Michael Birrer, MD, PhD, UAB Comprehensive Cancer Center in Alabama, discusses checkpoint inhibitors for patients with endometrial cancer.

Across all tumor types, there is a growing excitement around checkpoint inhibitors, which is the case in endometrial cancer as well, explains Birrer. There is a subset of patients with endometrial cancers that are microsatellite instability-high (MSI-H).

Recently, there was an approval for MSI-H tumors; however, there is still a study investigating what the response rate is for patients with endometrial cancer since the approval was based on very few patients, states Birrer.

Videos

Dr. Birrer on Checkpoint Inhibitors for Endometrial Cancer

Michael Birrer, MD, PhD, director of Medical Gynecologic Oncology at Massachusetts General Hospital, discusses the prevalence of cervical cancer in the United States.

Cervical cancer is viewed as a rare tumor in the United States. There are about 8000 cases annually, with approximately 4800 deaths, Birrer says. Because of that, it is very difficult to get industry partners interested in the field for therapeutic developments. However, this disease requires funding and novel therapies for these patients.

From a worldwide perspective, there are several countries in which drugs will not be able to be developed in or have the funding for such agents. These are examples of the challenges ahead, he explains.

Dr. Birrer on Prevalence of Cervical Cancer in the United States

Michael Birrer, MD, PhD, director of Medical Gynecologic Oncology at Massachusetts General Hospital, discusses the challenges associated with the patient demographics of cervical cancer.

A majority of patients with cervical cancer are of underserved areas and likely do not have access to health care, Birrer explains. Moreover, this becomes a special population to treat. There are several inner-city medical centers that are stressed and overloaded with these patients, as well as those who come in for follow-up visits. At this point, many of these patients have advanced disease.

Even then, patients still fall through the cracks and are not optimally treated as a result of cultural, health, and insurance issues. This is because they prefer to avoid chemotherapy and radiation therapy. This is partly why this becomes a very difficult-to-treat population, he says.

Dr. Birrer on Challenges With Patient Demographics in Cervical Cancer

Michael Birrer, MD, PhD, director of Medical Gynecologic Oncology at Massachusetts General Hospital, discusses patient preferences for cervical cancer treatment, as well as the demographics of this population.

The cervical cancer patient population is very skewed to those of a minority population, Birrer explains. This is likely to do with sexual activity and lack of health care, or no access to health care. Therefore, this creates a very challenging population.

It is also possible, he adds, that these patients might also not regularly follow up on medical visits for their disease. Though they may undergo an initial visit and/or cervical cancer screening and a preinvasive lesion is detected, patients may not show up to their additional follow-up appointments to treat or monitor the cancer. Currenty, physicians and clinics do not have the infrastructure necessary to address these underserved populations, Birrer explains.

Dr. Birrer on Patient Preferences for Cervical Cancer Treatment

Michael Birrer, MD, PhD, director of Medical Gynecologic Oncology at Massachusetts General Hospital, discusses the FDA approval of rucaparib (Rubraca) for as a treatment for patients with 

-positive advanced ovarian cancer who have received at least 2 prior lines of chemotherapy.

The approval is based on data from 106 patients across 2 trials, including the ARIEL2 study. In a pooled analysis of data from the studies, the objective response rate (ORR) was 54% (95% CI, 44-64) with rucaparib.

The 106 patients comprised 42 patients from a phase I/II study (NCT01482715) and 64 patients from the ARIEL2 phase II study (NCT01891344). Both trials were multicenter, single-arm, open-label studies in patients with 

-positive ovarian cancer who had progressed on 2 or more prior chemotherapies.

The phase I/II trial included only platinum-sensitive patients, while ARIEL2 enrolled patients who were platinum sensitive, resistant, or refractory. The group of 106 patients had a median number of prior therapies of 3 and a median age of 59 years.

Michael Birrer, MD, PhD, director of Medical Gynecologic Oncology at Massachusetts General Hospital, discusses the FDA approval of rucaparib for as a treatment for patients with BRCA-positive advanced ovarian cancer who have received at least 2 prior lines of chemotherapy.

Dr. Birrer on FDA Approval of Rucaparib in Ovarian Cancer

Michael Birrer, MD, PhD, director of Medical Gynecologic Oncology at Massachusetts General Hospital, discusses some of the novel treatment options that could be explored in the future treatment of patients with cervical cancer.

Birrer says future research in this field could explore combinations, such as immune checkpoint inhibitors plus antiangiogenic agents, as those are active in the cervix.

Some investigators have also considered looking into moving the immune checkpoint inhibitors upfront in pre-invasive disease. Birrer cites a hypothetical example of a patient who may have CIN 3, or carcinoma in situ, and if she is given 1 or 2 cycles of an immune checkpoint inhibitor, she could potentially avoid conization or hysterectomy. However, he says, this could be challenging because this patient population is still technically considered to be curable, so one must be careful in investigating such novel approaches.

Dr. Birrer on the Need for Novel Treatment Options in Cervical Cancer

Michael Birrer, MD, PhD, director of Medical Gynecologic Oncology at Massachusetts General Hospital, discusses some of the remaining challenges in treating patients with cervical cancer.

Essentially all cervical cancers could be entirely eliminated, according to Birrer, as the HPV vaccine is widely available. Surprisingly, despite its accessibility, the vaccination rate in this country is quite low. Birrer hopes to see wider use of the vaccine in the near future.

In terms of treatment, Birrer briefly discusses a subset of patients whose tumors are still considered to be inoperable. These particular patients receive chemoradiation, which has shown efficacy, but for some, their tumors come back, and this can present many more difficulties for the overall course of treatment. A small percentage of these patients are candidates for exenteration, or complete surgical removal of the organ. However, Birrer strongly advises against this procedure, which he refers to as “horrific” in nature for patients, regardless of its ability to salvage.

Novel treatment options must also be investigated for patients who develop recurrent metastatic disease, says Birrer.

Dr. Birrer on Remaining Challenges in Cervical Cancer

Michael Birrer, MD, PhD, director of Medical Gynecologic Oncology at Massachusetts General Hospital, discusses recent advancements in cervical cancer.

The Gynecologic Oncology Group (GOG) 240 trial was an exciting breakthrough, says Birrer. It was the first randomized phase III trial that demonstrated a survival advantage in metastatic cervical cancer.

Cervical cancer is the poster child for immunotherapy, says Birrer. It is an HPV-driven tumor, similar to head and neck cancer, which has shown success with immunotherapy. The viral antigens are present in cervical cancer and there is a lot of potential for response or disease control, says Birrer.

A GOG small phase II immunotherapy has gone to completion, but responses may be low, says Birrer. However, immunotherapy trials are challenging. If immune RESIST criteria is not used the changes in tumor size can be misinterpreted as progression.

At Massachusetts General Hospital immunotherapy has been successful for some patients off-label, says Birrer. Some patients have had speculator responses, he adds.

Michael Birrer, MD, PhD

Articles