The US Food and Drug Administration’s (FDA) approvals of Merck’s Keytruda and Seagen and Genmab’s Tivdak this year were important milestones for the management of cervical cancer. Despite the rapidly changing treatment landscape, key opinion leaders (KOLs) interviewed by GlobalData have identified several needs that remain unmet in this disease setting. Addressing these unmet needs will require a multimodality approach.
Preservation of fertility is a significant unmet need in cervical cancer, with almost half of all patients being of child-bearing age. For patients with early-stage disease, fertility-sparing surgery may be an option, but this is not widely performed due to lack of training and an inability to identify suitable candidates for a conservative approach. The ConCerv trial showed promising outcomes in patients receiving fertility-sparing surgery and it is hoped that this strategy can be implemented with increased surgical training.
The lack of adjuvant therapy following chemoradiation for locally advanced disease results in around 50% of patients relapsing. On relapse, the prognosis is poor, with a very low probability of long-term survival. The KEYNOTE-A18 trial is currently investigating the addition of Keytruda to chemoradiation, while the CALLA study is investigating the addition of AstraZeneca’s Imfinzi to chemoradiation, both with a two-year maintenance period. KOLs believe this will address the unmet need in some patients, but adjuvant therapy for tumours that are insensitive to anti-PD-1/PD-L1 therapy is required.
Outside the US, there is a lack of treatment options for patients with distally metastatic or recurrent disease, when they progress on first-line chemotherapy and Avastin. There is currently no standard of care in the second line, with patients given chemotherapies with very little benefit or just the best supportive care. The approval of Keytruda and Tivdak outside the US would improve the outcome for patients.
Patients with PD-L1-positive tumours can be treated with Keytruda in the first or second line in the US. There are also multiple additional PD-1/PD-L1 inhibitors in the pipeline for cervical cancer as monotherapies and in combination with other agents. At present, these agents’ approval is limited to patients with PD-L1-positive tumours, leaving patients with PD-L1-negative tumours with limited treatment options. In addition, a significant proportion of patients fail to respond to immune checkpoint inhibition, requiring a different class of therapeutic.
The approval of Tivdak for the treatment of cervical cancer partially addresses this unmet need, but with an overall response rate (ORR) of 24%, this still leaves patients in need of additional treatment options. The approval of Iovance’s pipeline agent lifileucel could help address this unmet need, but the toxicity of the tumour-infiltrating lymphocyte (TIL) treatment regimen and the infrastructure required for personalised product preparation is likely to limit the number of patients who are suitable candidates for this therapy.
Almost all cervical cancers are caused by human papillomavirus (HPV) infections. There are three HPV vaccines currently approved by the FDA for the prevention of cervical cancer, making cervical cancer a vaccine-preventable disease. Unfortunately, vaccine uptake is poor across several markets (<1% in Japan, <19% in France, ~50% in the US and Spain), which will lead to the development of preventable cancers. KOLs have identified poor vaccine uptake to be due to inadequate public health campaigns, stigmas associated with sexually transmitted diseases, poor education and religious convictions. Increasing vaccine uptake is the greatest unmet need of all, as complete coverage of the population would prevent a very high percentage of cases.
Public health campaigns worldwide are aimed at increasing awareness of cervical cancer as a vaccine-preventable disease. The HPV vaccination’s inclusion in the childhood vaccination calendar, as well as the administration of vaccines in schools, is being used across the markets to increase vaccine uptake. The expansion of guidelines across markets to include male vaccination is also expected to reduce the levels of circulating HPV, driving down infection rates. Detailed coverage of the unmet needs in cervical cancer, as well as the pipeline agents set to address these needs, will be covered in the forthcoming report Cervical Cancer – Global Drug Forecast and Market Analysis to 2030.