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Data from a phase 2 study presented during the 2020 ASCO Virtual Scientific Program demonstrated that Avastin (bevacizumab) in combination with Tarceva (erlotinib) was well tolerated and produced encouraging clinical outcomes in patients with advanced hereditary leiomyomatosis and renal cell carcinoma or sporadic papillary renal cell carcinoma.
Data from a phase 2 study presented during the 2020 ASCO Virtual Scientific Program demonstrated that Avastin (bevacizumab) in combination with Tarceva (erlotinib) was well tolerated and produced encouraging clinical outcomes in patients with advanced hereditary leiomyomatosis and renal cell carcinoma (HLRCC) or sporadic papillary renal cell carcinoma (RCC).
“Papillary RCC is the second-most common histologic subtype of kidney cancer and occurs in both familial and sporadic forms,” Dr. Ramaprasad Srinivasan, a principal investigator at the National Cancer Institute, said in a pre-recorded presentation of the data. “Patients with advanced papillary RCC exhibit poorer survival compared to their counterparts with clear cell RCC.”
A familial disorder, HLRCC predisposes patients to a version of early onset, aggressive papillary RCC. There are no data from prospective trials of systemic therapy and no established standard of care for these patients, according to Srinivasan.
To assess the safety and efficacy of Avastin in combination with Tarceva, Srinivasan and colleagues enrolled patients into two independent, parallel cohorts. Patients with HLRCC were placed into one study group and patients with sporadic papillary RCC were placed into the other.
Patients enrolling in the study could have received any number of prior therapies; however, they were restricted to two regimens of previous VEGF-targeting therapies. Additionally, patients could not have received any prior Avastin to treat their disease.
Both participants from the HLRCC (43 patients) and sporadic papillary RCC (40 patients) groups received Avastin at 10 mg/kg delivered intravenously every two weeks and Tarceva at 150 mg administered by mouth every day. Measuring the overall response rate, or the proportion of patients who experienced complete or partial responses to treatment, was the main goal of the study. Additional goals included measuring duration of response, as well as progression-free survival (PFS), or the time from the start of treatment until disease worsened.
More than half of the overall study population (45 patients; 54.2%) had a response to the combination therapy, most of which (43 responses) were partial in nature.
Patients in the HLRCC group had an overall response rate of 72.1% and patients in the sporadic papillary RCC group achieved an overall response rate of 35%.
Most patients (95%) within the HLRCC group experienced a decrease in their tumor burden, whereas 80% of patients in the other group had a decrease in tumor burden. The median time for disease to respond to therapy was 1.8 months, and the median duration of response was 19.3 months for patients in the HLRCC arm and 17.5 months in the sporadic papillary RCC arm.
The median PFS for the overall patient population was 14.3 months; however, there was a significant difference in median PFS when the HLRCC (21 months) and sporadic papillary RCC (8.8 months) groups were analyzed separately.
All patients reported experiencing some type of treatment-related side effect which, according to Srinivasan, was consistent with what has been reported in other studies involving this combination of therapies. Mild or moderate side effects included rash, diarrhea and dry skin. Nearly half (49%) of the patients experienced at least one serious or severe treatment-related side effect, commonly hypertension and proteinuria, increased levels of protein in the urine that can indicate kidney damage. One patient died of a gastrointestinal hemorrhage possibly related to Avastin.
“This is one of the largest studies of systemic intervention in patients with advanced papillary RCC and the first prospective study in HLRCC patients,” Srinivasan said.
The observed overall response rate and median PFS in patients with sporadic papillary RCC compared favorably to what would be expected with other available treatment options, according to Srinivasan.
“The combination of bevacizumab and erlotinib is a reasonable treatment option in patients with sporadic papillary RCC but might warrant additional study to define the optimal use in this group,” he concluded. “The combination is (also) highly active in patients with HLRCC, with an overall response rate of 72% and a median PFS of 21 months. Bevacizumab, in combination with erlotinib, should be considered the preferred option in this patient population.”