Comparative study analyzing survival and safety of bevacizumab/carboplatin/paclitaxel and cisplatin/pemetrexed in chemotherapy-naïve patients with advanced non-squamous bronchogenic carcinoma not harboring EGFR mutation

Abstract

PurposeThe majority of Egyptian patients with lung cancer present at a late stage of the disease. Bevacizumab/carboplatin/paclitaxel, as well as cisplatin plus pemetrexed, are both standard regimens for advanced non-squamous bronchogenic cancer. This study compares both regimens, in terms of efficacy and toxicity profile, in Egyptian patients.Patients and methodsThis is a randomized Phase II study comparing toxicity profile and survival in 41 chemotherapy-naïve patients with stage IIIB or IV non-squamous NSCLC, with an ECOG performance status of 0 to 2. The epidermal growth factor receptor (EGFR) mutation detection was performed prior to treatment of all patients. Patients in the first group received: bevacizumab 7.5 mg/m2 on Day 1 and Day 15; carboplatin area under the curve-5 on Day 1; and paclitaxel 60 mg/m2 on Day 1, Day 8, and Day 15 every 4 weeks. In the second group, patients received cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 every 3 weeks.ResultsThe combination of bevacizumab/carboplatin/paclitaxel demonstrated higher Grade III–IV toxicity than cisplatin/pemetrexed regarding sensory/motor neuropathy (P = 0.06), DVT (P = 0.23), proteinuria (P = 0.23), and hypertension (P = 0.11), as well as Grade II alopecia (P = 0.001); however, no significant difference in toxicities between both arms was recorded regarding nausea and vomiting (P = 0.66), hematological toxicity, febrile neutropenia (P = 1) and fatigue (P = 0.66). Progression-free survival was similar for both treatment arms with a median of 6 months (P = 0.978). Overall median survival was comparable in both arms, 16.07 months versus 16.01 months (P = 0.89).ConclusionBevacizumab/carboplatin/paclitaxel and cisplatin/pemetrexed provided meaningful and comparable efficacy in advanced non-squamous bronchogenic carcinoma not harboring EGFR mutation. No significant difference in toxicity was observed between both treatment arms, apart from bevacizumab/carboplatin/paclitaxel-related risks as DVT, hypertension, proteinuria, sensory/motor neuropathy, and alopecia.

The Role of EGFR Amplification in Deep Venous Thrombosis Occurrence in IDH Wild-Type Glioblastoma

“…As VEGF has been implicated in the same signaling cascades with TF as EGFR, we sought to determine whether bevacizumab therapy would influence our results. Bevacizumab adjuvant treatment in particular has been linked with increased thrombotic risk [33,61,62]. Multivariate analysis demonstrated there was not a statistically significant difference in our results when controlling for bevacizumab therapy (Table 3).…”

“…One study by Dou et al investigated EGFR mutation status and demonstrated an increased VTE risk in EGFR wild-type adenocarcinoma patients [66]. Other studies investigating anti-EGFR treatments have also noted an increased rate of thrombosis [33,61,62,[67][68][69][70]. The split consensus for the role of EGFR in NSCLC-associated VTE described above may explain why studies that focused on EGFR in other malignancies have not shown conclusive results.…”

Real‑world evidence of advanced non‑small cell lung carcinoma treated with an immune checkpoint inhibitor plus chemotherapy

“…For advanced NSCLC without driver gene alterations, such as those in EGFR, KRAS, ALK, ROS1 and BRAF, platinum-based doublet chemotherapy is considered to be the most common standard first-line treatment approach ( 4 ). In patients with advanced non-squamous carcinoma NSCLC, the treatment can be combined with bevacizumab and maintained with pemetrexed or bevacizumab following standard therapy ( 5 – 7 ). For patients with driver gene alterations, targeted therapy is often the first treatment approach, since the relevant agents can improve overall survival (OS) and the overall response rate (ORR).…”