Bevacizumab Plus Chemotherapy for Metastatic Cervical Cancer: a step forward

  • Date: 29 Aug 2014
  • Author: Ramon Andrade de Mello, Pedro Madureira
  • Affiliation: Ramon Andrade de Mello: Department of Biomedical Sciences and Medicine, University of Algarve, Faro / Department of Medical Oncology, Portuguese Oncology Institute, Porto, Portugal. Pedro Madureira: Instituto de Ciências Biomédicas Abel Salazar (ICBAS), University of Porto / Instituto de Biologia Molecular e Celular (IBMC), Porto, Portugal
  • Link: Read the original article
  • Topic: Gynaecologic malignancies
Ramon Andrade-de-Mello
Pedro Madureira

Cervical cancer is a highly prevalent disease worldwide, mainly in countries where screening strategies are not well implemented (1). Despite the prophylactic measures currently available, cancer of the cervix is the second most common cancer among women, and in the metastatic/advanced/recurrent setting, the overall survival (OS) remains very poor.

Until recently, standard doublet regimen chemotherapy was the treatment of choice. Since 1985, cisplatin has an important role in the treatment of metastatic/advanced/recurrent cervical cancer (2-5).

In 2014, Tewari et al published an interesting study (6) that evaluated 452 patients who were randomly assigned to chemotherapy (cisplatin 50 mg/m2 plus paclitaxel 135 or 175 mg/m2 day 1 or topotecan 0.75 mg/m2 day 1 to 3 plus paclitaxel 175 mg/m2 day 1, every 3 weeks until disease progression, complete response or unacceptable toxic effects) with or without bevacizumab 15 mg/Kg. The primary end-point was OS.

At a median follow-up of 20.8 months, response rate (48% versus 36%, p = 0.008), PFS (8.2 versus 5.9 months, p = 0.002), OS (17 versus 13.3 months, p = 0.004) were superior in the bevacizumab-chemotherapy group compared to the chemotherapy-alone group.

Despite the increased toxicity profile in the bevacizumab group, hypertension of grade 2 or higher (25% vs. 2%, P<0.001), gastrointestinal bleeding  of grade 3 or higher (2% vs. <1%, P = 0.37), gastrointestinal/genitourinary fistulas of grade 3 or higher (6% vs. 0%, P = 0.002), thromboembolic events of grade 3 or higher (8% vs. 1%, P = 0.001), the addition of bevacizumab to the standard chemotherapy was not associated with a decrease in quality of life.

Based on this study, the addition of bevacizumab to platinum-paclitaxel should be considered a new standard of care in this setting. However, it is very important that oncologists are aware of the toxicity profile and patient tolerance to this regimen in order to optimize the clinical outcomes. Currently, the discovery of novel biomarkers and the implementation of targeted agents/chemotherapy combinations are of interest in this field in order to ensure an improvement in patient outcomes with acceptable tolerability.

Discussion questions

  1. What are the possible predictive biomarkers to anti-angiogenesis targeted therapies in advanced cervical cancer patients?
  2. Could it be useful to use VEGF SNPs as biomarkers for the treatment tailoring in this setting?
  3. What are the potential targeted agents that could emerge for the advanced cervical cancer treatment setting? Pazopanib? Sorafenib? mTOR inhibitors? cetuximab?
  4. Should the maintenance treatment with bevacizumab be studied in those patients with advanced cervical cancer, who are responders to bevacizumab-chemotherapy regimens?

References

  1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9-29.
  2. Bonomi P, Blessing JA, Stehman FB, DiSaia PJ, Walton L, Major F. Randomized trial of three cisplatin dose schedules in squamous-cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol. 1985;3(8):1079-85.
  3. Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, et al. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2004;22(15):3113-9.
  4. Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, et al. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009;27(28):4649-55.
  5. Long HJ, Bundy BN, Grendys EC, Benda JA, McMeekin DS, Sorosky J, et al. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol. 2005;23(21):4626-33.
  6. Tewari KS, Sill MW, Long HJr, Penson RT, Huang H, Ramondetta LM, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014;370(8):734-43.