- Results of long-term survival analysis of the phase III EMPOWER-Cervical 1 multicenter clinical trial show that immune checkpoint inhibitor cemiplimab monotherapy continues to show superior efficacy over chemotherapy.
- Data evidence that cemiplimab increases overall survival versus chemotherapy with a 35% lower risk of death in patients with recurrent or metastatic cervical cancer and disease progression on first-line chemotherapy.
- The CheckMate 358 multicenter phase I/II clinical trial is the first to assess immune-based regimens without chemotherapy in the first-line setting in recurrent or metastatic cervical cancer.
- Safety and efficacy data from this study show that chemotherapy-free dual immunotherapy with nivolumab and ipilimumab can provide durable tumor regression with significant yet manageable toxicity, irrespective of PD-L1 status.
- Results of both these studies have now been presented on the ground at the annual ESMO Congress 2022 by lead investigator Ana Oaknin, Principal Investigator of VHIO’s Gynecological Malignancies Group and Head of the Gynecologic Tumors Unit at the Vall d’Hebron University Hospital, Vall d’Hebron Barcelona Hospital Campus.
Cervical cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women globally. The GLOBOCAN 2020 report on cancer incidence and mortality (1), produced by the International Agency for Research on Cancer (IARC), estimates that there were 604,000 new cases of cervical cancer and 342,000 deaths from this disease worldwide in 2020.
Patients with cervical cancer who have been diagnosed early and received standard therapy, have an excellent prognosis with an overall survival rate of 90-95%. In patients with advanced disease, however, the prognosis is poor with a 5‑year survival rate of 15%.
For women suffering from recurrent and/or metastatic cervical cancer, whose disease has progressed on or after platinum-based chemotherapy, the few second line systemic therapies available fail to demonstrate any survival benefit. Improving outcomes for these patients therefore represents a critical, unmet clinical need.
Presented during this week’s annual Congress of the European Society for Medical Oncology (ESMO), 09 – 13 September, Paris, France, results of several studies across different tumor types are showing the increasing promise of immune-based therapy as monotherapy or in combination, as well as a potential alternative to chemotherapy.
Among these, data from two different studies directed by VHIO’s Ana Oaknin, EMPOWER-CERVICAL 1 (2) and CheckMate 358 (3) show how immune-based strategies are stepping up in the treatment of recurrent or metastatic cervical cancer. Presented by Ana Oaknin at same Mini Oral session at the ESMO Congress 2022, results of both studies point to the promise of immunotherapy in improving outcomes for some of these patients.
Ringing in the PD-1 blocking antibody cemiplimab as monotherapy in recurrent or metastatic cervical cancer
Patients with recurrent or metastatic cervical cancer with disease progression on or after first-line platinum-based chemotherapy have no other current, effective treatment options. Seeking out new therapeutic avenues therefore represents an unmet clinical need. Cemiplimab is a monoclonal antibody which binds to the programmed death-1 (PD-1) receptor thereby potentiating an immune response to tumor cells and is used to treat lung and skin cancers.
The randomized, multicenter international phase III EMPOWER-Cervical 1 – Gynecologic Oncology Group (GOG) & European Network for Gynaecological Oncological Trial groups (ENGOT) – study was designed to assess the efficacy of PD-1 inhibitor cemiplimab as monotherapy versus physician’s-choice chemotherapy in patients with recurrent or metastatic cervical cancer with squamous cell carcinoma or adenocarcinoma after progression on first-line chemotherapy, measured by overall survival as the primary endpoint.
Building on previous data from this study that published earlier this year in The New England Journal of Medicine (4), final overall survival results show that this immune-based contender continues to show superior efficacy over chemotherapy in this patient population.
“Data from long-term follow-up show that cemiplimab can reduce the risk of death by up to 35% in this patient population. Our findings further support cemiplimab immunotherapy as a new and much needed treatment option for some of these patients. Considering that women suffering from cervical cancer are most frequently diagnosed between the ages of 35 and 44 years, we must collectively strive to extend the survival of these younger patients,” says Ana Oaknin, lead investigator and senior author of this present study.
EMPOWER-Cervical 1 enrolled 608 patients who were randomized by histology: squamous cell carcinoma or adenocarcinoma, including adenosquamous carcinoma, and were divided into two groups. The first group received treatment with cemiplimab and the second, physician’s choice single-agent chemotherapy. Median duration of follow-up was 30.2 months, providing very significant overall survival data.
Cemiplimab improved overall survival, lowering the risk of death by up to 35%. In patients with squamous cell carcinomas this reduction was 31% and in patients with adenocarcinomas cemiplimab a 45% lower risk of death was achieved.
“Importantly, superior overall survival compared with chemotherapy was achieved independently of PD-L1 expression status, supporting a change in clinical practice for this patient population,” concludes Ana Oaknin.
CheckMate 358: putting immunotherapy to the test in first-line without chemotherapy
Encouraged by the clinical activity achieved by immune-based strategies in patients with recurrent or metastatic cervical cancer with disease progression after first-line treatment with chemotherapy, the CheckMate 358 investigators led by VHIO’s Ana Oaknin sought to assess the efficacy of chemotherapy-free immunotherapy with PD-1 inhibitor nivolumab and anti-CTLA-4 monoclonal antibody ipilimumab in the first-line setting.
“Anti-PD-1-based treatment has been approved in the first-and second-line settings for patients expressing PD-L1, however objective response rates in studies assessing the use of single agent immunotherapy have not exceeded 15%,” observes Ana Oaknin, first author and Principal Investigator of this phase I/II clinical trial.
CheckMate 358 is the first study to assess immune-based regimens as first-line treatment without chemotherapy. Up until now, other studies have assessed immunotherapy in combination with chemotherapy in this setting. This present multicenter international clinical trial enrolled 176 patients who were divided into three cohorts; one group of patients were treated with nivolumab monotherapy, and the other two groups received regimens of nivolumab plus ipilimumab.
“Our safety and efficacy data show that this novel strategy can achieve durable tumor regression with significant but manageable toxicity, regardless of PD-L1 status, and therefore warrants further investigation,” concludes Oaknin.
References:
1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249.
2. 519MO – Phase III EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 trial of cemiplimab in recurrent or metastatic (R/M) cervical cancer: Long-term survival analysis. Oaknin, B.J. Monk, L. Polastro, A. Cristina de Melo, H.S. Kim, Y.M. Kim, A.S. Lisyanskaya, V. Samouëlian, D. Lorusso, F.B. Damian, C.-L. Chang, S. Takahashi, D. Ramone, B. Maćkowiak-Matejczyk, J. Li, S. Jamil, M.D. Mathias, M.G. Fury, K.S. Tewari.
ESMO Congress 2022 session details:
Mini Oral session 1: Gynaecological cancers
Date: Saturday 10th September
Session time: 08:30 – 10:00
Speaker: Ana Oaknin
Lecture Time: 08:30 – 08:35h
3. 520MO – Safety and efficacy of nivolumab (NIVO) ± ipilimumab (IPI) in patients (pts) with recurrent/metastatic cervical cancer (R/M Cx Ca) in Checkmate 358. A.Oaknin, K.N. Moore, T. Meyer, J.L. González, L. Devriese, A. Amin, C.D. Lao, V. Boni, W.H. Sharfman, J.C. Park, M. Tahara, S.L. Topalian, M.E. Magallanes Maciel, A. Molina Alavez, A. Khan, C. Copigneaux, M. Lee, C. Garnett-Benson, X. Wang, R.W. Naumann.
ESMO Congress 2022 session details:
Mini Oral session 1: Gynaecological cancers
Date: Saturday 10th September
Session time: 08:30 – 10:00h
Speaker: Ana Oaknin
Lecture Time: 08:40 – 08:45h
4. Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouëlian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Maćkowiak-Matejczyk B, Guerra Alía EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555.
