Robert L. Coleman, MD, FACOG, FACS, chief scientific officer of The US Oncology Network, discusses the FDA approval of tisotumab vedotin-tftv (Tivdak) in recurrent or metastatic cervical cancer. 

FDA granted an accelerated approval to tisotumab vedotin

 for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. The approval was based on findings from the phase 2 innovaTV 204 trial (NCT03438396), in which the antibody-drug conjugate induced a 24% objective response rate in patients with recurrent or metastatic cervical cancer who previously received doublet chemotherapy and bevacizumab (Avastin). 

Tisotumab vedotin provides another treatment option to patients with recurrent or metastatic cervical cancer, says Coleman. Historically, very few treatment options have demonstrated efficacy in this patient population, including immunotherapy, Coleman explains. Although a proportion of patients respond well to immunotherapy, the majority of patients with cervical cancer will not benefit from this treatment approach, Coleman adds.

As such, tisotumab vedotin offers an option for patients with cervical cancer who need an effective therapy that acts rapidly, concludes Coleman.

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Robert L. Coleman, MD, FACOG, FACS, discusses the FDA approval of tisotumab vedotin in recurrent or metastatic cervical cancer.  



Dr. Coleman on the FDA Approval of Tisotumab Vedotin in Recurrent or Metastatic Cervical Cancer 

Robert L. Coleman, MD, FACOG, FACS, professor and Ann Rife Cox Chair in Gynecology, Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, The University of Texas MD Anderson Cancer Center, discusses the next steps of treatment for patients with high-grade serous ovarian cancer.

Since there has been an earlier exposure of PARP inhibitors to ovarian cancer, the field is evolving rapidly, says Coleman. Physicians are interested in looking at other FDA-approved drugs in high-grade serous ovarian carcinoma in combination with other agents, such as anti-angiogenesis agents and checkpoint inhibitors, in the recurrent space.

For example, the PARP inhibitor veliparib is being explored in combination to determine how the agent best fits in the recurrent ovarian cancer space. In the phase III VELIA trial evaluated veliparib in combination with chemotherapy in patients with advanced ovarian cancer. There is much work to be done regarding PARP inhibitors overall, Coleman concludes.

Robert L. Coleman, MD, discusses the next steps of treatment for patients with high-grade serous ovarian cancer.
 

Dr. Coleman on Next Treatment Steps for Patients With Ovarian Cancer

Robert L. Coleman, MD, FACOG, FACS, professor, Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, discusses advances made in the treatment of ovarian cancer.

The field of ovarian cancer has undergone a rebirth, says Coleman, as pharmaceutical companies and investigators work to bring new drugs into the treatment paradigm. One of the first big successes was seen with the accelerated approval of the PARP inhibitor olaparib (Lynparza), which was initially just a treatment for a highly selected group of patients, he explains. Now, the agent has indications as a maintenance treatment as well as first-line maintenance. Since olaparib, 2 other PARP inhibitors have been awarded FDA approvals as well: rucaparib (Rubraca) and niraparib (Zejula). All of this progress has been seen in a relatively short period of time, he adds.

From there, other drugs began to enter into the market, both single agents and combination treatments. For example, several ongoing trials are evaluating the use of angiogenesis agents in combination with PARP inhibitors. There are also some new chemotherapy agents being explored, namely antibody drug conjugates. Rituximab (Rituxan) is one that is furthest along in development, says Coleman.

He adds that immunotherapy agents are also making headway in the space. Although many trials have failed to demonstrate significant efficacy with single agents, investigators are exploring several combination regimens comprised of immunotherapy agents and either PARP inhibitors or angiogenesis agents. There are several trials ongoing right now, says Coleman, that are evaluating these regimens in both the frontline and recurrent setting.

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Dr. Coleman on Advances Made in Ovarian Cancer Treatment

Robert L. Coleman, MD, FACOG, FACS, professor, Ann Rife Cox Chair in Gynecology, Department of Gynecologic Oncology and Reproductive Medicine, vice chair, Clinical Research, The University of Texas MD Anderson Cancer Center, discusses the next steps following results of the ARIEL2 trial, which aimed to identify patients with ovarian cancer most likely to respond to rucaparib using tumor genetic analysis.

This research was used as a prospective decision tool that will also be implemented in the ongoing ARIEL3 trial, which will stratify patients based on their genomic score, 

 mutation status, and loss of heterozygocity (LOH) score. The discovery of genomic “scarring” caused by homologous recombination deficiency as a biomarker in ARIEL2 will help move the next trial forward, Coleman explains. ARIEL2 will also be expanded to include more heavily pretreated patients.

To further improve the response rate, researchers are tweaking the trial design. Coleman says that even all 

-mutant patients did not respond to rucaparib. Also, in 

 wild-type patients with a high degree of LOH, not all aberrant genes translated into response. These findings allow researchers to determine that not all genes involved in the pathway are representative of synthetic lethality.

Robert L. Coleman, MD, The University of Texas MD Anderson Cancer Center, discusses the next steps following results of the ARIEL2 trial, which aimed to identify patients with ovarian cancer most likely to respond to rucaparib using tumor genetic analysis. 


Dr. Coleman on Next Steps Following ARIEL2 Trial for Ovarian Cancer

Robert L. Coleman, MD, FACOG, FACS, professor, Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, discusses how bevacizumab could be effective in tumor types beyond ovarian cancer.

Bevacizumab, Coleman explains, has the potential to be added to chemotherapy. Unanswered questions surrounding bevacizumab, however, regard the understanding of mechanisms that drive its resistance, what therapies it could be combined with, and selecting patients who will have maximum benefit.

Bevacizumab has unique effects in the microenvironment; different dosages will have varying effects, Coleman adds.

Previous data show that in the immune phenotype of the ovarian cancer patient population, bevacizumab may be necessary for an appropriate treatment plan.

However, Coleman cautions, even with bevacizumab, the one-drug-treats-all mindset should not be used.

Robert L. Coleman, MD

Articles

Dr. Coleman on the FDA Approval of Tisotumab Vedotin in Recurrent or Metastatic Cervical Cancer

Dr. Coleman on Next Treatment Steps for Patients With Ovarian Cancer

Dr. Coleman on Advances Made in Ovarian Cancer Treatment

Dr. Coleman on Next Steps Following ARIEL2 Trial for Ovarian Cancer

Dr. Coleman on Bevacizumab Across Tumor Types