Mike Hennessy, Sr, Chairman

Delivering the right treatment to the right patient with an eye toward tumor characteristics and gene alterations is at the heart of precision medicine. In this issue, we explore ongoing efforts to achieve precision medicine across disease settings.

The advent of immune checkpoint inhibitors (ICIs) across many cancer settings has been nothing short of remarkable, and none more so than in esophageal cancer—as detailed in the Special Report. Because of a paucity of effective treatments, results from the KEYNOTE-590 (NCT03189719) and Check-Mate 649 (NCT02872116) trials evaluating the combination of ICIs and chemotherapy in the frontline setting have given renewed hope to clinicians who treat patients with esophageal cancer (pages 26-29). In the second-line setting and beyond, findings from the KEYNOTE-181 (NCT02564263) and ATTRACTION-3 (NCT02569242) trials further established ICIs as a viable treatment in patients who are refractory or intolerant to previous chemotherapy in advanced disease.

This issue’s hepatocellular carcinoma coverage focuses on efforts to refine the use of lenvatinib (Lenvima) in this difficult-to-treat cancer. Although the agent has demonstrated antitumor effects in the second line, long-term safety data are still lacking with adverse effects that require monitoring by the treating clinician (page 47). Patients enrolled in clinical trials are different from populations treated in the real world, so efforts to delineate adverse effects are always welcome and useful to community oncologists in the clinic. In the second study presented at the American Association for the Study of Liver Diseases Annual Meeting, the use of relative dose intensity and levels of ammonia were identified as potential predictors of tolerability for lenvatinib (page 51).

The small molecule inhibitor PT2385 was evaluated in patients with von Hippel–Lindau (VHL) disease–associated clear cell renal cell carcinoma (ccRCC) and nonrenal tumors in a presentation during the Society of Urologic Oncology (SUO) Annual Meeting (pages 36-37). Disease stabilization and improvement were observed for all patients with VHL manifestations. In another study presented during the SUO meeting, nivolumab (Opdivo) given in the neoadjuvant setting demonstrated tolerability in patients with nonmetastatic, high-risk ccRCC (pages 44-45).

In the Precision Medicine in Oncology column, we turn to the NCI-MATCH trial (pages 54-55). In this umbrella trial, investigators from the ECOG-ACRIN Cancer Research Group and the National Cancer Institute sought to determine whether therapy could be better targeted if oncologists could identify molecular alterations using next-generation sequencing and administering currently available approved or experimental drugs—either singly or in combination—that fit those targets.

We look forward to sharing these advancements in precision medicine in future issues of 

Articles

Despite Limited Treatments, Advances in Frontline HCC and High-Risk RCC Heralded

In March 2020, the United States was in the early stages of the coronavirus disease 2019 (COVID-19) pandemic. We shut down the entire country and ground the economy to a halt to slow the spread of the virus. Think back to March and how much uncertainty we were living under.

Nine months later, the FDA approved 2 COVID-19 vaccines under emergency authorization. Before New Year’s Day, millions of Americans had received the vaccine, including frontline physicians and health care providers and nursing home patients, our most vulnerable citizens.

Nine months. Take a moment to let that sink in. 

The mainstream media has crafted a narrative about the COVID-19 pandemic that’s almost entirely negative. For the purpose of ratings, they have described the US response to the pandemic as blundering from 1 mistake to the next. This narrative is false. 

There is another way—a more accurate and under appreciated way—to tell the story of the past 9 months. It is a story of heroism, innovation, and precise science, performed under unbelievable pressure. 

Let’s not mince words: The US and the world must appreciate the role of the pharmaceutical industry—the investigators, physicians and business leaders—who are rescuing the world from COVID-19. It’s the medical breakthrough of our lifetime. Instead of dwelling on why many in the media are ignoring this, let’s review some facts.

Since the discovery of COVID-19, here is what scientists have accomplished: They identified a novel virus; unlocked and sequenced its genetic code; created new therapies to save lives; and developed multiple safe and effective vaccines using messenger RNA technology, a technology hopefully applicable to future vaccine development, especially in cancer. Margaret Liu, MD, a biomedical scientist and member of the MJH Life Sciences™ COVID Coalition, called it a breakthrough for mRNA vaccines.

The United States has 2 vaccines approved for emergency use, 1 from Pfizer/BioNTech and another from Moderna, and the AstraZeneca/Oxford vaccine has been approved for emergency use in the UK. In addition, there are 64 vaccines undergoing clinical trials at the moment, including 20 in phase 3 trials. In the US and throughout the world, the pharmaceutical industry has answered the call and invested heavily in this effort.


This was the fastest vaccine development program in history, and it’s not even close. David Pride, MD, PhD, a microbiologist at the University of California, San Diego, estimates that vaccines typically take 10 to 15 years to develop. Until the COVID-19 pandemic, the fastest development timeline was 4 years, for the mumps vaccine.

Many government systems moved quickly to lessen the burden of onerous regulations and provide funding so that vaccines could be developed quickly but with rigorous standards. Perhaps it should be a lesson to all of us that regulation and innovation can be calibrated more effectively during “normal” times as industry races to develop new therapies for other chronic conditions—cancer, diabetes, heart disease, and more.

The next step of the process—distribution of the vaccine—will be as challenging as the development phase, if not more so. But again, the pharmaceutical industry is rising to the occasion. Factories worldwide are working overdrive to produce hundreds of millions of vaccine doses.

 Less than a month after the Pfizer vaccine was approved, more than 15.4 million doses of vaccine have been distributed throughout the country, and more than 4.6 million individuals have received their first dose, according to data from the Centers for Disease Control and Prevention (CDC). Many patients are already receiving their second dose. 

Although 15.4 million doses are impressive, some expected 20 million doses. But that is moving the goal line, as 6 months ago many observers didn’t think a vaccine would be available until 2021.

Members of our COVID Coalition told us that the holidays slowed the rollout considerably. Nancy Messonnier, MD, a physician with the National Center for Immunization and Respiratory Diseases at the CDC, expects a rapid increase in administered vaccines during the first few days of 2021. 

Every day, more people will be vaccinated. After health care workers and our most vulnerable citizens, other frontline workers will be next. Teachers will be vaccinated so our children can return to school. And soon, all Americans will be able to receive the vaccine at their doctor’s office or at a CVS or Walgreens.

Remember, we accomplished this in 9 months, with the help, dedication, and expertise of our pharmaceutical industry heroes. Next time you turn on the TV and see negativity, turn it off and imagine instead where we will be in 9 months.



This was the fastest vaccine development program in history, and it’s not even close. David Pride, MD, PhD, a microbiologist at the University of California, San Diego, estimates that vaccines typically take 10 to 15 years to develop. Until the COVID-19 pandemic, the fastest development timeline was 4 years, for the mumps vaccine.

How Pharmaceutical Innovation Is Saving the World 

As I write this, the 2016 ASCO conference has just concluded in Chicago. And, as is typical with this event, the amount and level of groundbreaking research and information presented at this year&rsquo;s conference is nothing less than staggering in its scope, innovation, and promise.

This level of discovery could not be achieved without regular, incisive reviews of current research to give us perspective on where we have been and where we are headed in the development of bold, new targeted therapies for a wide variety of tumor types.

The Journal of Targeted Therapies in Cancer

deliver this research in the form of peer-reviewed articles from leading oncology thought leaders.

This issue&rsquo;s peer-reviewed article section includes &ldquo;Targeted Therapy for Advanced Squamous Cell Lung Cancer,&rdquo; which looks at squamous cell, an aggressive subset of lung cancer that presents therapeutic challenges, as it is genetically distinct from adenocarcinoma, with higher incidence of complex mutations. The authors discuss the evaluation of targeted therapies in squamous cell lung cancer, focusing on the rapid development of promising targets and drugs.

&ldquo;Immune Checkpoint Blockade: A New Strategy for the Treatment of Breast Cancer&rdquo; reviews the expanding role of immunotherapy as a breast cancer therapeutic. While breast cancer has traditionally not been viewed as immunogenic, recent clinical trials of immune checkpoint inhibitors in metastatic breast cancer have shown promising anti-tumor activity, and studies are underway to help define the role of immune-targeting drugs in the treatment of this tumor type. The authors describe the immune environment of breast cancer and summarize recently reported clinical trial results of immune checkpoint inhibitors in breast cancer.

In &ldquo;Efficacy and Safety of High-Dose Interleukin-2 Treatment in Melanoma Patients with a History of Brain Metastases,&rdquo; the authors evaluate high dose interleukin-2 (IL-2) therapy, which has had infrequent but durable responses in metastatic melanoma (MM), but has been controversial when used in patients with brain metastases (BM) due to safety concerns and limited data on efficacy in this population. This study evaluates tumor response rates and toxicity profiles of IL-2 therapy in a more contemporary cohort of patients with MM and a history of BM.

This issue&rsquo;s clinical research article section presents a variety of pieces on genitourinary cancers, looking at the effectiveness of abiraterone in metastatic castration-resistant prostate cancer, the validity of US Preventive Services Task Force recommendations for prostate-specific antigen testing, an observational study of low-risk prostate cancer patients enrolled in active surveillance, the effectiveness of combination therapy on bone pain and quality of life in metastatic castration-resistant prostate cancer, and the findings of a study on treatment of patients with early prostate cancer with unilateral high-intensity focused ultrasound.

We hope you enjoy the many relevant, fascinating articles in this issue along with updates on the latest targeted treatment news.

As I write this, the 2016 ASCO conference has just concluded in Chicago. And, as is typical with this event, the amount and level of groundbreaking research and information presented at this year&#39;s conference is nothing less than staggering in its scope, innovation, and promise.

Mike Hennessy, Sr, Chairman | Authors

Articles

Despite Limited Treatments, Advances in Frontline HCC and High-Risk RCC Heralded

How Pharmaceutical Innovation Is Saving the World

From the Chairman: Moving Forward With Bold Innovation