Randomized, phase III trial of figitumumab in combination with erlotinib versus erlotinib alone in patients with nonadenocarcinoma nonsmall-cell lung cancer

Scagliotti, Giorgio Vittorio; Bondarenko, Igor; Blackhall, Fiona; Barlési, Fabrice; Hsia, Te‐Chun; Jassem, Jacek; Milanowski, Janusz; Popat, Sanjay; Sánchez-Torres, J.M.; Novello, Silvia; Benner, R. J.; Green, S.; Molpus, Kathleen; Soria, Jean Charles; Shepherd, Frances A.

doi:10.1093/annonc/mdu517

Cited by 53 publications

(41 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There were six types of cancer included: breast cancer, colorectal cancer, pancreatic cancer, lung cancer, prostate cancer, and ovarian cancer. More details about these cancers are: advanced hormone-receptor-positive breast cancer [14] (NCT00372996, 2015), metastatic colorectal cancer [15], wild-type KRAS metastatic colorectal cancer [21], mutant KRAS metastatic colorectal cancer [22], metastatic pancreatic cancer [12, 20], metastatic adenocarcinoma of the pancreas [23], and advanced-stage non-small-cell lung cancer [16, 17, 19, 24, 25] (NCT00887159, 2015). Study phase information: 2 phase-Ib/II studies, 1 phase-I/II study, 7 phase-II studies, 3 phase-III studies, 1 phase-II/III study, and 3 unknown phase studies.…”

Section: Resultsmentioning

confidence: 99%

“…Some studies [13–15] revealed IGF-1R inhibitors could shorten OS and PFS. However, more studies [16–25] showed IGF-1R mono-antibodies had no significant value in cancer treatment. Three data from ongoing clinical trials (NCT00372996, 2015; NCT00887159, 2015; NCT00684983, 2016) also indicated insignificant cancer curative value of anti-IGF-1R agents.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Update of IGF-1 receptor inhibitor (ganitumab, dalotuzumab, cixutumumab, teprotumumab and figitumumab) effects on cancer therapy

Wang

et al. 2017

Oncotarget

View full text Add to dashboard Cite

BackgroundPrognostic studies of insulin-like growth factor-1 receptor(IGF-1R) inhibitors in cancer therapy had promising results in infratests, which exhibited that IGF-1R signalling was crucial in cancer cells growth. However, the conclusion of later clinical trials revealed a dim future for IGF-1R inhibitors to treat cancer. We conducted this analysis to figure out how IGF-1R inhibitors acted in clinical cancer therapy.Material and MethodsWe searched up-to-date studies about the single agent of IGF-1R inhibitors or combination with other therapies in solid tumor. Five IGF-1R anti-agents were involved. The primary endpoint was progression-free survival (PFS). The secondary endpoint was overall survival (OS).Result17studies were enrolled. The results was not significant in overall survival (I2=37.1%, P=0.080, HR=1.08, 95% CI=0.97-1.21) and in progression-free survival (I2=0.0%, P=0.637, HR=1.05, 95% CI=0.98-1.12). OS for dalotuzumab, breast cancer, colorectal cancer, and PFS for prostate cancer even indicated harmful effects.ConclusionSo far, anti-IGF-1R mono-antibodies did not make significant differences in solid tumor prognosis. On the contrary, pessimistic effects were shown in the dalotuzumab, breast cancer, colorectal cancer and prostate cancer subgroups. Further studies of IGF-1R anti-agents were needed, but unwarranted in unselected patients by predictive biomarkers.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Update of IGF-1 receptor inhibitor (ganitumab, dalotuzumab, cixutumumab, teprotumumab and figitumumab) effects on cancer therapy

Wang

et al. 2017

Oncotarget

View full text Add to dashboard Cite

show abstract

“…However, more recent studies have suggested that, in EGFR wild-type populations, erlotinib may be inferior to single-agent cytotoxic agents, such as docetaxel. 7 To improve clinical outcomes, EGFR inhibitors have been combined with numerous other therapies, including vascular endothelial growth factor (VEGF)-targeting agents, 8 Src inhibitors, 9 insulin-like growth factor (IGF) inhibitors, 10 and cyclooxygenase-2 (COX-2) inhibitors. 11 …”

Section: Introductionmentioning

confidence: 99%

Phase 1 study of romidepsin plus erlotinib in advanced non-small cell lung cancer

et al. 2015

View full text Add to dashboard Cite

Purpose Preclinical studies demonstrated anti-tumor efficacy of the combination of the histone deacetylase (HDAC) inhibitor romidepsin plus erlotinib in non-small cell lung cancer (NSCLC) models that were insensitive to erlotinib monotherapy. We therefore, studied this combination in a phase 1 clinical trial in previously treated advanced NSCLC. Methods Romidepsin (8 or 10 mg/m2) was administered intravenously on days 1, 8, and 15 every 28 days in combination with erlotinib (150 mg orally daily), with romidepsin monotherapy lead-in during Cycle 1. Correlative studies included peripheral blood mononuclear cell HDAC activity and histone acetylation status, and EGFR pathway activation status in skin biopsies. Results A total of 17 patients were enrolled. Median number of prior lines of therapy was 3 (range 1–5). No cases had a sensitizing EGFR mutation. The most common related adverse events were nausea, vomiting, and fatigue (each 82%), diarrhea (65%), anorexia (53%), and rash (41%). Dose-limiting nausea and vomiting occurred at the romidepsin 10 mg/m2 level despite aggressive antiemetic prophylaxis and treatment. Among 10 evaluable patients, the best response was stable disease (n = 7) and progressive disease (n = 3). Median progression-free survival (PFS) was 3.3 months (range 1.4–16.5 months). Prolonged PFS (>6 months) was noted in a KRAS mutant adenocarcinoma and a squamous cell cancer previously progressed on erlotinib monotherapy. Romidepsin monotherapy inhibited HDAC activity, increased histone acetylation status, and inhibited EGFR phosphorylation. Conclusions Romidepsin 8 mg/m2 plus erlotinib appears well tolerated, has evidence of disease control, and exhibits effects on relevant molecular targets in an unselected advanced NSCLC population.

show abstract

“…The rational combination of cetuximab and afatinib appear to combine with favorable response rates, albeit with higher toxicity (23). The insulin growth factor-1 receptor monoclonal antibody figitumumab (Pfizer) did not demonstrate a survival benefit and also had significantly higher toxicities when combined with erlotinib (122). …”

Section: Combination Treatment Strategies and Precision Medicinementioning

confidence: 99%

Imprecision in the Era of Precision Medicine in Non-Small Cell Lung Cancer

et al. 2017

View full text Add to dashboard Cite

Over the past decade, major advances have been made in the management of advanced non-small cell lung cancer (NSCLC). There has been a particular focus on the identification and targeting of putative driver aberrations, which has propelled NSCLC to the forefront of precision medicine. Several novel molecularly targeted agents have now achieved regulatory approval, while many others are currently in late-phase clinical trial testing. These antitumor therapies have significantly impacted the clinical outcomes of advanced NSCLC and provided patients with much hope for the future. Despite this, multiple deficiencies still exist in our knowledge of this complex disease, and further research is urgently required to overcome these critical issues. This review traces the path undertaken by the different therapeutics assessed in NSCLC and the impact of precision medicine in this disease. We also discuss the areas of “imprecision” that still exist in NSCLC and the modern hypothesis-testing studies being conducted to address these key challenges.

show abstract

Randomized, phase III trial of figitumumab in combination with erlotinib versus erlotinib alone in patients with nonadenocarcinoma nonsmall-cell lung cancer

Abstract: NCT00673049.

Cited by 53 publications

References 17 publications

Update of IGF-1 receptor inhibitor (ganitumab, dalotuzumab, cixutumumab, teprotumumab and figitumumab) effects on cancer therapy

Update of IGF-1 receptor inhibitor (ganitumab, dalotuzumab, cixutumumab, teprotumumab and figitumumab) effects on cancer therapy

Phase 1 study of romidepsin plus erlotinib in advanced non-small cell lung cancer

Imprecision in the Era of Precision Medicine in Non-Small Cell Lung Cancer

Contact Info

Product

Resources

About