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

Short fascinating and encouraging information where we are with the efficacy of the immuno-oncology (IO) agents: Potential 412k lives per year can be saved in China with the current mmunoOncology agents!

Great news for patients with BRAF-mutant malignant melanoma: A new combined treatment has been approved.  

Advanced BRAF-mutant melanoma is a serious and deadly type of skin cancer. Nearly half of melanoma patients who are diagnosed with the cancer after it has already spread have the BRAF mutation. Metastatic melanoma is the most life-threatening type of skin cancer and is associated with low survival rates. Approximately half of the estimated 200,000 new cases of melanoma diagnosed worldwide each year have BRAF mutations, a key target in the treatment of metastatic melanoma.

BRAFTOVI^TM (encorafenib) and MEKTOVI®(binimetinib) for the treatment of patients with unresectable or metastatic melanoma with a BRAF^V600E or BRAF^V600K mutation were approved by the FDA on June 27, 2018 based on clinical data from the Phase 3 COLUMBUS trial, published in the Lancet Oncology.

 

Fruquintinib prolongs survival in previously treated metastatic colorectal cancer

Fruquintinib significantly extended overall survival (OS) compared with placebo among adults with metastatic colorectal cancer who underwent at least two prior lines of chemotherapy, according to results of a randomized phase 3 study conducted in China.

“Although patients who progress after receiving two lines of systemic chemotherapy may still have good performance status, third-line treatment options are limited. There is, therefore, a strong unmet clinical need for treatment options in the third-line setting for metastatic colorectal cancer, especially in China.

Fruquintinib (Hutchison China MediTech Limited; Eli Lilly) is a vascular endothelial growth factor receptor inhibitor that blocks new blood vessel growth associated with tumor proliferation.

The phase 3 study conducted was double-blind, placebo-controlled, multicenter trial that included 416 Chinese adults (mean age, 54.6 years; 61.3% men) with metastatic colorectal cancer that had progressed after at least two lines of chemotherapy. Researchers randomly assigned 278 patients to receive 5 mg daily fruquintinib for 21 days, followed by 7 days off. The other 138 patients received placebo. Treatment continued until disease progression, intolerable toxicity or study withdrawal.

OS served as the primary outcome. Secondary outcomes included PFS, objective response rate and disease control rate. Patients assigned fruquintinib achieved significantly longer median OS (9.3 months vs 6.6 months; HR = 0.65; 95% CI, 0.51-0.83) and PFS (3.7 months vs. 1.8 months; HR = 0.26; 95% CI, 0.21-0.34). A higher percentage of patients assigned fruquintinib experienced grade 3 or grade 4 treatment-emergent adverse events (61.2% vs. 19.7%). Patients assigned fruquintinib appeared nearly three times as likely to experience serious adverse events (15.5% vs. 5.8%) and to require hospitalization (14.4% vs. 5.1%).

Standard treatment for metastatic colorectal cancer in China differs from that of Western countries, as only one-third of patients had undergone prior treatment with anti-VEGF or anti-EGFR antibodies.

https://www.healio.com/hematology-oncology/gastrointestinal-cancer/news/in-the-journals/%7B64f9b274-830c-4f39-8933-c127ac4d9e71%7D/fruquintinib-prolongs-survival-in-previously-treated-metastatic-colorectal-cancer