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by: Samuel Petrequin, Associated Press

The U.N. General Assembly adopted a resolution in 2005 establishing the annual commemoration, and chose Jan. 27 the day that Auschwitz-Birkenau was liberated by Soviet troops in 1945. FILE People are seen arriving at the site of the Auschwitz-Birkenau Nazi German death camp, where more than 1.1 million were murdered, in Oswiecim, Poland, Jan. 27, 2020. A new Polish foundation has been created to distribute grants globally to groups that come up with novel ways to fight indifference to hatred and discrimination. The Auschwitz Pledge Foundation was announced on Wednesday, Jan. 26, 2022 on the eve of the 77th anniversary of the liberation, by Soviet forces in 1945, of the World War II Nazi death camp in German-occupied Poland. (AP Photo/Czarek Sokolowski, File)

BRUSSELS (AP) European Union lawmakers will observe a minutes silence Thursday and welcome a centenarian Holocaust survivor as the world remembers Nazi atrocities and commemorates the 77th anniversary of the liberation of the Auschwitz concentration camp.

Margot Friedlander will address the EU Parliament as part of the commemorations of International Holocaust Remembrance Day.

The U.N. General Assembly adopted a resolution in November 2005 establishing the annual commemoration and chose Jan. 27 the day that Auschwitz-Birkenau was liberated by Soviet troops in 1945.

Due to the coronavirus pandemic, many International Holocaust Remembrance Day commemorations Thursday will be held online this year again. A small ceremony, however, will take place at the site of the former Auschwitz death camp, where World War II Nazi German forces killed 1.1 million people in occupied Poland. The memorial site was closed earlier in the pandemic but reopened in June.

In all, about 6 million European Jews and millions of other people were killed by the Nazis and their collaborators during the Holocaust. Some 1.5 million were children.

The 100-year-old Friedlander was arrested in 1944 while on the run and brought to the Theresienstadt concentration camp in what is now the Czech Republic. A year before, her mother and brother were deported to Auschwitz, where they were both killed.

Friedlander and her husband immigrated to the U.S. in 1946 and returned to Berlin in 2010. She has since been traveling around Germany to tell the story of her life and promote remembrance.

Charles Michel, the head of the EU Council bringing together leaders of the 27 EU member countries, insisted on the importance of commemorating the Shoah as the number of survivors diminishes every year.

With each passing year, the Shoah inches towards becoming a historical event, Michel said. More and more distant, more and more abstract. Especially in the eyes of the younger generations of Europeans. This is why, paradoxically, the more the years go by, the more important the commemoration becomes. The more essential.

Commemorations are taking place amid a rise of antisemitism that gained traction during lockdowns as the pandemic exacerbated hatred online.

To tackle Holocaust denial, UNESCO and the World Jewish Congress launched a partnership Thursday with the online platform TikTok popular with youngsters. They say it will allow users to be oriented toward verified information when searching for terms related to the Shoah.

According to the U.N., 17% of content related to the Holocaust on TikTok either denied or distorted the Holocaust.

Denying, distorting or trivializing the true facts of the Holocaust is a pernicious form of contemporary antisemitism, said UNESCO Director-General Audrey Azoulay. All online platforms must take responsibility for the spread of hate speech by promoting reliable sources of information.

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Holocaust survivor honored as world observes 77th anniversary - WETM - MyTwinTiers.com

On 24 and 25 January 2022, the EU ministers responsible for higher education, research and innovation met in Paris, in the context of the French Presidency of the Council of the European Union

They met at the Cit des Sciences et de lIndustrie at the invitation of the Minister of Higher Education, Research and Innovation, Frdrique Vidal. The ministers discussed the future of universities for Europe, and the need in this regard to better combine European policies for higher education, research and innovation.

At a first discussion with professors from the Collge de France, the ministers reiterated the need for transformation in the sector of European higher education so as to respond to existing and future challenges, particularly the green and digital transitions. The ministers also affirmed their intention to support establishments in the process of transformation in order for them to contribute to the major priorities of the EU, such as the European Green Deal, digital decade and industrial strategy.

The ministers also underscored the international dimension of European policy regarding higher education, research and innovation and the importance of cooperating with third countries. With the aim of ensuring a safe and conducive environment for the work of students and international researchers, the ministers recognised the need to promote balanced and reciprocal collaboration with third countries based on shared principles and values.

Lastly, the ministers discussed strengthening inter-university cooperation in Europe, on the basis of the recent proposals made on 18January2022 by the European Commission: a European Strategy for Universities and a proposal for a Council Recommendation on building bridges for effective European cooperation in higher education. The ministers pledged full support to alliances such as European Universities and recognized the need to make further progress for the benefit of the entire European sector of higher education, in particular by working towards a unique legal statute to allow universities to deliver European degrees, jointly recruit the best researchers and students at international level and establish joint structures such as state-of-the-art laboratories.

In this respect, the ministers committed to begin work in the coming months to remove the barriers facing alliances such as European Universities, by providing them with a set of instruments and contributing towards securing their future by exploiting synergies between European, national and regional financing mechanisms.

Last reviewed on 26 January 2022

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Informal Meeting of European Ministers Responsible for Higher Education, Research and Innovation - French Presidency of the Council of the European...

The European Parliaments internal mid-term elections will conclude this week, when all twenty standing committees and the three subcommittees will elect their chair and up to four vice-chairs for the remainder of the legislature.

Swedish centre-right MEP Tomas Tob (EPP) who is standing for reelection as chair of the Committee on Development (DEVE) told the Parliament Magazine in an interview in November about this unique practice:

This mid-term reshuffle, where everything is up in the air again, is quite interesting and something perhaps for national parliaments to also think about. Its good because it keeps people on their toes.

The DEVE committee will take its turn on Wednesday morning, as will the committees on Civil Liberties, Justice and Home Affairs (LIBE), Legal (JURI) and Constitutional (AFCO) affairs, Culture and Education (CULT) and the two subcommittees on Security and Defense (SEDE) and Human Rights (DROI).

Their parent committee, on Foreign Affairs (AFET) will have opened the procedures on Monday lunchtime, with the others following suit that day and on Tuesday.

This mid-term reshuffle, where everything is up in the air again, is quite interesting and something perhaps for national parliaments to also think about. Its good because it keeps people on their toes.

Tomas Tob, MEP

Apart from the elections, many committees are also pursuing their work agendas. The Committee on Budgetary Control (CONT) is continuing its 2020 EU budget discharge procedure with a joint debate on no less than 18 reports on different aspects of the budget on Tuesday morning.

At least six committees will host French government ministers in charge of their area to be informed about the priorities of their Council Presidency, starting with the Committee on Employment and Social Affairs (EMPL) and the Committee on International Trade (INTA) on Monday afternoon.

The most important legislative work will arguably be done in a joint session of the Internal Market (IMCO) and Civil Liberties (LIBE) committees who will hold a first debate on the Artificial Intelligence (AI) Act on Tuesday, with Parliaments rapporteurs Brando Benifei, head of the Italian S&D Group delegation for IMCO, and Renew Groups Vice-Chair Drago Tudorache (RO) for LIBE in the lead, and the European Commission participating.

When he was appointed rapporteur in early December, Tudorache sketched out his overall goals on Twitter:

In another joint meeting, the committees on the Environment, Public Health and Food Safety (ENVI) and on Agriculture and Rural Development (AGRI) are hoping to illuminate one of the EUs current flagship projects, the Farm to Fork Strategy, in particular its impact on agriculture and food systems on Tuesday late afternoon. Four experts who have recently published studies on the matter will share the results of their research in a public hearing.

And yet another special committee of this legislatures first term, this time the one on Foreign Interference in all Democratic Processes in the European Union, including Disinformation (INGE) is nearing its conclusion with the final committee vote on its report, drafted by the EPP Groups Vice Chair Sandra Kalniete.

Writing for the Parliament Magazine in November, the veteran Latvian legislator called for a strengthening of a wide range of defense mechanisms, from monitoring and analysing disinformation to creating more transparency on non-EU investment to avoid elite capture and ensuring durable and transparent funding of independent investigative journalism.

Regulation alone will not do, Kalniete argued:

It is a pipe dream to expect legislation to keep pace with the development of disruptive technologies, which is why our focus must lie on building an overall resilience base.

After its elections, the Committee on Womens Rights and Gender Equality (FEMM) will prepare a critical view for Parliament on itself for the next plenary session by adopting its 2020 annual report on Gender Mainstreaming in the European Parliament on Tuesday, drafted by two French MEPs, Irne Tolleret (Renew) and Gwendoline Delbos-Corfield (Greens/EFA).

And the AFET committee will hold the final vote on an own-initiative report on another subject close to Parliaments heart at the end of its Tuesday morning sitting, Renew Groups Vice Chair Katalin Czehs (HU) report on corruption and human rights.

Parliament will end the week with a special plenary session on Thursday, International Holocaust Remembrance Day, 77 years to the day after the liberation of Auschwitz.

President Roberta Metsola is to open the event and centenarian Holocaust survivor Margot Friedlnder to address the house.

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This Week in the European Parliament - The Parliament Magazine

BERLIN The United States and its NATO allies are moving to bulk up their military commitments in the Baltics and Eastern Europe as the standoff with Russia over Ukraine deepens.

Denmark is sending fighter jets to Lithuania and a frigate to the Baltic Sea. France has offered to send troops to Romania. Spain is sending a frigate to the Black Sea. President Biden has put thousands of U.S. troops on high alert.

And then there is Germany. In recent days Germany Europes largest and richest democracy, strategically situated at the crossroads between East and West has stood out more for what it will not do than for what it is doing.

No European country matters more to European unity and the Western alliance. But as Germany struggles to overcome its post-World War II reluctance to lead on security matters in Europe and set aside its instinct to accommodate rather than confront Russia, Europes most pivotal country has waffled in the first crucial test for the new government of Chancellor Olaf Scholz.

Germanys evident hesitation to take forceful measures has fueled doubts about its reliability as an ally reversing the dynamic with the United States in recent years and added to concerns that Moscow could use German wavering as a wedge to divide a united European response to any Russian aggression.

President Biden held a video call with European leaders on Monday night, saying it went very, very, very well, and beforehand Chancellor Scholz reiterated that Russia would suffer high costs in case of a military intervention. But Germanys allies have still been left to wonder what cost it is prepared to bear to confront possible Russian aggression.

Within the European Union Germany is crucial to achieve unity, said Norbert Rttgen, a senior conservative lawmaker and advocate of a more muscular German foreign policy. Putins goal is to split the Europeans, and then split Europe and the U.S. If the impression prevails that Germany is not fully committed to a strong NATO response, he will have succeeded in paralyzing Europe and dividing the alliance.

As Russia held military drills near the Ukrainian border on Tuesday, Mr. Scholz met with President Emmanuel Macron of France in Berlin, warning Moscow that a military aggression calling into question the territorial integrity of Ukraine would have grave consequences.

But the German government has not only ruled out any arms exports to Ukraine it is also holding up a shipment of nine Communist-era howitzers from Estonia to Ukraine.

Mr. Scholz and other senior Social Democrats in his government and party have been vague about whether shuttering the controversial Nord Stream 2 undersea gas pipeline from Russia to Germany would be part of an arsenal of possible sanctions against Russia, insisting it was a private -sector project and one separate from Ukraine.

Friedrich Merz, the designated new leader of Angela Merkels opposition conservative party, meanwhile, has warned against excluding Russian banks from the Swift payment transactions network, which handles global financial transfers, because it would harm Germanys economic interests.

Germanys muddled stance has been especially unsettling to Ukraine and some of Germanys eastern neighbors. The Ukrainian foreign minister, Dmytro Kuleba, accused Berlin of effectively encouraging Russian aggression. Other were no less scathing.

Berlin is making a big strategic mistake and putting its reputation at risk, Laurynas Kasinas, chairman of the national security committee of the Lithuanian Parliament told the public broadcaster LRT.

Artis Pabriks, Latvias defense minister, said these days German deterrence was not sending weapons to Ukraine, but a field hospital.

The strain in the alliance came to a head last weekend when the chief of the German Navy said that President Vladimir V. Putin of Russia deserved respect and that Crimea would never be returned to Ukraine. Vice Adm. Kay-Achim Schnbach, resigned, but the backlash was swift and emotional.

This patronizing attitude subconsciously also reminds Ukrainians of the horrors of the Nazi occupation, when Ukrainians were treated as subhuman, said Andriy Melnyk, Ukraines ambassador to Germany.

Washington has been at pains to publicly stress its trust in Berlin, while privately lobbying Mr. Scholz to take a harder line.

President Biden sent several emissaries to Berlin. William J. Burns, head of the C.I.A., presented the chancellor with the latest intelligence on Ukraine. Secretary of State Antony J. Blinken, who stopped in Berlin before meeting his Russian counterpart in Geneva last week, said on Sunday he had no doubts over Germanys determination to stand up to Russia.

It is telling that the U.S. has to publicly reaffirm its trust in Germany, Jana Puglierin of the Berlin-based European Council on Foreign Relations said. That used to be a given.

The wrenching debate over where precisely German loyalties lie is not new. Russian-German relations have been shaped by centuries of trade and cultural exchange but also two World Wars. The Cold War added yet another layer of complexity: West Germany became firmly embedded in the Western alliance while East Germany lived under Soviet occupation.

Why do we see Russia differently from the Americans? History, said Matthias Platzeck, chairman of the Russian-German Forum and a former chair of Mr. Scholz Social Democrats. Germany and Russia have been linked for a thousand years. The biggest Russian czarina was Catherine the Great, a German, who incidentally made Crimea part of Russia.

We attacked Russia twice, and the second time it was a genocidal war, he added. Twenty-seven million Soviets died, 15 million Russians among them.

Ominous warnings. Russia called the strike a destabilizing act that violated the cease-fire agreement, raising fears of a new intervention in Ukraine that could draw the United States and Europe into a new phase of the conflict.

The Kremlins position. President Vladimir V. Putin of Russia, who has increasingly portrayed NATOs eastward expansion as an existential threat to his country, said that Moscows military buildupwas a response to Ukraines deepening partnership with the alliance.

That does not mean that Germany has failed to stand up to Russia in recent years. Germany commands a multinational NATO battle unit in Lithuania and helps monitor Baltic airspace for Russian interference. It is planning to send fighter jets to Romania next month to do the same there. (And yes, it is also sending a field hospital to Kyiv next month.)

In 2014, when Mr. Putin invaded Ukraine and annexed Crimea, it was Ms. Merkel who rallied neighboring countries in East and West to back tough sanctions on Russia.

But the change of German leadership after 16 years of Ms. Merkel has put in place a government that is divided on how hard a line to draw with Russia.

Mr. Scholzs Social Democrats have traditionally favored a policy of working with the Russians. In the 1970s, Chancellor Willy Brandt engineered the policy of rapprochement with Moscow during the Cold War, while the last Social Democratic chancellor, Gerhard Schrder, is not just a close friend of Mr. Putin (he celebrated his 70th birthday with him) but has been on the payroll of Russian energy companies since 2005.

The new Green Party foreign minister, Annalena Baerbock, has been more outspoken on being tougher on Russia. But even she has drawn a line on sending German arms to Ukraine, citing history.

The arms-export policy in many ways embodies the modern German paradox of a nation that knows it has to assume more leadership responsibility in the world but is not quite ready to act that way.

The idea that Germany delivers weapons that could then be used to kill Russians is very difficult to stomach for many Germans, said Marcel Dirsus, a political analyst and nonresident fellow at the Institute for Security Policy at Kiel University.

The government has been even more divided over Nord Stream 2, a gas pipeline owned by Gazprom, Russias state-owned energy company, that many fear will hand Mr. Putin an easy way to exert influence over Americas European allies.

Russia is Europes main supplier of natural gas. Once Nord Stream 2 is operational, Gazprom would be able to sell additional gas to European customers without paying transit fees to Ukraine.

Championed by Ms. Merkel in 2015, a year after Russia first invaded Ukraine, Nord Stream 2 has long inflamed Washington and European capitals alike.

While Ms. Baerbock, the Green Party foreign minister, has not been shy about expressing her hostility toward the project, Ms. Merkel and Mr. Scholz have defended it on economic and energy security grounds and long ruled out using it as leverage in talks about sanctions.

It was only last week, standing next to the NATO general secretary, that the chancellor shifted his language, saying that everything would be on the table in case of a Russian invasion.

Putin gave NATO a new reason to exist, said Mr. Dirsus of the Institute for Security Policy in Kiel. Who knows, maybe he can teach the Germans once and for all that the world has changed and they need to be prepared to pay to defend peace.

Christopher F. Schuetze contributed reporting from Berlin and Andrew Higgins from Warsaw.

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Where Is Germany in the Ukraine Standoff? Its Allies Wonder. - The New York Times

KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the European Commission has approved KEYTRUDA, Mercks anti-PD-1 therapy, as monotherapy for the adjuvant treatment of adults with renal cell carcinoma (RCC) at increased risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. This approval is based on results from the Phase 3 KEYNOTE-564 trial, in which KEYTRUDA demonstrated a statistically significant improvement in disease-free survival (DFS), reducing the risk of disease recurrence or death by 32% (HR=0.68 [95% CI, 0.53-0.87]; p=0.0010) after a median follow-up of 23.9 months compared to placebo, in patients at increased risk of recurrence (defined in the clinical trial protocol as intermediate-high or high risk following nephrectomy and those with resected advanced disease).

KEYTRUDA addresses a critical unmet need for treatment options that help patients reduce their risk of cancer returning following surgery, said Dr. Thomas Powles, professor of Genitourinary Oncology and director of Barts Cancer Centre at St. Bartholomews Hospital. The European Commissions approval of KEYTRUDA brings certain patients with renal cell carcinoma a long-awaited therapy that has demonstrated a statistically significant reduction in the risk of disease recurrence or death by almost a third.

KEYTRUDA is the first adjuvant therapy approved for certain patients with renal cell carcinoma in Europe, providing the option of immunotherapy earlier in the course of their treatment, said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. This approval demonstrates our progress in bringing KEYTRUDA to patients with earlier stages of cancer, with the goal of helping more patients around the globe prevent disease recurrence.

This approval allows marketing of KEYTRUDA monotherapy in all 27 European Union member states plus Iceland, Lichtenstein, Norway and Northern Ireland.

Merck has a broad clinical development program exploring KEYTRUDA, as monotherapy or in combination, as well as several other investigational and approved medicines across multiple settings and stages of RCC, including adjuvant and advanced or metastatic disease.

Data Supporting the European Approval

The approval was based on data from KEYNOTE-564 (NCT03142334), a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial that enrolled 994 patients with increased risk of recurrence of RCC defined as intermediate-high or high risk, or M1 with no evidence of disease (NED). Patients must have undergone a partial or radical complete nephrectomy (and complete resection of solid, isolated, soft tissue metastatic lesion[s] in M1 NED participants) with negative surgical margins for at least four weeks prior to the time of screening. Patients with active autoimmune disease or a medical condition that required immunosuppression were excluded from the study. The primary efficacy outcome measure was investigator-assessed DFS. The secondary efficacy outcome measure was overall survival (OS). Patients with RCC with clear cell component were randomized (1:1) to receive KEYTRUDA 200 mg administered intravenously every three weeks (n=496) or placebo (n=498) for up to one year until disease recurrence or unacceptable toxicity.

At a pre-specified interim analysis with a median follow-up time of 23.9 months, KEYTRUDA demonstrated a statistically significant improvement in DFS, reducing the risk of disease recurrence or death by 32% (HR=0.68 [95% CI, 0.53-0.87]; p=0.0010) compared with placebo in patients with RCC at increased risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. Updated efficacy results with a median follow-up time of 29.7 months demonstrated KEYTRUDA reduced the risk of disease recurrence or death by 37% (HR=0.63 [95% CI, 0.50-0.80]; p<0.0001) compared with placebo. Median DFS has not been reached for either group. The trial will continue to assess OS as a secondary outcome measure.

The safety of KEYTRUDA as monotherapy has been evaluated in 7,148 patients with advanced melanoma, resected stage III melanoma (adjuvant therapy), non-small cell lung cancer, classical Hodgkin lymphoma, urothelial carcinoma, head and neck squamous cell carcinoma, colorectal cancer, endometrial, gastric, small intestine, biliary, pancreatic cancer or adjuvant therapy of RCC across four doses (2 mg/kg bodyweight [bw] every three weeks, 200 mg every three weeks, or 10 mg/kg bw every two or three weeks) in clinical studies. In this patient population, the most frequent adverse reactions with KEYTRUDA were fatigue (31%), diarrhea (22%) and nausea (21%). The majority of adverse reactions reported for KEYTRUDA monotherapy were of Grades 1 or 2 severity. The most serious adverse reactions were immune-related adverse reactions and severe infusion-related reactions. The incidences of immune-related adverse reactions were 36.1% for all Grades and 8.9% for Grades 3-5 for KEYTRUDA monotherapy in the adjuvant setting (n=1,480) and 24.2% for all Grades and 6.4% for Grades 3-5 in the metastatic setting (n=5,375). No new immune-related adverse reactions were identified in the adjuvant setting.

About Renal Cell Carcinoma

Renal cell carcinoma is by far the most common type of kidney cancer; about nine out of 10 kidney cancer diagnoses are RCCs. Renal cell carcinoma is about twice as common in men than in women. Most cases of RCC are discovered incidentally during imaging tests for other abdominal diseases. Worldwide, it is estimated there were more than 431,000 new cases of kidney cancer diagnosed and more than 179,000 deaths from the disease in 2020. In Europe, it is estimated there were more than 138,000 new cases of kidney cancer diagnosed and more than 54,000 deaths from the disease in 2020.

About Mercks Early-Stage Cancer Clinical Program

Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is studying KEYTRUDA in earlier disease states, with approximately 20 ongoing registrational studies across multiple types of cancer.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,700 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications in the U.S.

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [Tumor Proportion Score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.

KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or GEJ (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:

Cervical Cancer

KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).

KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.

Tumor Mutational Burden-High Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.

Triple-Negative Breast Cancer

KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.

KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test.

Selected Important Safety Information for KEYTRUDA

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the PD-1 or the PD-L1, blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of antiPD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5% (13) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients.

Hepatotoxicity and Immune-Mediated Hepatitis

KEYTRUDA as a Single Agent

KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients. Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients.

KEYTRUDA With Axitinib

First-line treatment of advanced RCC in combination therapy with axitinib (KEYNOTE-426)

KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT 3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT 3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT 3 ULN subsequently recovered from the event.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids were required in 77% (17/22) of patients; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.3% (8) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Hypophysitis

KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required in 94% (16/17) of patients; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in 0.1% (4) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Thyroid Disorders

KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in <0.1% (1) of patients.

Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. Hypothyroidism occurred in 8% (237/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. The majority of patients with hypothyroidism required long-term thyroid hormone replacement. The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC, occurring in 16% of patients receiving KEYTRUDA as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in 389 adult patients with cHL (17%) receiving KEYTRUDA as a single agent, including Grade 1 (6.2%) and Grade 2 (10.8%) hypothyroidism.

Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis

Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in <0.1% (1) and withholding of KEYTRUDA in <0.1% (1) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Immune-Mediated Nephritis With Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 89% (8/9) of patients. Nephritis led to permanent discontinuation of KEYTRUDA in 0.1% (3) and withholding in 0.1% (3) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Nephritis resolved in 56% of the 9 patients.

Immune-Mediated Dermatologic Adverse Reactions

KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with antiPD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received KEYTRUDA or were reported with the use of other antiPD-1/PD-L1 treatments. Severe or fatal cases have been reported for some of these adverse reactions. Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barr syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% of 2799 patients receiving KEYTRUDA. Monitor for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

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