Practical Advice on Sequencing Therapies and the Care of Cervical Cancer Patients


Closing out his discussion on the treatment of cervical cancer, Robert L. Coleman, MD, FACOG, FACS, provides thoughts on the optimal sequencing of therapy and importance of clinical trials.


Robert L. Coleman, MD, FACOG, FACS: With the incorporation of these new agents, we’ll continually refine our treatment approach to a patient who presents with recurrent metastatic disease. The biggest change that we might expect to happen is if these immune checkpoint inhibitors are adopted as adjuvant therapy. These would be in cohorts of patients who either don’t have metastatic disease, so we’re treating a risk, or in patients with metastatic disease and being used as primary and curative therapy. If these ongoing studies turn out to be positive, then it will vastly change what the treatment environment will be in the recurrent setting.

The primary issue that still needs to be addressed is the question of whether an immune checkpoint inhibitor is a one-and-done strategy. In other words, if you use it once, can you ever use it again? If the answer is yes, then the question is, can it be used again in the way it was initially studied or does it need to be given in combination? If so, what is the most appropriate combination? Would this be with chemotherapy? Would this be with other agents? Would it be with another immune checkpoint inhibitor, like the CTLA, PD-1, PD-L1 strategy? Or would it be used with other immune checkpoints such as TIGIT [T-cell immunoreceptor with immunoglobulin and ITIM domains]or OX40? There are several questions that are going to be raised as these drugs move to earlier lines of therapy.

As we know, most of these patients still with recurrent disease will ultimately need to go through multiple lines of treatment, so the adoption of agents like tisotumab vedotin and the expansion of that compound into our treatment algorithm will be important as well because this represents new opportunity for cytotoxic therapy. These cytotoxic therapies can be also informed by the addition of other agents, such as bevacizumab. That’s just the start of this.

When we think about sequencing, it’s a really important question because we have to start evaluating what the most effective therapy is and give it as early as possible. If it’s a 5-drug regimen for metastatic previously untreated patients, then that’s what we would need to do. If it’s efficacious there and has a label, we will use that as part of our standard of care to initiate therapy. That will inform whether downstream effects and agents will be appropriate or even an option. It continues to evolve, so we take each new indication and apply what we’ve learned from our previous study to see whether these are appropriate interventions when they’re needed.

Cervix cancer is an uncommon tumor. Many of the practitioners in the community may not see a lot of these patients, so it’s really important that everybody stay up to date as much as possible on the subtle changes in indication and the adoption of new therapy as it comes into the treatment domain. Educational opportunities abound for trying to make sure that everybody’s up to speed on the current state of the science. Fortunately, it’s evolving. Because we’ve had some wins, it’s translating into new potential options and avenues for investigation. Many of those are currently ongoing. I mentioned some already moving all the way up into the adjuvant setting for risk reduction, which is so exciting.

We also have other ways of activating the immune system, such as TIL [tumor-infiltrating lymphocyte]–based therapy. There are a number of very interesting immune conjugates, like antibody-drug conjugates, or bispecific types of antibodies. CRISPR [clustered regularly interspaced short palindromic repeats] cell therapy is already being adopted and implemented for this and other solid tumors. There’s a wealth of new potential options coming through the investigative channels. I make that strong plea that if you’re listening, to consider a clinical trial at every treatment decision. It may not be appropriate, but the only way we move the needle, and the only way we have moved the needle in this disease, has been because we’ve had gracious patients who have dedicated themselves to helping us understand it better and how we can ameliorate it and ultimately treat it, if need be. At every treatment decision, if it’s an option, please inquire for a protocol.

Transcript edited for clarity.

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