Roche presented detailed results at the European Society for Medical Oncology (ESMO) meeting from the Phase III IMpassion130 trial showing that intent-to-treat (ITT) patients who were given Tecentriq (atezolizumab) plus chemotherapy for the first-line treatment of triple-negative breast cancer achieved progression-free survival (PFS) of 7.2 months, versus 5.5 months for chemotherapy alone. Further, in the PD-L1-positive population, a subgroup determined by PD-L1 biomarker testing, median PFS was 7.5 months and 5 months, respectively, the company said.
"These important results in people with metastatic triple-negative breast cancer whose disease expresses the PD-L1 protein are highly encouraging and represent a significant step forward in the treatment of this challenging disease," said Sandra Horning, chief medical officer at Roche. Horning added that the company has shared the IMpassion130 results, which were simultaneously published in the NEJM, "with global health authorities with the hope of bringing this Tecentriq combination to people with PD-L1-positive, metastatic triple-negative breast cancer as soon as possible."
IMpassion130 enrolled 902 patients with unresectable locally advanced or metastatic triple-negative breast cancer who have not received prior systemic therapy for metastatic breast cancer. The PD-L1-positive population consisted of 369 patients from the overall group. Participants were randomised to receive Tecentriq plus Celgene's Abraxane (nab-paclitaxel) or placebo plus Abraxane. Aside from investigator-assessed PFS, the other co-primary endpoint was overall survival (OS).
Roche reported that median OS in the ITT population was 21.3 months among patients in the Tecentriq group, compared with 17.6 months for placebo, which was not statistically significant at the interim analysis. However, the company said the interim analysis revealed a clinically meaningful 9.5-month OS improvement in the PD-L1-positive population, where respective OS results were 25 months versus 15.5 months. "Due to the hierarchical statistical design, results in the PD-L1-positive population were not formally tested," Roche explained, adding that follow-up will continue until the next planned analysis. Still, Horning said the company is optimistic as "it's really extraordinary to see a survival benefit of any kind in triple-negative breast cancer. We're quite excited about the degree of effect."
Secondary endpoints included objective response rate (ORR), duration of response and time to deterioration. The company stated that the rate of ORR among Tecentriq-treated patients in the ITT population was 56 percent, versus 46 percent for chemotherapy, while the respective rates in the PD-L1-positive subgroup were 59 percent and 43 percent. Roche indicated that none of the ORR results were significant.
The Swiss drugmaker also said that safety in Tecentriq-plus-Abraxane arm "appeared consistent" with the known safety profiles of the individual medications, and no new safety signals were identified with the combination.
Tecentriq is already approved in the EU, US and more than 80 countries for previously treated, metastatic non-small-cell lung cancer and for certain types of untreated or previously treated metastatic urothelial carcinoma. The PD-L1 inhibitor, which costs $12 500 a month, saw sales rise 50 percent over the first nine months to 524 million Swiss francs ($528 million). However, Daniel O'Day, head of pharmaceuticals at Roche, suggested that marketing Tecentriq to the PD-L1-positive population in triple-negative breast cancer could generate as much as 1 billion Swiss francs ($1 billion) in annual sales. He indicated that Roche will take another look at the data next year for an update on how long patients lived.
According to Roche, triple-negative breast cancer accounts for about 15 percent of all breast tumours, while about 40 percent of patients with triple-negative breast cancer will test positive for the PD-L1 protein, making them potentially eligible to use Tecentriq, if it eventually gains approval in this population. For related analysis, see ESMO 2018 analysis: Roche delivers an immunotherapy breakthrough in triple negative breast cancer albeit in a narrowed patient population.
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