Kevin Wright

Treatment with Bavencio (avelumab) prevented relapse in women with gestational trophoblastic tumors (GTT) that were resistant to single-agent chemotherapy, according to results of a study presented during the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting.

Results from the small phase 2 study, which is the first trial to explore the use of immunotherapy in patients with GTT, demonstrated that 53% of patients responded to therapy, suggesting that Bavencio may be a new therapeutic option for these patients.

"This proof-of-concept study shows that treatment with the immunotherapy avelumab works against these tumors when resistance to single-agent chemotherapy develops,” said lead study author Dr. Benoit You, of the Centre Hospitalier Lyon-Sud and Lyon Investigational Center for Treatments in Oncology and Hematology in France, in a press release. “Although more evidence is needed before changing clinical practice, these are highly promising results, suggesting that avelumab could prevent patients with chemo-resistant disease from the

severe toxicity of chemotherapy combinations.”

Over the span of two years, 17 patients were enrolled in the trial. Of those, 15 patients were treatable and assessable. Successful normalization of human chorionic gonadotropin (hCG), a hormone produced primarily by certain cells of the placenta during pregnancy, was reached in 53% of patients, leading to discontinuation of Bavencio. There was no sign of disease relapse in any of the patients after 29 months of follow up. Researchers consider patients who reach 12 months disease free with no relapse to be cured.

Patients whose disease was resistant to monochemotherapy (cohort A) or to polychemotherapy (cohort B) received Bavencio intravenously at 10&#8197;mg/kg every two weeks. The study drug was administered until hCG normalization, and for three additional cycles thereafter.

The remaining seven patients had a resistance to Bavencio. Those patients were managed with chemotherapy, either with or without surgery.

One patient who reached hCG normalization from the study developed a normal pregnancy and delivered a healthy baby one year after discontinuing treatment.

“This is the first report of a normal pregnancy in a patient previously cured from her tumor with immunotherapy,” said You in pre-recorded presentation.

“This provides reassuring data about the impact of immunotherapy on subsequent fertility.”

The investigators reported a satisfactory safety profile for Bavencio, with no severe side effects reported. The most common side effects included fatigue (33%), nausea-vomiting

(33%), infusion-related reactions (27%), thyroid disorder (20%), dry eyes (20%), and diarrhea (20%). One patient reported a uterus bleed, but it was not related to treatment.

GTTs are rare, abnormal growths in the uterus that develop from the placenta during conception and show an overexpression of programmed death-ligand 1 (PD-L1) proteins. Bavencio inhibits PD-L1, making it a reasonable alternative to chemotherapy for patients with these tumors.

The researchers are currently conducting a similar trial for Bavencio in the first-line setting, treating low-risk tumors with methotrexate and Bavencio before resistance can develop. “The objective is to cure 95% of patients,” You said during a press briefing. “With methotrexate, we estimate that we can cure 70% of patients. What we expect is that with the combination with avelumab, we will be able to cure 95% of patients.”

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“Although more evidence is needed before changing clinical practice, these are highly promising results, suggesting that (Bavencio) could prevent patients with chemo-resistant disease from the severe toxicity of chemotherapy combinations.”

Bavencio May Be Effective in Preventing Relapse in Women With Gestational Trophoblastic Tumors

Fotivda (tivozanib) significantly improved survival, compared with Nexavar (sorafenib), in patients with highly relapsed or refractory metastatic renal cell carcinoma (RCC), according to results from the phase 3 TIVO-3 trial presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.

“We believe the TIVO-3 data demonstrate a favorable risk/benefit profile for tivozanib in the growing population of patients who have relapsed or become refractory to multiple lines of therapy, including checkpoint inhibitors,” Dr. Sumanta Pal, associate clinical professor in the Department of Medical Oncology and Therapeutics Research and co-director of the Kidney Cancer Program at City of Hope Comprehensive Cancer Center, said in a press release.

An updated analysis of the data found that with a median follow-up of 38 months for Fotivda and 40 months for Nexavar, median overall survival was 16.4 months and 19.2 months, respectively. A subset analysis showed the greatest benefit was derived by the cohort of patients that had received treatment with a prior checkpoint inhibitor and VEGF inhibitor.

Previously released data also showed an increased median progression-free survival (the time from treatment to disease worsening) for Fotivda when compared with Nexavar.

“The lack of clinical data to guide treatment decisions in a robust, evidence-based manner in this setting is a serious and growing unmet medical need, particularly as this population continues to grow thanks to improved treatment in earlier lines,” Pal added. “TIVO-3 provides the first positive superiority study to help guide this important treatment decision and, furthermore, offers this highly refractory patient population a favorable tolerability profile as indicated by fewer dose reductions, interruptions and discontinuations over a less selective VEGFR TKI in sorafenib.”

The TIVO-3 study was a controlled, multicenter, open-label, phase III trial which randomized 350 patients with highly refractory metastatic RCC who had failed two or more prior regimens, including VEGF-TKI treatment, 1:1 to receive either oral Fotivda or Fotivda. Crossover between arms was not permitted.

Eighteen percent of patients in the Fotivda arm achieved partial response, compared with 8% of those in the Fotivda arm. The objective response rate was 34% and 24%, respectively.

Treatment with Fotivda was found to be generally well-tolerated, and the safety profile was favorable when compared with Nexavar. Treatment-related side effects were reported in 84% of patients receiving Fotivda and 94 of those receiving Nexavar. Serious treatment-related side effects occurred in 11% of patients treated with Fotivda versus 10% of patients who received Nexavar.

The most common grade 3 or 4 side effects reported in patients receiving Fotivda and Nexavar was hypertension (21% vs 14%, respectively). The most commonly reported any grade side effects associated with Fotivda were hypertension (38%), diarrhea (33%), fatigue (29%) and decreased appetite (27%).

The investigators reported significantly reduced dose reductions and interruptions due to side effects for Fotivda versus Nexavar (48% vs 63%), despite nearly double the average time of cycles initiated for the tivozanib arm (11.9 months vs 6.7 months, respectively). Treatment related side effects leading to permanent discontinuation were 8% for Fotivda compared with 15% for Nexavar.

“The biggest advantage to tivozanib is tolerability,” Dr. Brian Rini, from Vanderbilt-Ingram Cancer Center, said in a recent interview with 

 “One thing where my mindset has changed now that we have immune therapy combinations that can be curative, is that when we are using single agent TKIs, we’re really just trying to control disease. Because we’re not curing those patients, and they can be on (TKI therapy) for many months or years, tolerability is really the key thing.”

Rini added that these findings support the use of another VEGF TKI in this patient population. “Patients, appropriately, always want more options,” he said. “…Having tolerable options, especially in this late line setting, is a potential advantage to patients. I often describe to patients that we’re just trying to get as many shots on goal as possible…So, I think it adds to our weapons in this disease.”

When compared with Nexavar, Fotivda showed improved progression-free survival, and a more manageable safety profile for patients with relapsed or refractory metastatic renal cell carcinoma.

Kevin Wright

Bavencio May Be Effective in Preventing Relapse in Women With Gestational Trophoblastic Tumors

Fotivda Improves Survival in Relapsed, Refractory Metastatic Renal Cell Carcinoma

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