Cilengitide

Cilengitide is an integrin inhibitor that, when added to cetuximab and platinum-based chemotherapy, has demonstrated potential clinical activity in patients with EGFR-expressing NSCLC.8

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For the multicenter, open-label, controlled phase 2 study, researchers enrolled 169 patients with advanced NSCLC and randomly assigned them 1:1 to receive cetuximab plus platinum-based chemotherapy alone or combined with cilengitide 2000 mg intravenously once weekly.

Results showed that median progression-free survival was 6.2 months in the cilengitide arm vs 5.0 months in the control arm (hazard ratio 0.72; P = .085). For patients with an EGFR histoscore of 200 or more, progression-free survival was 6.8 months and 5.6 months in the cilengitide and control arms, respectively (hazard ratio 0.57; P = .0446).

Researchers found that median overall survival was 13.6 months in the cilengitide arm and 9.7 months in the control arm (hazard ratio 0.81; P = .265), and in patients with an EGFR histoscore of 200 or more, median overall survival was 13.2 and 11.8 months, respectively (hazard ratio 0.95; P = .855). Further studies are warranted to evaluate cilengitide’s utility in advanced NSCLC.

“When we started to look at angiogenesis, there was some thought that maybe we had found the answer for treating all cancers but unfortunately it turned out like most other stories that it played a role but it was not going to be the final answer,” Dr Masters told Cancer Therapy Advisor. “This new small molecule anti-angiogenic drug could have a role in the treatment of NSCLC; it is an area we want to pursue because no one treatment will be right for every patient or for every cancer.”

BCD-021 (Bevacizumab Biosimilar)

BCD-021 is a compound being investigated as a biosimilar agent to bevacizumab. An international, phase 3 trial evaluating its equivalence to bevacizumab in 138 patients with advanced non-squamous NSCLC demonstrated non-inferiority in this setting.9

The study enrolled patients with stage IIIB/IV disease and randomly assigned them to receive BCD-021 or bevacizumab 15 mg/kg in combination with paclitaxel 175 mg/m2 and carboplatin AUC 6 every 3 weeks for up to 6 cycles until disease progression or until unacceptable toxicity. Results showed that overall response rate was about 42% with BCD-021 and approximately 39% with bevacizumab. There was no significant difference in complete response rate, partial response rate, stable disease, and progression rate between the 2 treatment arms. The adverse event profiles of BCD-021 and bevacizumab were deemed equivalent.

Checkpoint Inhibitors

“I don’t think we know the full story on nivolumab, pembrolizumab, or atezolizumab yet. Although those drugs are not brand new, we are still figuring out if they can be used in different settings,” Dr Masters concluded. “We will see studies coming out evaluating checkpoint inhibitors in the adjuvant setting, in combination with radiation therapy, and in earlier settings like as first-line therapy with chemotherapy.”

Reference

  1. Key statistics for lung cancer. American Cancer Society website. May 10, 2016. http://www.cancer.org/cancer/lungcancer-non-smallcell/detailedguide/non-small-cell-lung-cancer-key-statistics. Accessed May 10, 2016.
  2. Sequist LV, Goldman JW, Wakelee HA, Camidge R, Yu HA, Varga A, et al. Efficacy of rociletinib (CO-1686) in plasma-genotyped T790M-positive non-small cell lung cancer (NSCLC) patients (pts). J Clin Oncol. 2015;33(suppl; abstr 8001).
  3. Neal JW, Dahlberg SE, Wakelee HA, Aisner SC, Bowden M, Carbone DP, et al. Cabozantinib (C), erlotinib (E) or the combination (E+C) as second- or third-line therapy in patients with EGFR wild-type (wt) non-small cell lung cancer (NSCLC): A randomized phase 2 trial of the ECOG-ACRIN Cancer Research Group (E1512). J Clin Oncol. 2015;33(suppl; abstr 8003).
  4. ARIAD presents updated phase 1/2 clinical data on brigatinib in patients with alk+ non-small cell lung cancer [news release]. Cambridge, MA: ARIAD Pharmaceuticals; April 15, 2016. http://investor.ariad.com/phoenix.zhtml?c=118422&p=irol-newsArticle&ID=2157495. Accessed May 9, 2016.
  5. Gibbons DL, Chow LQ, Kim D, Kim S, Yeh T, Song X, et al. Efficacy, safety and tolerability of MEDI4736 (durvalumab [D]), a human IgG1 anti-programmed cell death-ligand-1 (PD-L1) antibody, combined with gefitinib (G): a phase I expansion in TKI-naïve patients (pts) with EGFR mutant NSCLC. Oral presentation at: European Lung Cancer Conference 2016; April 13-16, 2016; Geneva, Switzerland.
  6. Astrazeneca’s combination of durvalumab with tremelimumab shows clinical activity in non-small cell lung cancer irrespective of PD-L1 status [news release]. London, United Kingdom: AstraZeneca; February 8, 2016. http://www.businesswire.com/news/home/20160207005035/en/ASTRAZENECA%E2%80%99S-COMBINATION-DURVALUMAB-TREMELIMUMAB-SHOWS-CLINICAL-ACTIVITY. Accessed May 15, 2016.
  7. Shukuya T, Yamanaka T, Seto T, Daga H, Goto K, Saka H, et al. Nedaplatin plus docetaxel versus cisplatin plus docetaxel for advanced or relapsed squamous cell carcinoma of the lung (WJOG5208L): a randomised, open-label, phase 3 trial. Lancet Oncol. doi: 10.1016/S1470-2045(15)00305-8.
  8. Vansteenkiste J, Barlesi F, Waller CF, Bennouna J, Gridelli C, Goekkurt E, et al. Cilengitide combined with cetuximab and platinum-based chemotherapy as first-line treatment in advanced non-small cell lung cancer (NSCLC) patients: results of an open-label, randomized, controlled phase II study (CERTO) [published electronically ahead of print May 4, 2015]. Ann Oncol. doi: 10.1093/annonc/mdv219.
  9. Filon O, Orlov S, Burdaeva O, Kopp MV, Kotiv B, Alekseev, S, et al. Efficacy and safety of BCD-021, bevacizumab biosimilar candidate, compared to Avastin: Results of international multicenter randomized double blind phase III study in patients with advanced non-squamous NSCLC. J Clin Oncol. 2015;33(suppl; abstr 8057).

Topics:

Lung Cancer Non-Small Cell Lung Cancer