Chemotherapy with cetuximab versus chemotherapy alone for chemotherapy-naive advanced non-small cell lung cancer

Lin

et al. 2017

Intl Journal of Cancer

Agents targeting epidermal growth factor receptor (EGFR) are used to treat head and neck squamous cell carcinoma (HNSCC); however, their efficacy and safety is poorly understood. Here we evaluated the efficacy and safety of anti-EGFR agents administered concurrently with standard therapies for HNSCC. Randomized controlled trials that evaluated addition of EGFR targeted therapy versus standard therapy alone were included. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), overall response rate (ORR), locoregional control, and severe adverse events (SAEs, grade ≥ 3). Sixteen eligible trials with 4031 patients were included. Addition of anti-EGFR regimens to standard therapy significantly improved OS of patients with HNSCC (HR = 0.89; 95% CI, 0.82-0.96), with a moderately elevated rate of SAEs (RR = 1.08; 95% CI, 1.03-1.13). Subgroup analysis indicated that the survival benefit was observed when cetuximab was administered concurrently with radiotherapy (RT) for stage III/IV patients (HR = 0.76; 95% CI, 0.61-0.94; p = 0.01), or with chemotherapy for recurrent or metastatic (R/M) HNSCC (HR = 0.86; 95% CI, 0.78-0.95; p = 0.005). Significantly increased ORR (RR = 1.51; 95% CI 1.05-2.18) and PFS (HR = 0.72; 95% CI, 0.59-0.88) were found in R/M HNSCC patients treated with anti-EGFR plus chemotherapy, while no significant improvements were found in stage III/IV patients treated with anti-EGFR plus standard therapy. In conclusion, addition of cetuximab to standard therapy may improve outcomes for R/M HNSCC patients, while causing a moderate increase in SAEs. For stage III/IV patients, anti-EGFR mAb plus RT can improve OS compared with RT alone, while replacement of chemotherapy with EGFR mAb or adding EGFR mAb to combined chemotherapy and RT did not improve outcomes.

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of anti‐EGFR agents administered concurrently with standard therapies for patients with head and neck squamous cell carcinoma: a systematic review and meta‐analysis of randomized controlled trials

Lin

et al. 2017

Intl Journal of Cancer

Expert Opinion on Biological Therapy

“…PFS, the primary endpoint, did not differ (4.4 vs 4.24 months, HR=0.902, 95% CI 0.761-1.069, p=0.24); OS showed a trend favouring the cetuximab arm but the trial was not powerful enough to demonstrate such small OS improvement (9.7 vs 8.4 months, HR=0.890 95% CI 0.754-1.051; p=0.17). Metanalyses pooling data from all four randomized trials described above (LUCAS, BMS100, BMS099 and FLEX) confirmed the modest but statistically significant advantage in OS of adding cetuximab to chemotherapy (53)(54)(55). Randomized studies are summarized in table 2.…”

Section: Phase III Studiesmentioning

confidence: 78%

Cetuximab for treating non-small cell lung cancer

Mazzarella

Guida

Curigliano

2018

Epidermal Growth Factor Receptor (EGFR)-dependent signaling plays a crucial role in epithelial cancer biology, and dictated the development of several targeting agents. The mouse-human chimeric antibody Cetuximab was among the first to be developed. After about two decades of clinical research it has gained a significant place in the management of advanced colorectal and head and neck cancers, whereas its development in non small cell lung cancer (NSCLC) has not led to a place in routine clinical practice, because of marginal clinical benefit despite statistically significant Phase III trials. Recent data from ongoing trials suggest that more careful selection based on molecular markers may identify good responders. Areas covered: In this article, the authors review the literature concerning basic science studies identifying EGFR as a therapeutic target, pharmacological development of Cetuximab, its pharmacodynamics and pharmacokinetics, and clinical trials on Cetuximab in NSCLC, focusing on recent findings on putative predictive biomarkers. Expert opinion: Cetuximab currently has no role in NSCLC treatment outside of research settings. We argue that failure to identify a predictive biomarker early on has hampered its chances to enter routine practice. Although recent research suggests benefit in highly selected patient subsets, its potential impact is severely dampened by lack of regulatory body approval and the emergence of competitors for the same niches.

“…Badania Son i współpracowników potwierdziły synergistyczne działanie cetuksymabu w skojarzeniu z cisplatyną także w liniach komórko-wych raka okrężnicy [48]. Udowodniono również skuteczność cetuksymabu w skojarzeniu z innymi chemioterapeutykami [49]. Badania kliniczne III fazy wskazują na możliwość zastosowania w niedrobnokomórkowym raku płuca także innych przeciwciał blokujących receptor EGF -matuzumab, panitumumab oraz necitumumab [4,46].…”

Section: Przeciwciała Stosowane W Innych Typach Nowotworów Złośliwychunclassified

Monoclonal antibodies in regulation of signal transduction of Epidermal Growth Factor Receptor (EGFR) pathway in cancer cells

Kampa¹,

Bednarek²,

Sypniewski³

2018

Ann. Acad. Med. Siles.

ST R ES ZCZ E NI EReceptor naskórkowego czynnika wzrostu EGFR (Epidermal Growth Factor Receptor), ze względu na jego ważny udział w patogenezie nowotworów złośliwych, jest obiektem intensywnych badań naukowych ostatnich lat. W wielu typach nowotworów wewnątrzkomórkowe szlaki sygnalizacyjne pobudzane przez EGFR mają wręcz kluczowe znaczenie w ich rozwoju. Z drugiej strony wykazano, iż EGFR może stanowić bardzo obiecujący punkt uchwytu dla czynników terapeutycznych. Podjęto próby modyfikacji transdukcji sygnału przekazywanego przez aktywny EGFR wewnątrz komórek poprzez blokowanie aktywności elementów tego szlaku bądź samego receptora. Wykazano też, że blokowanie receptora EGFR przez przeciwciała monoklonalne podwyższa efektywność stosowanych w terapii konwencjonalnych czynników przeciwnowotworowych, np. cisplatyny. Dodatkowo opracowano wiele terapii przeciwnowotworowych opierając się na zastosowaniu inhibitorów wybranych, kluczowych składowych szlaku sygnalizacyjnego EGFR, z których wiele bazuje na zastosowaniu przeciwciał monoklonalnych.kancerogeneza, terapia przeciwnowotworowa, transdukcja sygnału, EGFR, przeciwciała monoklonalne