CFS&reg Experts: Novel Therapies and Onco-Genomics Add Heft to Precision Medicine

OncologyLive, Vol. 20/No. 19, Volume 20, Issue 19

Co-chairs William K. Oh, MD, Adam M. Brufsky, MD, PhD, and Benjamin P. Levy, MD, preview key topics that will be covered at the 37th Annual CFS®: Innovative Cancer Therapy for Tomorrow symposium.

Benjamin P. Levy, MD, considers himself a physician—scientist, a doctor who is devoted to his patients and balances this attention with clinical investigative work on biomarkers in immunotherapy and the value and potential of liquid biopsy. Investigation not only leads to discovery but also optimizes use of existing therapies and diagnostics, and therefore, it is important for fine-tuning the treatment that patients receive.

But the work of investigators and dedicated physicians must be distilled and made accessible so that oncologists and hematologists can make use of these advances. Further, physicians have a responsibility to familiarize themselves with improvements in care. “You’ve got to keep up,” said Levy, clinical director of medical oncology at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center at Sibley Memorial Hospital and a cochair of the 37th Annual CFS®: Innovative Cancer Therapy for Tomorrow symposium, which is to be held November 6 to 8 at the New York Marriott Marquis in New York, New York.

This year’s CFS® continues the tradition of delivering a compact program of interactive presentations on important and helpful developments in oncology across multiple tumor types. The agenda includes a robust emphasis on advances in immunotherapy and targeted therapy, biomarkers, and diagnostic tests. This is where much of the potential lies in putting the word precision into medicine.

The rapidly developing science of onco-genomics will be featured in “2019 Update From the Labs—Moving from Bench to Bedside,” a special segment of the program on Thursday, November 7. Panelists will discuss emerging analytical approaches involving clonal hematopoiesis, next-generation sequencing, and other areas.

Also weighing in with a top-level view of emerging trends in the oncology field will be Scott Gottlieb, MD, former FDA commissioner. He will deliver a keynote presentation and take questions from the audience during Thursday’s program.

The agenda for the annual gathering is crafted by the CFS® cochairs, each of whom brings an extensive and successful background in investigative and clinical work to the table in designing a meeting that will enable physicians to return to the clinic with the most advanced practical knowledge and the ability to raise their game immediately. In a series of interviews with OncologyLive®, the cochairs for this year’s meeting discussed their work, what they find most exciting about advances in the field, and how these developments have been incorporated into the CFS® program.

In addition to Levy, whose specialty is thoracic medicine and who is also an associate professor of oncology at The Johns Hopkins University School of Medicine, the cochairs are William K. Oh, MD, an expert in genitourinary (GU) malignancies, chief of the Division of Hematology and Medical Oncology at Mount Sinai Health System, and deputy director of The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai in New York, New York; and Adam M. Brufsky, MD, PhD, a breast cancer specialist who serves as associate chief of the Division of Hematology/Oncology in the Department of Medicine at the University of Pittsburgh School of Medicine in Pennsylvania. Brufsky is also medical director of the Magee-Women’s Cancer Program and associate director for clinical investigations at the University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center.

William K. Oh, MD

William K. Oh, MD

Mount Sinai

William K. Oh, MD, finds these 2 trends in GU cancers the most interesting: using targeted therapies sooner and the evolution of precision medicine, particularly in prostate cancer.

“The biggest trend in prostate cancer is really earlier use of targeted therapies,” said Oh. He describes precision medicine as “the calling card” of modern oncology.

An expert in the management of GU malignancies, including prostate, renal, bladder, and testicular cancers, Oh has research interests that extend to novel biomarkers and therapeutics in advanced prostate cancer, and he has served as principal investigator on numerous clinical trials in this disease type.

At CFS®, Oh will moderate the GU cancers program and deliver his own presentation on new randomized control trials in metastatic hormone-sensitive prostate cancer (mHSPC) and optimal therapy. The broader GU program will focus on the optimal timing and use of immunotherapies in bladder and renal cancer in relation to platinum-based chemotherapy and tyrosine kinase inhibitors, respectively.

Presenters will discuss sequencing strategies in the context of molecular changes, clinical factors, and the availability of new agents. “There are new targeted therapies, for example, in bladder and renal cancer, as well, which—just like in prostate cancer—will continue to break down what we used to think of as a single disease,” Oh said.

For example, some subsets of patients with bladder cancer may have FGFR mutations and be suited for FGFR inhibitors. In April, the FDA approved erdafitinib (Balversa) for patients with locally advanced or metastatic urothelial carcinoma with FGFR2/3 alterations, making it the first FGFR alteration—targeted therapy for the malignancy.1 In prostate cancer subsets, a PARP inhibitor may be appropriate. “We’re going to hear about how the average clinician can use some of this molecular data to make the best therapeutic choices for patients,” Oh said.

Local Treatment in Metastatic Prostate Cancer

One particularly interesting topic at the CFS® meeting will concern the use of local treatment such as surgery or radiation in metastatic prostate cancer, Oh said. This was addressed in the phase III STAMPEDE trial of men with newly diagnosed metastatic prostate cancer (N = 2061). Patients were randomized equally to standard of care (SOC; androgen deprivation therapy/docetaxel) or SOC with radiotherapy. Radiotherapy to the prostate improved overall survival (OS) by 32% in the 819 men with a low burden of metastatic disease (HR, 0.68; 95% CI, 0.52-0.90), which Oh defined as oligometastatic disease with fewer than 5 lesions. OS was not improved in the 1120 men with higher metastatic burden.2

Based on these findings, a change in SOC may be in progress, but the oncology community continues to debate the place of radiotherapy and surgery in patients with low-volume metastatic disease. The subject will be explored by the experts at CFS® in a Medical Crossfire® session, Oh noted: “We’re going to have a surgeon, a radiation oncologist, and a medical oncologist talk about whether we should do surgery, radiation, or nothing in these patients with oligometastatic disease."

With regard to moving therapies earlier in the lineup, androgen blockers are showing potential, Oh said. These agents are not generally thought of as targeted therapies but technically are, and they are being shifted to earlier disease states such as mHSPC and nonmetastatic castration resistant prostate cancer. “Many randomized trials are now suggesting that the benefit in those settings is more significant than if you wait until the patient develops metastatic castration-resistant disease,” he said.

However, newer agents will be the front-runners in prostate cancer treatment, he predicted: “I think the future is going to involve an understanding of the molecular alterations in cancer and incorporation of immunotherapy, for which we are behind in prostate cancer.” An understanding of driver mutations and improvements in patient selection for treatment will be key to this process.

The value for patients is that newer agents hold potential for improved survival with lower toxicity, which Oh said is important because physicians sometimes need to overcome their hesitancy to work on a patient’s cancer. “I’ve been in this field for over 20 years now, and when I started, there was a tremendous amount of skepticism about treating patients with prostate cancer. I would often hear from doctors and patients that they were ‘old’ or that they were ‘too frail’ to get any therapy,” he said.

It is partly true that men with advanced prostate cancer were not well served by the drugs available 2 decades ago, but that has changed, Oh said: “We have a host of new treatments that have definitely kept patients alive longer— there’s no question about it.”

Chemotherapy Adds Value to Hormone Therapy in Prostate Cancer

Oh mentioned the phase III ENZAMET trial, which was discussed in the plenary session at the 2019 American Society of Clinical Oncology Annual Meeting. ENZAMET explored the use of the nonsteroidal, next-generation androgen-targeted drug enzalutamide (Xtandi) compared with standard nonsteroidal antiandrogen (NSAA) therapy. After 3 years, patients (N = 1125) randomized to enzalutamide plus SOC achieved an 80% OS rate compared with 72% for patients assigned to NSAA plus SOC.3

These findings not only contributed to a priority review designation for enzalutamide as a treatment for mHSPC but also suggested an answer to the question regarding the usefulness of chemotherapy plus androgen receptor-targeted therapy for these patients, Oh said.

Docetaxel in combination with enzalutamide was given to a portion of patients in ENZAMET and led to a lower 3-year OS (74% vs 83%) than for those who did not receive docetaxel. Conversely, docetaxel plus NSAA was superior to NSAA (75% vs 70%).4 “Most of the benefit in ENZAMET was in the group of patients who did not receive chemotherapy, suggesting, perhaps, that there’s some cross benefit between chemotherapy and androgen-receptor targeting therapies, such that you can use either but not necessarily get benefit from doing both. That’s why it was a plenary session talk,” Oh said.

Treating patients earlier in nonmetastatic (or M0) castration-resistant disease with next-generation androgen targeted therapies is a perplexing issue, Oh said. In this tumor type, 3 drugs have been approved based on metastatic-free survival (MFS): enzalutamide, apalutamide (Erleada), and darolutamide (Nubeqa). MFS may be a less compelling endpoint to some because it’s not the same as OS.

“It really suggests that if you use one of these next-generation androgen targeted therapies, you can delay metastasis by up to 2 years,” Oh said. Delaying development of a metastatic lesion can help avert pain and bone fracture, but there’s a trade-off, he said: “The flip side is that you have to take these drugs every day, and they have negative adverse events, including hot flashes, fatigue, and osteoporosis, so they’re not without their own risks.” They’re also costly, he noted.

Prostate specific antigen (PSA) doubling time of ≤10 months has been used as a cutoff for predicting benefit from these agents, but the real math may be less precise, according to Oh. “What we don’t know is: What if your PSA is doubling once a year instead of in 10 months or less? What if it’s a little bit slower? What if you’re a little older? Would you still benef it from these drugs? We really don’t know the answer to that,” he said. Conversely, patients with a rapid doubling time may find they’re intolerant to these drugs. A patient’s choices for therapy may be quite limited in that setting, he said: “These are some of the things we’re going to have to sort through over the next few years to optimize the use of these new drugs and get the most benefit with the least harm.”

Recent findings in metastatic castration-resistant prostate cancer (mCRPC) demonstrate the value of a molecular precision medicine approach. For example, data from the phase II TOPARP-B trial of PARP inhibitor olaparib (Lynparza) in mCRPC provide evidence that this agent could be an exciting game changer, Oh said. Investigators noted higher responses for patients with BRCA1/BRCA2 mutations (83.3%) or PALB2 mutations (57.1%). “This is important, because, remarkably, up to 20% of men with metastatic CRPC may have either a germline or somatic mutation in a DNA repair pathway, mostly BRCA2, and that’s much higher than we used to think it was,” Oh said. “If you have a DNA damage repair mutation, you may benefit from a PARP inhibitor or possibly platinum-based chemotherapy, so that’s an example of how precision oncology is working its way into prostate cancer. It’s really exciting, and I think it will change the way we sort patients.”5

In the theater of immunotherapy and prostate cancer, questions remain that Oh would like to see answered. Microsatellite instability (MSI)—high tumors respond to checkpoint inhibitors, but the incidence of MSI is low in prostate cancer—no more than 1% to 2% of cases, according to Oh. Even so, about 10% of patients with mCRPC respond to checkpoint inhibitors, and the reason needs to be determined. There are likely molecular drivers of response that go beyond current clinical biomarkers such as tumor mutational burden, PD-L1 staining, and MSI status, Oh said.

Additionally, the value of other agents in combination with checkpoint inhibitors needs to be clarified. “There are many trials looking at vaccines or IL-2 derivatives, such as NKTR214, or combinations with ipilimumab [Yervoy] and nivolumab [Opdivo]. Once workable combinations are identified and patient classification improves, immunotherapy undoubtedly will move earlier in the treatment regimen,” Oh said. “Why wait until the patients get metastatic CRPC before we start these?”

Oh said he thrives on these developments because, ultimately, his job is to get the best outcomes for his patients. “The bottom line for me is that interaction in the examination room: me facing a patient and his family and saying, ‘This is what I can do to help you live your life as long as possible with the best quality of life possible.’ That’s why we physicians went into this field of oncology.”

Adam M. Brufsky, MD, PhD

Adam M. Brufsky, MD, PhD

University of Pittsburgh Medical Center Hillman Cancer Center

As a cochair of the CFS® meeting, Adam M. Brufsky, MD, PhD, brings a strong record in clinical investigation to the conference’s stable of discussions. He participated in trials of bisphosphonates whose results demonstrated the value of these agents in bone loss prevention as well as in inhibiting tumor growth in the bone microenvironment. In the early 2000s, he was involved in the development of the docetaxel, carboplatin, and trastuzumab (TCH) neoadjuvant regimen in HER2-positive breast cancer. Both endeavors led to changes in standards of care.

Brufsky’s current interests extend to the role of immunotherapies and targeted therapies in early-stage breast cancer settings, upcoming trials of AKT inhibitors in triple-negative breast cancer (TNBC), improvement of PD-1/PD-L1 staining and staining interpretation, and an understanding of the relative predictive and prognostic values of genomic assays in early-stage breast cancer. Advances in these cutting-edge topics will be covered in detail at CFS® this year.

One of the overarching themes of the CFS® conference will be the role of immunotherapy and targeted therapies in earlier-stage settings across tumor types. In the field of breast cancer, Brufsky takes special interest in recent findings from the KEYNOTE-522 trial (NCT03036488), in which the combination of the anti—PD-1 antibody pembrolizumab (Keytruda) and chemotherapy demonstrated improved pathologic complete response (pCR) in the neoadjuvant or presurgical treatment of patients with TNBC.

Merck was scheduled to provide results of this trial at this year’s European Society for Medical Oncology conference in Barcelona, Spain; these findings will also be discussed in detail at CFS®. Brufsky said that a new standard of care may be at hand if the findings confirm an improved pCR rate in women receiving immunotherapy as part of their systemic therapy in the neoadjuvant setting.

“I think it’s really interesting what we’re going to be doing with triple-negative breast cancer,” Brufsky said. The trial results may help shed light on the proper timing of immunotherapy in TNBC, who should be eligible, and how patients should be screened, he added.

In March, the FDA approved the first immune checkpoint immunotherapy for breast cancer, granting an indication for the anti—PD-L1 antibody atezolizumab (Tecentriq) in combination with nab-paclitaxel (Abraxane) for patients with PD-L1–positive unresectable locally advanced or metastatic TNBC.6

New Targeted Agents

Upcoming trials of agents that target AKT mutations in TNBC are also of interest and will be previewed at the CFS® forum, Brufsky said. In this setting, ipatasertib has shown promise in recent trials. In data presented earlier this year, ipatasertib in combination with atezolizumab and chemotherapy or nab-paclitaxel as a first-line option for patients with advanced TNBC demonstrated an overall response rate of 73% irrespective of tumor biomarker status.7 In findings from the phase II LOTUS study, reported in June 2018, frontline treatment with ipatasertib in combination with paclitaxel for locally advanced or metastatic TNBC demonstrated a median OS of 23.1 months versus 18.4 months in patients treated with placebo plus paclitaxel.8

PI3K inhibitors are also on tap for discussion, Brufsky noted. In May 2019, the FDA approved alpelisib (Piqray) in combination with the endocrine therapy fulvestrant for the treatment of postmenopausal women and men with hormone receptor—positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer following progression on an endocrine-based regimen. Alpelisib was “the first PI3K inhibitor to demonstrate a clinically meaningful benefit in treating patients with this type of breast cancer,” the FDA noted. In tandem, the FDA approved a companion diagnostic test for detection of PIK3CA mutations in tissue or liquid biopsies.9

Brufsky is currently investigating the use of diagnostics to further personalize care. His presentation at CFS® will center on the use of Oncotype DX, EndoPredict, and MammaPrint in node-positive, early-stage breast cancer. Myriad data already exist on the use of these tests in node-negative, early-stage breast cancer, and they are helpful in predicting who needs chemotherapy and who does not, but investigators do not know as much about the usefulness of these tests in node-positive cancer. “It’s really node-positive where I think that we need to figure out whether these tests are as good at predicting who needs chemotherapy,” he said.

This theme will extend to a Medical Crossfire® debate scheduled for the CFS® program in the breast cancer program, Brufsky noted. “There are subsets of women with early-stage breast cancer who come in with bulky disease in their breast, and normally we give them neoadjuvant therapy, and normally it’s neoadjuvant chemotherapy, and I think the question is ‘Are there patients we can give neoadjuvant hormonal therapy to?’ This is getting at the theme of using the biology of the cancer to be more precise in what we do.” Moving in the direction of neoadjuvant hormonal therapy would be a “sea change,” he said.

Neoadjuvant Endocrine Therapy in Breast Cancer

Advantages to endocrine therapy exist, particularly in its ability to shrink the tumor and conserve breast tissue. But in the neoadjuvant setting, it remains underused in part because patients and physicians often want the confidence that comes with a stronger form of therapy. In some cases, trying hormonal therapy is important.

Brufsky cited a patient who came to his office recently with a 4- to 5-cm breast tumor, strongly estrogen receptor and progesterone receptor positive, with heavy lymph node involvement. “It’s very slow growing, and if she wants, we probably would do some sort of breast conservation or attempted breast conservation, and we’re thinking very strongly of giving her an LHRH [luteinizing hormone-releasing hormone] agonist and an aromatase inhibitor. Even though we’d love her to respond to chemotherapy, it’s likely that she won’t,” he said. At CFS®, a panel of surgeons and medical oncologists will discuss the case, and Brufsky expects a lively exchange.

With a host of new agents approved in recent years, clinicians have opportunities to do more to improve quality of life for patients, Brufsky said. “I think we’re really starting to turn a lot of metastatic breast cancer into a more chronic disease—where people have survivals now of 5 years, 10 years—and what we’re trying to do now is maximize their benefit and minimize the toxicity in a lot of new therapies.”

In HER2-positive breast cancer, antibody—drug conjugates (ADCs) are leading the charge, including as replacements for chemotherapy in some settings. Ado-trastuzumab emtansine (T-DM1; Kadcyla) is approved for patients with recurrent metastatic HER2-positive breast cancer who have received prior treatment and after prior neoadjuvant therapy with trastuzumab and a taxane. New ADCs in development include trastuzumab deruxtecan (DS-8201) for progressive HER2-positive disease and sacituzumab govitecan (IMMU-132) for TNBC. “These are agents that people could be on for a while,” Brufsky said. “They don’t have as much toxicity as some of the standard systemic chemotherapy agents.”

Brufsky is also interested in the unfolding discussion on interpretation of PD-1/ PD-L1 immunostaining in breast cancer. Immunohistochemistry is used for patient selection, but it remains an imprecise method for predicting patient response. “You really want to appropriately apply the therapies for the people who will respond to the best treatment, and we’re working on that,” he said.

This topic will be covered at CFS®. The debate concerns many aspects of staining for accurate interpretation of PD-1/L1 expression; choosing samples for staining, across tumor types, is not yet an exact science. “There are certain organs, it turns out, that really don’t have a lot of immune infiltrate in their metastasis, such as [the] liver [and] breast. It’s a lot more complicated than just taking a biopsy from any metastatic site and staining it and assuming it’s going to be the same.”

In the field of breast cancer, Brufsky has been a prolific investigator who considers himself fortunate to have played a part in clinical studies that changed standards of care. A dozen years ago, he was involved in confirmatory trials that demonstrated how up-front use of the bisphosphonate zoledronic acid could help prevent bone loss associated with the use of aromatase inhibitors in premenopausal women with early-stage breast cancer receiving letrozole.10

His research into the use of bisphosphonates further examined the role these agents could play in the bone microenvironment as inhibitors of tumor growth. Brufsky and his fellow investigators theorized that osteoclastic activity could be reduced through use of bisphosphonates, leading to improved survival.

Their landmark meta-analysis, published in 2015, noted that bisphosphonates versus control (open label or placebo) in the postmenopausal group demonstrated significant reductions for bone-recurrent cancer (10-year risk, 6.6% vs 8.8%; rate ratio [RR] = 0.72, 0.60-0.86; 2-sided P = .0002) and for breast cancer mortality (10-year risk, 14.7% vs 18.0%; RR = 0.82, 0.730.93; 2-sided P = .002), independent of the type of bisphosphonate used.11 This led to their conclusion that widespread adoption of bisphosphonates should be a standard of care for the adjuvant treatment of early-stage breast cancer in postmenopausal women.12

“I published the first paper in 2007 showing the potential survival benefit for these agents, and then in the meta-analysis, we realized it was probably true,” Brufsky said.13 Zoledronic acid was initiated with adjuvant letrozole in postmenopausal women with early-stage breast cancer, and in the control arm, patients received zoledronic acid only when bone loss became clinically significant or a fracture occurred. The follow-up analysis showed that fewer patients receiving up-front zoledronic acid experienced disease recurrence than patients in the delayed group: 7 (0.84%) versus 17 (1.9%) (P = .0401).10

Brufsky also takes pride in having played a leading role in the development of the TCH neoadjuvant regimen, which later evolved in to TCHP with the addition of pertuzumab (Perjeta), in HER2-positive breast cancer. Brufsky’s role in the early 2000s focused on the use of TCH in metastatic disease, but “it turned out to become the standard of care for early-stage, HER2-positive breast cancer for systemic therapy,” he said. TCH, he added, became the nonanthracycline control agent in the landmark BCIRG 006 trial, whose results confirmed the long-term efficacy of trastuzumab in patients with HER2-positive, node-positive, or high-risk node-negative earlystage breast cancer while also validating the theory that anthracyclines increase toxicity and may not contribute to better outcomes. No statistical advantage was seen in terms of disease-free survival and OS in the anthracycline-based experimental arm versus TCH.14

Oncology holds increasing potential for patients with cancer to live high-quality lives, but patient—doctor discussions should address the limitations of modern medicine, Brufsky said. Physicians should offer hospice as an option for patients for whom treatment potential may have been exhausted, yet a discussion about end-of-life care has a rightful place much earlier in the treatment process.

“Maybe not as soon as someone [receives a breast cancer diagnosis] because people are going to live on average 4 or 5 or 6 years, if not longer, nowadays,” but patients must clearly understand that they can say enough is enough. Equally important, physicians should recognize that patients often look to them to say this. “You don’t say that to everybody, but there’s always an art to that,” Brufsky said.

Benjamin P. Levy, MD

Benjamin P. Levy, MD

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Benjamin P. Levy, MD, was initially drawn to oncology because he thought that his primary interest would be the clinical care of patients, but he soon discovered that he had an aptitude and a passion for clinical investigation and research—and this has strengthened his commitment to being an oncologist and enriched his work. “That bond that you have with patients is so sacred and so important. That is what initially drew me into this field. But over the years, I’ve learned that what has truly kept me engaged is the science, which is rapidly evolving,” said Levy.

Levy is now a specialist in both targeted and immunotherapeutic approaches for the treatment of advanced-stage lung cancer. His work includes investigating the utility of biomarkers in both tissue and plasma that may predict efficacy or lack thereof to novel therapies. As a cochair of the CFS® meeting, Levy has applied this expertise to the development of a robust program on lung cancer that includes an emphasis on molecular markers for patient selection and the emerging clinical utility of liquid biopsies in advanced non—small cell lung cancer (NSCLC).

“We’ve really tried to highlight the particular genotypes that are important, given the new drugs that are making their way to the clinical space,” Levy said. This is an essential area for accuracy in selecting patients for therapy, and meeting participants will discuss many developments in onco-genomics. “The common thread is personalized medicine. There is a growing list of genotypes that we’ve identified as relevant and, more important, that we’ve discovered new therapies for.” Immunotherapy makes up the second core subject area at the conference, and presenters and panelists will cover immunotherapy options for advanced- and early-stage disease.

Role of Liquid Biopsies in Lung Cancer

Levy’s knowledge and interest in circulating free DNA (cfDNA) blood tests for cancer will come to the forefront in his moderation of a Medical Crossfire® panel discussion at CFS® titled “When Should We Be Using Liquid Biopsy?” Levy believes strongly that cfDNA testing has a significant role to play as a prognostic and diagnostic tool in lung cancer, specifically in patients with advanced NSCLC.

These tests enable physicians to understand the genetic underpinnings of lung cancer but also hold potential for long-term monitoring of patients’ progress on therapeutic regimens, Levy said. “This latter application is not yet approved, but it’s something that we’re investigating. We’re looking at longitudinal assessments of the cfDNA within the plasma to help better understand how patients are doing on therapy. This is what I call real-time monitoring of patients.”

During the Medical Crossfire® panel talk, Levy hopes to address the debate over whether every patient with advanced NSCLC should have a liquid biopsy in conjunction with a tissue biopsy. “I think that will be one of the highlights of the discussion,” he said. Panelists will also address the potential for observing patients on targeted therapy with cfDNA over time.

A third aspect of the discussion will focus on the use of cfDNA tests to monitor patients with lung cancer for minimal residual disease following curative intent therapy with either surgery and/or chemotherapy with radiation “to see whether we can detect recurrences in the plasma earlier than we can on a computed tomography scan.”

Although liquid biopsies have met with skepticism in the past, the mounting evidence in support of their ability to provide a picture of tumor activity is contributing to a sense of excitement over what might be achievable with these tests in the future, Levy said. “To me, it’s a fascinating story to be able to genotype your patients and do this in a rapid way with liquid. Patients sometimes don’t need another biopsy; they just need the liquid biopsy. I think the sky’s the limit.”

Many of the presentations in the lung cancer section of the CFS® program will center on molecular markers and testing for these. With knowledge of biomarker significance expanding, individual, single/sequential biomarker tests are becoming outdated, Levy said. “I think every patient should have comprehensive next-generation genomic profiling so that we can get a better understanding of the drivers of disease. Most testing these days should include a larger panel—at least a 50-gene panel, if not more. I think the days of testing for just a handful of mutations are over.” Clinicians can do this by blood biopsy or tissue test, he added.

Interestingly, Levy noted, genomic testing can predict both for efficacy and lack of efficacy with immunotherapy. This was demonstrated by findings from a recent study presented at the International Association for the Study of Lung Cancer’s 2019 World Conference on Lung Cancer.

STK11/LKB1 genomic alterations led to shorter progression-free survival (PFS) versus STK11/LKB1 wild-type tumors in patients with PD-L1—positive, nonsquamous non–small cell lung cancer treated with pembrolizumab, pemetrexed, and carboplatin or cisplatin (PCP). PFS was 4.8 versus 6.9 months, respectively.15

Among patients with the same disease type treated with pemetrexed and carboplatin/ cisplatin (PC), those with STK11 mutations also had shorter PFS compared with STK11 wild type: 3.7 versus 5.6 months. In the same study, investigators found that KEAP1 alterations versus KEAP1 wild type were also associated hear Gottlieb, the former FDA commissioner, discuss the fast-changing oncology scene in a much-anticipated keynote address, Levy noted. “Gottlieb is an outside-the-box thinker who brought real change to the FDA. He will give us a high-level overview of where we’re heading in the field of oncology.”

Levy looks forward to chairing a CFS® session on cardio-oncology and the importance of heart-related issues for patients with cancer. “This is something that I will learn a lot from, so I very much look forward to the input from those experts.”

The CFS® meeting will cover a lot of ground, and oncologists and hematologists will find it a valuable boost in their efforts to keep up with practice and investigative developments. “I think it’s important to stay current given the rapid pace of drug discovery and shifting treatment paradigms. It’s also important to collaborate, and that has a lot of meanings. That means reaching out to colleagues to ask questions and engaging other physician—scientists.” The CFS® meeting, Levy said, makes all this possible.

References

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