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

FDA apporval on tumor agnostic treatment 

Key Highlights

Our experts weigh in on some of the important topics and trends they anticipate to see this year at ASCO 2018 in Chicago.
In the final o f a series of blogs, Dr. Luis Mendoza and Dr. Forrest Anthony, both members of IQVIA's Therapeutic Science and Strategy Unit, discuss why immune checkpoint inhibitors are transforming cancer care.

Every year, oncology experts from across the globe come together at the American Society of Clinical Oncology’s (ASCO) annual meeting to share their latest developments in oncology research and discuss the next generation of therapeutic innovation. Over the past several years, many of these conversations and sessions have focused on advances in immuno-oncology – and immune checkpoint inhibitors (ICIs).
Immunotherapies, including immune checkpoint inhibitors are transforming cancer care. Instead of stimulating the immune system directly, ICIs block the brakes that tumors apply to the immune system so that immune system cells can continue to attack and kill cancer cells.  This medical innovation has delivered unprecedented value in the successful treatment of cancer patients, even where other treatments have failed. In its 2018 annual report, ASCO estimates that immune checkpoint inhibitors would “save 250,000 years of life if all US patients with advanced lung cancer for whom ICIs are currently indicated receive the treatment.” It also states that one in four newly diagnosed cancer patients, and one in 10 patients with previously treated disease, may live well beyond five years after treatment initiation thanks to ICIs.
The U.S. Food and Drug Administration (FDA) has already approved several immune checkpoint inhibitors to address nine different cancers, with several more in development. Among the most notable are two accelerated approvals granted last years for ICIs addressing microsatellite instability-high (MSI-H) colorectal and non-colorectal tumors.  Pembrolizumab was approved for the treatment of adult and children with unresectable or metastatic MSI-high or DNA mismatch repair deficient (dMMR) solid tumors; and nivolumab was approved for the treatment of patients 12 and older with dMMR and MSI-H metastatic colorectal cancer that has progressed following treatment.
The success of these two drugs is significant because they are the first ICIs approved on the basis of the genetic make-up of the tumor, rather than the specific tumor type or location. In other words, these indications are tumor-agnostic (also termed tissue-agnostic or site-agnostic) These advances in ICIs to treat MSI-H tumors are particularly notable because these tumors can have thousands of mutations and represent a significant percentage (10-30%) across a significant fraction of tumors. One of the studies for pembrolizumab included patients with 12 different tumor types using the same treatment, and 21% of those patients went into complete remission.
To date, pembrolizumab and nivolumab are the only two drugs to receive approvals based on a tumor’s biomarker status without regard to the tumor’s original tissue type or location. While these drugs are groundbreaking on their own, they also represent an exciting shift in the way oncology treatments can be developed, tested, and used to create opportunities for a single treatment to address multiple kinds of cancer. These approvals underscore the exciting advances being made in the arena of ICIs, and herald a new generation of oncology treatment based on tumor signature rather than tumor type. 

Let’s Connect at ASCO

We recently coauthored a white paper for IQVIA clients and clinical staff on how ICI tumor agnostic treatment approvals represent a promising new direction for oncology care. We and IQVIA experts are also looking forward to the ASCO meeting June 1-5 in Chicago, to discuss these and other oncology trends with peers from across the industry and to learn about innovations in oncology.
We know several speakers at the event will focus on trends in ICIs, including Dr. Gavin Dunn from the Washington University School of Medicine, who is giving an update on Checkpoint Inhibitors and Combinatorial Approach to Targeted Immunotherapies; and Dr. Jennifer Ann Wargo, from the University of Texas MD Anderson Cancer Center who will present on Novel Checkpoint/Targeted Therapy Combinations. We will also hear about some of the risks related to ICIs, including a presentation on Immune-Checkpoint Toxicity from Dr. Marc Ernstoff, of the Cleveland Clinic; and an education session on Primary and Acquired Resistance to ICIs.
The opportunity to hear these kinds of presentations and to talk with experts who’ve dedicated their careers to advancing oncology care is why ASCO is one of the most important events of the year. Researchers spend most of their time with their heads down, pursuing new treatment innovations, but oncology innovations don’t happen in a vacuum. By taking the time to come together at ASCO and other industry events we can share our successes, find new collaborations, and help drive innovation on behalf of all patients while ensuring the safety and efficacy of the trials we lead and the treatments that come to market. We look forward to seeing you there


More about our contributors

Forrest H. Anthony, MD, PhD

Forrest H. Anthony, MD, PhD, is Senior Director IQVIA Oncology Center of Excellence, North America. Dr. Anthony has more than 25 years’ experience in the biopharmaceutical industry. He works on customer drug development projects, and trains global staff to anticipate scientific innovations (e.g., immuno-oncology, Adoptive Cell Therapy, CAR-T therapies, oncolytic viruses).

 Luis Mendoza, MD, PhD

Luis Mendoza, MD, PhD, is Senior Medical Director of IQVIA’s Oncology-Hematology Therapeutic Science & Strategy Unit. Dr Mendoza joined IQVIA in 2015 after 20 years in the oncology medical practice combined with 12 years of experience in clinical development of different oncology compounds. Besides his clinical research experience with different anticancer monoclonal antibodies, immunomodulatory drugs, bi-specific monoclonal antibodies, oncolytic virus vaccines, cellular therapies etc and he has been focused leading clinical trials for novel checkpoint inhibitors and novel immunotherapies. Dr Mendoza is editorial board member of oncology-hematology journals and author of dozens of publications in peer-reviewed journals.

https://www.iqvia.com/blogs/2018/05/tumor-agnostic-immune-checkpoint-inhibitors