Pembrolizumab Granted FDA Approval for PD-L1+ Cervical Cancer

Pembrolizumab (Keytruda) has been granted an accelerated approval by the FDA for the treatment of patients with advanced, PD-L1–positive cervical cancer with disease progression on or after chemotherapy.

The approval is based on data from 98 patients with recurrent or metastatic cervical cancer enrolled in a single cohort in the phase II KEYNOTE-158 trial. The global, open-label, nonrandomized, multicohort, multicenter study evaluated pembrolizumab in patients with multiple types of advanced solid tumors who progressed on standard of care therapy.

At a median follow-up of 11.7 months (range, 0.6-22.7), the overall response rate (ORR) was 14.3% (95% CI, 7.4-24.1) in 77 PD-L1–positive patients (CPS ≥1) previously treated with ≥1 line of chemotherapy in the metastatic setting. The ORR comprised a complete response rate of 2.6% and a partial response rate of 11.7%. The median duration of response was not reached (range, 4.1-18.6+), and 91% of responders had a response duration of 6 months or longer.

There were no responses reported for patients with PD-L1 expression of CPS <1.

Among the 77 PD-L1–positive patients, the median age was 45 years (range 27-75), 32% had an ECOG performance status (PS) of 0, and 68% had an ECOG PS of 1. Eighty-one percent of patients were white, 14% were Asian, and 3% were black. Thirty-five percent of patients had 1 prior line of treatment for recurrent or metastatic disease, and 65% had ≥2 prior lines.

Regarding histology, 92% had squamous cell carcinoma, 6% had adenocarcinoma, and 1% had adenosquamous carcinoma. Ninety-five percent of patients had M1 disease and 5% had recurrent disease. PD-L1 status was determined using the PD-L1 IHC 22C3 pharmDx Kit.

The accelerated approval for pembrolizumab in this setting is contingent on the results of a confirmatory trial.

Pembrolizumab has additional approved indications in melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, urothelial carcinoma, gastric cancer, and microsatellite instability–high solid tumors.

Regorafenib Doubles 12-Month Survival Compared with Lomustine in Recurrent Glioblastoma Multiforme

Regorafenib (Stivarga) improved overall survival (OS) and progression-free survival (PFS) compared with lomustine (Gleostine) for patients with glioblastoma multiforme (GBM) that recurred following surgery and treatment with the Stupp regimen, according to updated results presented in a poster at the 2018 ASCO Annual Meeting.

Patients with histologically-confirmed GBM and documented disease progression were randomly assigned to 160 mg of daily regorafenib in a 3 weeks on, 1 week off schedule (n = 59) or 110 mg/m² of lomustine every 6 weeks (n = 60). Treatment continued until disease progression or unacceptable toxicity. Investigators performed brain MRIs every 8 weeks according to the RANO criteria to assess tumor response.

Updated findings from the randomized, multicenter, controlled open-label phase II REGOMA trial (NCT02926222) showed that the overall survival (OS) rate at 12 months favored patients assigned to regorafenib 38.9% vs 15.0%. The median OS was 7.4 months (95% CI, 4.7-7.3) in the regorafenib group compared with 5.6 months (95% CI, 4.7-7.3) in the lomustine arm (HR, 0.5; 80% CI, 0.38-0.65; P = .0007).

Thirty-three (55.9%) patients in the regorafenib arm experienced at least 1 grade 3/4 treatment-related adverse event (TRAE) compared with 24 (40%) in the lomustine arm. Those results are identical to findings first presented at the ESMO 2017 Conference in September. There were no treatment-related deaths recorded in either set of data.

Regorafenib could be the next treatment for recurrent glioblastoma and this trial could be important for the FDA to approve this drug as a second-line treatment for glioblastoma. In April 2017, the FDA approved regorafenib for the treatment of patients with hepatocellular carcinoma (HCC) who previously received sorafenib (Nexavar), based on findings from the phase III RESORCE trial.

https://www.targetedonc.com/news/regorafenib-doubles-12month-survival-compared-with-lomustine-in-recurrent-gbm