report from the Campania Society of Oncology Immunotherapy (SCITO) meeting, Naples 2014.

The therapeutic approach to advanced or metastatic solid tumors, either with chemotherapy or targeted therapies, is mainly palliative. Resistance to chemotherapy occurs very frequently and is one of the most important reasons for disease progression. Immunotherapy has the potential to mount an ongoing, dynamic immune response that can kill tumor cells for an extended time after the conventional therapy has been administered. Such a long-lasting response is potentially able to completely eradicate tumor cells, rather than producing only a temporary killing of cells. The most promising immune-based treatments are monoclonal antibodies that act as checkpoint inhibitors (e.g. ipilimumab and nivolumab), adoptive cell therapy (e.g. T-cells expressing chimeric antigen receptors) and vaccines (e.g. sipuleucel-T). Ipilimumab is currently approved for the treatment of metastatic melanoma and sipuleucel-T is approved for advanced prostate cancer. There is great interest in immunotherapy in other solid tumors, potentially used alone or in a multimodal fashion with chemotherapy and/or biological drugs. In this paper, we review recent advances in immuno-oncology in solid malignancies (except melanoma) as were discussed at the inaugural meeting of the Campania Society of Oncology Immunotherapy (SCITO).

CT-guided radiofrequency ablation in the treatment of recurrent rectal cancer.

OBJECTIVE: Locally recurrent rectal adenocarcinoma remains a therapeutic challenge that is unsatisfactorily managed by surgery and radiation therapy or chemotherapy. Palliative CT-guided radiofrequency ablation was used in 14 patients with recurrent rectal adenocarcinoma who had been previously treated with abdominoperineal resection and radiation therapy. Follow-up CT or MRI was performed at 3, 6, 12, and 24 months. Pain palliation was monitored by the brief pain inventory (BPI). CONCLUSION: One month after radiofrequency ablation, 11 patients reported satisfactory BPI mean scores reduction compared to baseline (from 7.6 to 3.4 and from 5.1 to 1.6 for worst and average pain, respectively). In two unresponsive patients, retreatment was successfully performed at 3 months. After 24 months, worst and average pain scores further decreased (to 2.6 and 0.8, respectively) in 10 patients, who, at imaging, showed an ablation zone covering the entire original lesion in two patients and incomplete ablation in eight. In our experience, radiofrequency ablation is a safe and effective palliative treatment for patients with recurrent rectal adenocarcinoma.

Oxycodone controlled-release as first-choice therapy for moderate-to-severe cancer pain in Italian patients: results of an open-label, multicentre, observational study.

BACKGROUND AND OBJECTIVES: Cancer pain affects patients at all stages of the disease and there are clear guidelines for its management. Morphine is considered the first-choice strong opioid in the treatment of moderate-to-severe pain; however, numerous studies have shown that oxycodone controlled-release (CR) has a similar efficacy and safety profile. The purpose of this study was to evaluate the efficacy and tolerability of oxycodone CR as a first-line strong opioid for the treatment of moderate-to-severe pain in Italian cancer patients. METHODS: This was a prospective, open-label, multicentre, observational trial carried out at 15 locations across Italy. Patients with a referral for cancer-related pain of > or =5 on a 10-point numerical rating scale were enrolled. Patients were treated with oral oxycodone CR and monitored for 21 days. Dosage was individualized for each patient and up-titrated until effective pain control was achieved. Pain, adverse events and quality-of-life scores were assessed throughout the study. RESULTS: 390 patients (174 females and 216 males) with a mean age of 66 +/- 11 years were evaluated. The average daily dose ranged from 22.84 on day 1 to 40 mg/day on day 21. Pain intensity (assessed on a 10-point numerical rating scale) decreased significantly within 1 day of treatment commencement (p = 0.00001) and continued to decrease throughout the study period (from a mean 7.22 at baseline to a mean 2.11 points on day 21). Adverse events were mild to moderate in intensity and consisted of common opioid-related events. Ten patients (2.6%) discontinued the study because of adverse events and four (1%) because of uncontrolled pain. All aspects of activities of daily life assessed were improved by study end. CONCLUSIONS: Oxycodone CR is efficacious and well tolerated as a first-line strong opioid for the treatment of moderate-to-severe cancer-related pain in Italian patients.

Chemotherapy-induced neutropenia and treatment efficacy in advanced non-small-cell lung cancer: a pooled analysis of three randomised trials.

BACKGROUND: Chemotherapy is the standard treatment for advanced non-small-cell lung cancer, and myelosuppression is a common side-effect. We aimed to assess whether haematological toxic effects could be a biological measure of drug activity and a marker of efficacy. METHODS: We analysed data for 1265 patients who received chemotherapy (vinorelbine, gemcitabine, gemcitabine and vinorelbine, cisplatin and vinorelbine, or cisplatin and gemcitabine) within three randomised trials. Primary landmark analyses were restricted to 436 patients who received all six planned chemotherapy cycles and who were alive 180 days after randomisation. Neutropenia was categorised on the basis of worst WHO grade during chemotherapy: absent (grade 0), mild (grade 1-2), or severe (grade 3-4). All statistical analyses were stratified by treatment allocation. Analyses were repeated in the out-of-landmark group (829 patients), stratifying by treatment allocation and number of chemotherapy cycles. The primary endpoint was overall survival. FINDINGS: In the landmark group, hazard ratios of death were 0.65 (0.46-0.93) for patients with severe neutropenia and 0.74 (0.56-0.98) for those with mild neutropenia. Median survival after the landmark time of 180 days was 31.4 weeks (95% CI 25.7-39.6) for patients without neutropenia compared with 42.0 weeks (32.7-59.7) for patients with severe neutropenia, and with 43.7 weeks (36.6-66.0) for those with mild neutropenia (severe vs mild vs no neutropenia p=0.0118). Findings were much the same for the out-of-landmark group. INTERPRETATION: Neutropenia during chemotherapy is associated with increased survival of patients with advanced non-small-cell lung cancer, and its absence might be a result of underdosing. Prospective trials are needed to assess whether drug dosing guided by the occurrence of toxic effects could improve efficacy of standard regimens.

Carboplatin plus vinorelbine plus G-CSF in elderly patients with extensive-stage small-cell lung cancer: a poorly tolerated regimen. Results of a multicentre phase II study.

PURPOSE AND METHODS: A multicentre phase II trial (single-stage design) was undertaken to test the activity and toxicity of carboplatin (AUC 5 according to Calvert, day 1) plus vinorelbine (25 mg/m(2) days 1 and 8) with lenograstim support, every 3 weeks in the first line treatment of elderly patients, aged 65 or more, affected by extensive small-cell lung cancer (SCLC). The primary end-point of the trial was the objective response rate. Twenty-three responses among 37 patients were considered necessary to proceed to a phase III trial. RESULTS: Twenty-eight patients were enrolled (median age 70 years). Treatment was remarkably toxic. Three patients died while on treatment. Eleven patients (39.3%, 95% exact confidence interval (CI): 21.5-59.4) had an objective response, that was complete in 2 cases. Median time to progression was 5.1 months (95% CI: 3.3-6.7). Median survival was 7.9 months (95% CI: 4.8-14.4). CONCLUSION: Carboplatin plus vinorelbine is poorly tolerated and not sufficiently active to warrant phase III comparison with standard chemotherapy regimens in elderly patients with extensive SCLC.