Expert Point of View: Ana Oaknin, MD, PhD

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The innovaTV 204 trial’s invited discussant, Ana Oaknin, MD, PhD, Head of the Gynecologic Cancer Program at Vall d’Hebron Institute of Oncology in Barcelona, was encouraged by the study’s findings.

“Of note, the response rate was 24%, the time to response was short, and the median duration of response was prolonged (possibly a consequence of the immune effect of tisotumab vedotin). The median progression-free survival and overall survival are compelling in this poor-prognosis population, so I agree with the investigators that the activity is clinically meaningful,” Dr. Oaknin commented.

Second-Line Therapies

“Platinum-based chemotherapy plus bevacizumab (GOG 204 protocol) is the standard first-line treatment for metastatic or recurrent cervical cancer, producing an overall survival of around 17 months. However, GOG 240 has created a new population: women who have experienced disease progression after bevacizumab. The question is which therapies we should study in the second-line setting,” Dr. Oaknin said.

Ana Oaknin, MD, PhD

Ana Oaknin, MD, PhD

In this setting, cytotoxic agents produce responses in just 10% of patients and median progression-free survival times of about 3 months. Given the cancer’s connection to the human papillomavirus, the potential for benefit from immune checkpoint inhibitors is of growing interest. In fact, pembrolizumab was approved by the U.S. Food and Drug Administration based on a response rate of 14% in patients with a PD-L1 Combined Positive Score ≥ 1.1 “But there is still room for improvement. More effective therapies for patients who have experienced disease progression on or after platinum-based therapy are needed,” Dr. Oaknin said.

According to her review of the study, innovaTV 204 did enroll a fairly representative population. Activity was seen for both squamous and adenomatous histologies, and with and without bevacizumab as prior treatment, but these findings need to be confirmed, she indicated.

Questions About Safety and Treatment Selection

Dr. Oaknin was concerned, however, about safety, especially regarding the adverse events of special interest. Ocular toxicity was recorded in 52% of patients, and grade 3 neuropathy was seen in 7%, “in a clinical trial population under a tight eye-care plan and with dose modifications,” she noted. “Therefore, a management plan must be instituted in daily clinical practice.”

Side to side with checkpoint inhibitors, added Dr. Oaknin, tisotumab vedotin appears to be comparable to pembrolizumab in activity, although the new agent is associated with more grade 3 or 4 adverse events and more treatment discontinuations.

“We are awaiting confirmatory phase III trials, which are mandatory,” Dr. Oaknin concluded. “What would be the second-line treatment if PD-1/PD-L1 agents are incorporated in first-line therapy after phase III trial results? Would tisotumab vedotin be the second-line therapy of choice? Would we see the same level of efficacy in a population already treated with immunotherapy? The next steps in the clinical development of tisotumab vedotin are crucial to find its best position in the metastatic and recurrent cervical cancer treatment landscape.”

DISCLOSURE: Dr. Oaknin has received fees for consulting and for reimbursement for travel expenses from AstraZeneca, Clovis Oncology, ImmunoGen, PharmaMar, Roche, and Tesaro.


1. Chung HC, Ros W, Delord JP, et al: Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: Results from the phase II KEYNOTE-158 study. J Clin Oncol 37:1470-1478, 2019.


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