Combination atezolizumab, bevacizumab, pemetrexed and carboplatin for metastatic EGFR mutated NSCLC after TKI failure.

INTRODUCTION: Acquired resistance to TKI is an important unmet need in the management of EGFR mutated lung cancer. Recent clinical trial IMPower150 suggested that combination approach with VEGF inhibitor, check point inhibitor immunotherapy and platinum-based chemotherapy was effective in oncogene driven lung cancer. The current trial examined the efficacy of a modified regimen in an EGFR mutated cohort. METHODS: An open-labelled, single arm, phase II study was conducted in patients with EGFR mutated NSCLC who had progressed on at least one EGFR TKI. For those with T790M mutation, radiological progression on osimertinib was required for enrolment. Patients were treated with combination atezolizumab (1200 mg), bevacizumab (7.5 mg/kg), pemetrexed (500 mg/m2) and carboplatin (AUC 5) given once every 3 weeks until progression. RESULTS: Forty patients were enrolled. Median age was 62 (range 45-76) years. More than one half (23/40, 57.5%) had progressed on osimertinib. PD-L1 expression was < 1% in 52.5%. Median follow-up time was 17.8 months. ORR was 62.5%. Median PFS was 9.4 months (95% CI: 7.6 - 12.1). One year OS was 72.5% (95% CI: 0.56-0.83). Treatment related grade 3 or above adverse events (AE) occurred in 37.5% (15/40). Immune-related AE occurred in 32.5% (13/40) patients. Quality of life measures of function and symptoms did not change significantly throughout the course of treatments. Post-trial rechallenge with EGFR TKI containing regimen resulted in PFS of 5.8 months (95% CI 3.9-10.0 months). CONCLUSION: Combination approach of atezolizumab, bevacizumab, pemetrexed and carboplatin achieved promising efficacy in metastatic EGFR mutated NSCLC after TKI failure. The results were comparable with taxane based regimen of IMPower150 while toxicity profile was improved.

Can Quantitative Measures of T790M Allelic Fraction Predict Survival Outcomes in Patients Receiving Osimertinib? Observations From an Early Access Programme.

AIMS: Multiple studies have shown conflicting results on the correlation between the EGFR T790M quantitative level and survival outcomes in osimertinib-treated patients. We sought to validate such correlations using data from an osimertinib early access programme (EAP) providing access for metastatic non-small cell lung cancer patients with limited treatment options. PATIENTS AND METHODS: This observational, multicentre, retrospective analysis included EAP participants who received osimertinib until disease progression, intolerable toxicities or death. Digital droplet polymerase chain reaction-based quantitative plasma genotyping was carried out upon disease progression and data were analysed to explore the relationships between T790M mutant allele fraction (MAF), T790M copy number, MAF ratio and post-osimertinib overall survival. Real-world treatment outcomes and safety were also evaluated. RESULTS: Data from 156 EAP participants were analysed (median follow-up 37.7 months). The median age was 62 years, 62.2% were women, 79.5% were never-smokers, 60.9% had Eastern Cooperative Oncology Group performance status 0/1. In patients with available plasma data (n = 114), T790M MAF (%) showed no significant relationships with overall survival (hazard ratio 1.02; 95% confidence interval 0.99-1.04) or time to treatment discontinuation (TTD) (hazard ratio 1.01; 95% confidence interval 0.98-1.04). Absolute T790M copy number and T790M to activating EGFR mutation MAF ratio also showed no prognostic value. The investigator-assessed response rate was 42.3% and the disease control rate was 85.5%. The median TTD was 15.8 (95% confidence interval 12.5-18.5) months and the median overall survival was 22.3 (95% confidence interval 18.6-26.1) months. CONCLUSION: T790M MAF did not correlate with TTD or overall survival in this EAP cohort but limitations should not be overlooked. Observed survival outcomes and the toxicity profile were consistent with data from other real-world series.

Percutaneous cementoplasty of osteolytic metastases induces immediate and long-lasting pain relief in oncological patients.

OBJECTIVE: To evaluate the clinical efficacy of percutaneous cementoplasty with respect to pain relief in patients with refractory painful bone metastases. DESIGN: Case series. SETTING: Regional hospital, Hong Kong. PATIENTS: All oncological patients with painful bone metastases despite conventional treatment seen between October 2006 and May 2010 were recruited. INTERVENTIONS: Cementoplasty with or without radiofrequency ablation. MAIN OUTCOME MEASURES: Pain score before and after the procedure. RESULTS: In all, 12 patients with 13 lesions received cementoplasty. Two patients were excluded from the analysis because of inadequate documentation of pain score due to rapid disease progression. For the remaining 10 patients with 11 metastases, the primary sites were the lung (n=3), renal cell carcinoma (n=2), rectum (n=2), pancreas (n=1), multiple myeloma (n=1), and soft tissue sarcoma (n=1). The locations of the metastatic lesions were scapula (n=1), thoracic vertebrae (n=1), lumbar vertebrae (n=3), and pelvic bones (n=6). Eight lesions were treated by cementoplasty alone, whereas the other three associated with large soft tissue components had radiofrequency ablation followed by cementoplasty in a single setting. Immediate or near-immediate pain relief after treatment was achieved in 10 out of 11 lesions; the median pain score was 5 before treatment and decreased to 2 a week after treatment (P=0.039). In all lesions for which the pain was successfully controlled in the first week, the palliation effect persisted at subsequent follow-ups. The median follow-up period for these patients was 16 weeks, and the longest pain-relieving effect was at least 9 months. CONCLUSION: In our experience, cementoplasty with or without radiofrequency ablation achieves satisfactory and long-lasting pain control in oncological patients with bone metastases. This is the first local study to describe the effect of cementoplasty for pain relief. Patients with painful bone metastases that are refractory to conventional treatments can benefit from cementoplasty, which should therefore be considered when conservative treatments fail.