Looking Forward: Experts Discuss Exciting Trends in 2012 Oncology Drug Pipeline

OncologyLive, January 2012, Volume 13, Issue 1

Pharmaceutical companies are investing billions of dollars and have more than 900 cancer medications in the pipelines.

Pharmaceutical companies are investing billions of dollars in a new age of oncology. The more than 900 cancer medications in the pipelines at drug companies and academic institutions constitute nearly 40% of all the drugs under development, according to industry analysts.

Such development efforts have brought several novel cancer treatments to market in recent months and promise several more advances in the coming months.

Which are the most exciting new medications and, more importantly, what specific trends will emerge this year to help bring effective, individualized treatment for more patients with cancer?

Here are thoughts from 6 oncologists at the forefront of drug research and testing at some of the nation’s most prestigious cancer treatment centers.

Kenneth C. Anderson, MD

Program Director and Chief

Division of Hematologic Neoplasias

Dana-Farber Cancer Institute

Kraft Family Professor of Medicine

Harvard Medical School

Boston, MA

Anderson expects good things from several new myeloma medications, including carfilzomib. The proteasome inhibitor, which appears to be active in relapsed multiple myeloma and seems very well tolerated by most patients, was accepted for FDA review in late November.

The researcher, however, is most excited by several general trends that may expedite drug testing and reduce failure rates.

Like everyone interviewed for this article, Anderson believes targeted medications, paired with diagnostic tests, will increasingly achieve both goals. Even when targeted medications fail in initial trials, he said, researchers understand them well enough to devise possible fixes rather than abandoning development.

A scientist at a Roche laboratory tests pharmacokinetic properties of drug candidates. Genentech, a member of the Roche Group, is developing new targeted oncology agents.

“Elotuzumab, when tried on its own, largely failed,” he noted, referring to a monoclonal antibody directed against the glycoprotein CS1 that is under investigation in myelomas. “In the past, that would have been the end of the story, but enough was known about the compound to predict that pairing it with lenalidomide would boost response, and trials of the combo have been outstanding.”

Anderson expects to see many drugs rescued from oblivion in similar fashion and to see a general trend toward more potent drug combinations. “Combination therapies have always been the norm, but we’re only just developing the tools to systematically optimize them,” he said. “These tools will allow us to better leverage every medication, old as well as new.”

Complementing these scientific advances, Anderson said, are major improvements in communications among pharmaceutical companies, academic researchers, government regulators, patient advocates, and other interested parties. These groups are working together better than ever to exchange thoughts and negotiate standards, leading several drugs to reach patients in record time and offering hope that many more will do likewise.

Edith A. Perez, MD

Deputy Director

Mayo Clinic Cancer Center

Serene M. and Frances C. Durling

Professor of Medicine

Mayo Medical School

Jacksonville, FL

Perez looks forward not only to pertuzumab, a targeted drug now under FDA review for previously untreated metastatic breast cancer, but also to seeing major improvements in traditional cytotoxic chemotherapies.

Pertuzumab attacks the same types of HER2- positive cancers as trastuzumab (Herceptin) but, according to Perez, it is anything but a me-too drug.

“A large study has shown that pertuzumab slows time to progression in patients receiving first-line therapy for HER2-positive advanced breast cancer,” said Perez, referring to the CLEOPATRA trial results released at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium. (Stories, pages 24-25)

She said pertuzumab, rather than working directly on the HER2 protein the way trastuzumab does, works at the joint dimer between HER2 and HER3, so the 2 drugs can be administered together.

Unlike some doctors who believe that traditional toxic chemotherapies are nearing the limits of their effectiveness, Perez expects the coming years to bring big improvement from the oldest types of cancer medications.

“We have been using chemotherapies for decades, but we still don’t know the basics about most of them, like what, exactly, they target. Ongoing research that may discover the specific targets of many agents could lead to diagnostic tests that would show who, exactly, would benefit from what types of chemotherapy,” Perez said.

Perez also has hopes for efforts designed to combine chemotherapies with chemical carriers. The carriers would protect healthy cells from the chemotherapy, and then dump the poisons directly on their targets. “Such a delivery mechanism would allow the use of much stronger chemicals, which would be far more likely to kill all the cancer,” she said.

Another trend that excites Perez is the move to conduct simultaneous clinical trials involving physicians and patients around the globe—a trend that will speed the drug development process.

Joanne Mortimer, MD

Vice Chair, Professor of Medicine

Department of Medical Oncology

Administrative Director

of Phase I Programs

City of Hope

Duarte, CA

Mortimer, who specializes in breast cancer, is excited about the potential for everolimus (Afinitor) for her patients. Results from the BOLERO-2 trial were among the highlights of the San Antonio Breast Cancer Symposium in December. (Read more >>> Exemestane Plus Everolimus New Standard of Care for Postmenopausal Hormone Receptor-Positive Advanced Breast Cancer)

Not only has the drug proved effective in combination with exemestane in women with advanced disease, it has resulted in something entirely unexpected: increased bone density.

“One of the most constant relationships in breast cancer is the inverse relationship between cancer risk and bone density. The estrogen that makes bones dense also seems to make cancer grow faster,” Mortimer said.

“It seemed universal, until we tested everolimus and found that it treated breast cancer and improved bone density,” Mortimer said. “There may be a real lead in there, and that’s exciting.”

Mortimer also is excited about the trend toward doing more biopsies on patients’ tumors, not just at initial diagnosis but also repeatedly throughout treatment.

The traditional assumption, she said, was that repeat biopsies wasted time because while tumors changed in size, their fundamental makeup remained the same. Recent studies, however, demonstrate that tumor composition changes with treatment.

“Imagine spraying Roundup on a patch of weeds. Most would die, but a few species would survive and move into the space once occupied by other weeds,” Mortimer said. “Many tumors are like that patch of weeds. They’re not any one thing but lots of different things.

“If you kill one subset of the tumor, the overall composition will change,” she said. “Take a HER2- positive cancer, treat it with Herceptin and you’ll often end up with a cancer that’s HER2-negative. Further treatment with Herceptin is a waste of money and dangerous to the patient. Routine biopsies let you see the changes and adjust treatment faster. I think they’ll be a big trend for just that reason.”

Gregory J. Riely, MD, PhD

Medical Oncologist

Memorial Sloan-Kettering Cancer Center

Assistant Professor of Medicine

Weill Cornell Medical College

New York, NY

Riely, who frequently designs and administers clinical trials targeting lung cancer and thymic tumors, sees great potential in crizotinib (Xalkori), an anaplastic lymphoma kinase (ALK) inhibitor he helped test.

“The really exciting thing with crizotinib is the speed with which it was developed and approved,” said Riely. “We didn’t even know this type of lung cancer existed until late 2007, which means it took about four years to find a drug that would attack it, test that drug, and get it approved. That is a triumph of science, of testing logistics, and of communication.”

Crizotinib is just one of the recent successes that lead Riely to believe both that drugmakers have created a repeatable process for developing targeted medications and that the FDA has learned to evaluate them efficiently.

“It’s possible that crizotinib and the others were low-hanging fruit, that we won’t be able to repeat the process again,” he said. “But I’m optimistic that we’ve developed tools for general application, not against every tumor type or even most tumor types, but against a fair number.”

Riely also believes that these new tools will, in the coming year and beyond, help physicians administer existing medications far more efficiently. For this reason, he lists erlotinib (Tarceva) among the drugs he is most excited about using in the coming year, even though the FDA first approved it in 2004.

Understanding drugs better is obviously a huge step. Ultimately, it means moving beyond the entire concept of first-line treatments and second-line treatments and just giving the right drug. ”

—Gregory J. Riely, MD, PhD

“Initially, we were using it in all patients with lung cancer, seeing strong responses in some and no responses in others, and having no idea why. Now we know that patients with EGFR mutations are the ones who get the most benefit,” said Riely, referring to the epidermal growth factor receptor gene.

“Understanding drugs better is obviously a huge step. Ultimately, it means moving beyond the entire concept of first-line treatments and second-line treatments and just giving the right drug,” he said.

Oncologic Drugs With 2012 FDA Action Dates*

Although years of laboratory exploration and clinical trial work precede the development of a new drug, the clock starts ticking once the FDA has agreed to accept a new drug application (NDA) or a biologics license application (BLA).

Milestones in the drug approval process include review by the Oncologic Drugs Advisory Committee (ODAC), whose recommendations the FDA typically accepts.

The Prescription Drug User Fee Act (PDUFA) date is the FDA's goal date for making a decision on whether or not to approve a drug.


Tumor Type



Key Dates

Axitinib (Inlyta)

Renal cell carcinoma

Tyrosine kinase inhibitor of VEGF 1, 2, and 3

Pfizer Inc

ODAC supports risk/benefit profile - 12/7/11

FDA grants approval - 1/27/12


Philadelphia chromosome-positive chronic myeloid leukemia

Small molecule inhibitor of Src and Abl kinases

Pfizer Inc

NDA filed — 1/27/12

PDUFA decision date not disclosed


Multiple myeloma

Proteasome inhibitor

Onyx Pharmaceuticals, Inc

PDUFA decision - 7/27/12

Decitabine (Dacogen)

Acute myelogenous leukemia

Injectable metabolic inhibitor

Eisai/ Astex Pharmaceuticals, Inc

ODAC review - 2/9/12

PDUFA - 3/6/12

Denosumab (Xgeva)

Reduce risk of bone metastastes in castrate-resistant prostate cancer

Monoclonal antibody;

RANK ligand inhibitor

PDUFA decision - 4/26/12

Mechlorethamine hydrochloride

Early-stage mycosis fungoides (T-cell lymphoma)

Gel formulation of chemotherapy agent

Ceptaris Therapeutics, Inc (formerly Yaupon)

NDA filed - 10/4/11

PDUFA decision date not disclosed


HER2-positive metastatic breast cancer

Monoclonal antibody


BLA submitted - 12/7/11

Pixantrone (Pixuvri)

Non-Hodgkin lymphoma


Cell Therapeutics, Inc

NDA voluntarily withdrawn - 1/30/12


Metastatic soft tissue or bone sarcomas

Small molecule mTOR inhibitor

Merck/ ARIAD Pharmaceuticals, Inc

NDA filed - 10/5/11

PDUFA decision - 6/5/12a

Vincristine sulfate (Marqibo)

Philadelphia chromosome-negative acute lymphoblastic leukemia

Nanoparticle-encapsulated alkaloid antimitotic

Talon Therapeutics

PDUFA decision - 5/13/12

Vismodegib (Erivedge)

Basal cell carcinoma

Small molecule Hedgehog inhibitor

Genentech/Curis, Inc

FDA grants approval - 1/30/12

aBased on standard review timeline.

VEGF denotes vascular endothelial growth factor; ODAC, Oncologic Drugs Advisory Committee; PDUFA, Prescription Drug User Fee Act; RANK, receptor activator nuclear factor kappa B; NDA, new drug application; BLA, biologics drug application; mTOR, mammalian target of rapamycin.

*This table is based on announcements by companies developing these therapies and may not include all pending action dates.

Richard Finn, MD

Co-Associate Director, Signal Transduction and Therapeutic Program Area, Jonsson Comprehensive Cancer Center, Assistant Professor, Department of Medicine, UCLA

Los Angeles, CA

Finn expects big things from many of the new targeted therapies aimed at a variety of tumor types, but he is particularly excited about drugs that may help underserved patients.

The liver cancer drug brivanib, for example, inhibits vascular endothelial growth factor and fibroblast growth factor receptors, and is effective for some patients whose disease has progressed on sorafenib (Nexavar). (Results of the phase III BRISK-PS trial, released after this interview, indicate the drug did not meet its primary endpoint of improving overall survival in hepatocellular carcinoma [HCC]. Nevertheless, Bristol-Myers Squibb said 3 additional phase III trials evaluating brivanib in different HCC populations are ongoing.)

“We’re developing drugs aimed at a lot of molecular targets, and there’s justifiable excitement, but we need to work even harder on newer, novel targets,” said Finn.

The need to find and attack more novel targets stems, Finn said, from the growing realization that cancer is fragmented into far more different diseases than even the experts ever realized. Many of those diseases have no treatment.

Looking forward, Finn said, this realization will change how drugs are tested. For example, a targeted lung cancer drug would not be tested in a generic lung cancer population because there is no generic lung cancer.

Even in cases where researchers stumble upon active compounds, they will seek to identify the specific population that is most likely to benefit before running large trials, which might otherwise fail, Finn said.

“Traditionally, in early trials, we monitored tumor sizes to see if the compound worked on some people rather than analyzing tumors to see who benefited and why,” Finn said.

“The growing trend is to biopsy the tumors from early trials to see who responds,” he said. “That will allow us to select the right subjects for later trials and to get the right drug to the right patients. These studies are the ones most likely to lead to getting an approved drug. They will help us make a targeted drug out of any drug.”

Carol Ann Huff, MD

Director, Myeloma Program

Assistant Professor, Oncology and Medicine, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Hospital

Baltimore, MD

Huff believes that pomalidomide offers real hope for patients with myeloma, not only because it may be more effective for some patients than its predecessors, thalidomide (Thalomid) and lenalidomide (Revlimid), but also because researchers are only beginning to understand how it works and which combinations are best. Celgene Corporation aims to seek FDA approval this year for the use of pomalidomide in relapsed multiple myeloma.

“It’s already impressive,” Huff said, “and we still don’t know the best ways to use it.”

Like everyone interviewed for this article, Huff cited the steady proliferation of targeted therapies as the top trend in cancer medicines, but she noted a gray lining in this otherwise silver cloud—the costs.

“The new targeted therapies have to cost more than the broad-range chemotherapies because they consume the same development costs but often work on fewer patients,” Huff said. “And the trend is only accelerating as the targets become more specific.”

The effectiveness of new medications also makes them more expensive. They extend life but rarely cure the underlying condition, so patients end up taking them for years rather than undergoing finite rounds of chemotherapy and radiation.

Another facet of the new medications that is both a major advantage and a major drawback is the fact that many of them are designed to be taken at home rather than administered in the office. Patients prefer taking medicine at home, but at-home treatments are generally covered by pharmacy benefits that, in the case of Medicare, have much higher copayments than the medical benefits that cover in-office treatment.

“I’ve had patients do the math and request to be treated in the office, even when the treatment wasn’t as good and threatened greater side effects, because they wanted to have something left to pass onto their families after they died,” Huff said. “I’m sorry to say it, but I think that’s a trend doctors will see more of.”

Oncology Drugs Given Fast Track Designations in 2011*

The FDA's Fast Track program is intended to expedite the review of drugs designed to fill unmet medical needs for patients with cancer and other serious diseases. Regulators communicate with drug developers earlier and more frequently under the program. These Fast Track designations were announced last year.





Key Dates

Radium-223 (Alpharadin)

Castrate-resistant prostate cancer in patients with bone metastases

Alpha particle-emitting nuclide

Bayer HealthCare Pharmaceuticals Inc



Locally advanced pancreatic carcinoma

Plasmid comprised of H19 gene regulatory sequences

BioCancell Therapeutics, Inc



Chemotherapy-induced neuropathic pain

Analgesic produced by Streptomyces alanosinicus

DARA BioSciences, Inc



Advanced prostate cancer

Androgen receptor signaling inhibitor

Medivation, Inc/ Astellas Pharma Inc



Metastatic and/or unresectable gastrointestinal stromal tumors

Oral inhibitor of angiogenic, stromal, and oncogenic receptor tyrosine kinases

Bayer HealthCare Pharmaceuticals Inc


*This table is based on announcements by companies developing these therapies and may not include all Fast Track designations from 2011.