During the upcoming annual meeting for the European Society for Medical Oncology (ESMO Congress 2023) held October 20 – 24, 2023 in Madrid, Spain, expect to see results from highly anticipated phase 3 clinical trials in gynecological cancers.

Among the new data to be presented, expect an entire spectrum presentations of how to  manage patients with cervical cancer. Late-breaking studies will be featured in Presidential and Proffered Paper Sessions, and the expectation is that the outcomes of the presented data could change the treatment landscape for women with these cancers.  Overall, these practice changing data demonstrates that novel therapies may delayed the time to relapse and, in some cases, lengthened survival.

“These are exciting results that address unmet needs in gynecological cancers,” said Professor Krishnansu S. Tewari, Director – Gynecologic Oncology Program, University of California, Irvine, USA.

Novel findings will be revealed across the range of gynecological cancers, including cervical, ovarian, and endometrial cancers. Cervical cancer usually presents as locally advanced disease in women who have not undergone screening. At this stage, the cancer is too large to remove surgically, and the standard treatment is chemotherapy with radiation. “Cervical cancer occurs in young women who are typically in the midst of their careers and have small children at home,” Tewari said.

“Standard treatment does lead to remission, but within two to three years the cancer can come back. Two trials that will be presented at the ESMO Congress 2023 will reveal new ways of treating locally advanced cervical cancer that significantly delay relapse, giving women who are in the prime of their lives more time free of cancer.”

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In one study, 68% of women who received the immunotherapy drug pembrolizumab on top of standard treatment were cancer-free at two years, compared to 57% of women allocated to placebo on top of standard treatment. [1]

A second study tested the impact of giving a combination of two different chemotherapy drugs ahead of standard treatment with chemotherapy plus radiation – a strategy called induction chemotherapy. [2] Women with locally advanced cervical cancer who received induction chemotherapy were 35% more likely to be cancer-free at five years and 39% more likely to be alive at five years compared to those who received standard treatment only.

“Induction chemotherapy could be an accessible treatment option because these drugs are available around the world, including in low-resource countries,” Tewari noted.

Also in cervical cancer, trials will be presented showing improvements in survival and delays in relapse with new treatments for women with cancer that has spread to other parts of the body or has come back after initially being treated with chemotherapy plus radiation.

Tisotumab vedotin
One trial tested a novel therapeutic approach with tisotumab vedotin (Tivdak®; Seagen and Genmab), a human monoclonal antibody directed against cell surface tissue factor (TF), which, via a protease-cleavable linker, covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE), to the antibody. [3] In 2021, the U.S. Food and Drug Administration granted accelerated approval for this antibody-drug conjugate (ADC) for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. The results of the trials presented at the ESMO 2023 Congress includes study outcomes from in women who had already received treatment for their metastatic or relapsed cervical cancer. [4] These results show that tisotumab vedotin lengthened survival, delayed relapse, and more often caused tumor shrinkage compared with chemotherapy.

Ovarian cancer
In ovarian cancer, achieving remission is a high unmet need, as approximately 85% of patients experience recurrent disease, with almost no long-term survival after recurrence. [5] At the ESMO Congress 2023, randomized trial data will be discussed showing that a novel targeted therapy, called senaparib (IMP4297) a novel poly(ADP-ribose) polymerase 1/2 inhibitor being developed by Junshi Biosciences and IMPACT Therapeutics, delayed the time to relapse in patients with newly diagnosed advanced disease. [6]

Endometrial cancer
Studies will also be presented in endometrial cancer, the most common gynecological cancer in the United States and Europe. [7][8] In Europe, more than 121,000 women were diagnosed with endometrial cancer in 2018 while in the US, it is estimated that over 66,000 women will be diagnosed in 2023. While there is no screening test, there is an early symptom — post-menopausal bleeding — which means that most endometrial cancers can be cured with a hysterectomy.

“Unfortunately, for the 15-20% of patients that have more aggressive disease, treatment options are very limited and that’s why the studies that will be presented at the ESMO Congress are remarkable. Two trials showed that adding immunotherapy to standard chemotherapy treatment significantly delayed relapse of the cancer in women with advanced/recurrent endometrial cancer compared to chemotherapy alone,” Tewari added [9][10]

Tewari also noted that the results that will be presented at the ESMO Congress 2023 have a very good chance of leading to regulatory approval of new treatments.

“These trials have set the stage for women with gynecological cancers to receive state-of-the-art therapies that delay the time to relapse, allowing women struggling with these cancers to live longer and live better,” he concluded.

Highlights of Prescribing Information
Tisotumab vedotin (Tivdak®; Seagen and Genmab) [Prescribing Information]

[1] Abstract – LBA38 ‘Pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer: A randomized, double-blind, phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study’ will be presented by Domenica Lorusso during Proffered Paper session 1 – Gynaecological cancers on Friday, 20 October 2023, 16:00 to 17:30 (CEST) in Sevilla Auditorium – Hall 9.
[2] Abstract – LBA8 ‘A randomised phase III trial of induction chemotherapy followed by chemoradiation compared with chemoradiation alone in locally advanced cervical cancer. The GCIG INTERLACE trial’ will be presented by Mary McCormack during Presidential 2 Session on Sunday, 22 October 2023, 16:30 to 18:15 (CEST) in Madrid Auditorium – Hall 6.
[3] Garcia. D Tisotumab Vedotin Significantly Prolongs Overall Survival in Patients with Recurrent/Metastatic Cervical Cancer Compared with Chemotherapy. ADC Review | Jouranal of Antibody-drug Conjugates [Article]
[4] Abstract – LBA9 ‘innovaTV 301/ENGOT-cx12/GOG-3057: A global, randomized, open-label, phase 3 study of tisotumab vedotin vs investigator’s choice of chemotherapy in 2L or 3L recurrent or metastatic cervical cancer’ will be presented by Ignace B. Vergote during Presidential 2 Session on Sunday, 22 October 2023, 16:30 to 18:15 (CEST) in Madrid Auditorium – Hall 6.
[5] Lorusso D, Mancini M, Di Rocco R, et al. The role of secondary surgery in recurrent ovarian cancer. Int J Surg Oncol. 2012;613980. doi: 10.1155/2012/613980.
[6] Abstract – LBA36 ‘Efficacy and safety of senaparib as maintenance treatment in patients with newly diagnosed advanced ovarian cancer (FLAMES Study): A randomized, double-blind, placebo-controlled, phase 3 trial’ will be presented by Xiaohua Wu during Proffered Paper session 1 – Gynaecological cancers on Friday, 20 October 2023, 16:00 to 17:30 (CEST) in Sevilla Auditorium – Hall 9.
[7] Schlumbrecht M, Wright K, George S. Unique considerations in early detection, risk, and awareness of endometrial cancer in Black women. Cancer Control. 2023;30:10732748231202952.
[8] Mahdi H, Ray-Coquard I, Lorusso D, et al. Evolving treatment paradigms in metastatic or recurrent low-grade endometrial cancer: When is hormonal-based therapy the preferred option? Int J Gynecol Cancer. 2023:ijgc-2023-004454. doi: 10.1136/ijgc-2023-004454.
[9] Abstract – LBA40 ‘Phase III double-blind randomized placebo controlled trial of atezolizumab in combination with carboplatin and paclitaxel in women with advanced/recurrent endometrial carcinoma’ will be presented by Nicoletta Colombo during Proffered Paper session 2 – Gynaecological cancers on Saturday, 21 October 2023, 08:45 to 10:00 (CEST) in Bilbao Auditorium – NCC.
[10] Abstract – LBA41 ‘Durvalumab (durva) plus carboplatin/paclitaxel (CP) followed by maintenance (mtx) durva ± olaparib (ola) as a first line (1L) treatment for newly diagnosed advanced or recurrent endometrial cancer (EC): results from the Phase III DUO-E/GOG-3041/ENGOT-EN10 trial’ will be presented by Shannon N. Westin during Proffered Paper session 2 – Gynaecological cancers on Saturday, 21 October 2023, 08:45 to 10:00 (CEST) in Bilbao Auditorium – NCC.

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