Events

Videos

Podcasts

Articles

IASLC World Conference on Lung Cancer

Treatment with first-line avelumab yielded promising clinical benefit and durable antitumor activity in patients with advanced non—small cell lung cancer (NSCLC), according to a presentation at the IASLC 17th World Conference on Lung Cancer.

After a median follow-up of 13 weeks, the objective response rate with the anti-PD-L1 immunotherapy agent was 22.4% (95% CI, 16.2-29.8) and the median progression-free survival (PFS) was 17.6 weeks (95% CI, 11.6-23.6) among 156 patients who participated in one of the NSCLC cohorts of the wide-ranging JAVELIN Solid Tumor trial,

 Claire Verschraegen, MD, director, The University of Vermont Cancer Center, said in describing early analysis data at the conference in Vienna.

JAVELIN Solid Tumor is an ongoing, multicenter phase I study that is exploring avelumab in multiple solid tumor types. The agent is a fully human IgG1 monoclonal antibody that blocks the PD-1/PD-L1 interaction but leaves PD-L2 signaling intact, thereby allowing antibody-dependent cellular cytotoxicity to contribute to antitumor activity.

“This is the largest phase I trial ever conducted, with approximately 1700 patients across 16 cohorts,” Verschraegen remarked.

In the first-line NSCLC cohort, the primary objective was to evaluate the best overall response of first-line avelumab at 10 mg/kg administered intravenously over 1 hour every 2 weeks until progression, unacceptable toxicity, or study withdrawal in patients with histologically confirmed stage IV or recurrent NSCLC.

The patients were unselected for expression PD-L1 levels, did not have an activating 

 mutation or ALK-positive tumors, and had not received previous systemic treatment for metastatic or recurrent disease.

The median patient age was 70 years (range, 41-90 years), ECOG performance score was 0 (29.5%), 1 (69.2%), or 3 (1.3%), and tumor histology was adenocarcinoma (66%) or squamous (28.8%) in most patients. The median time from diagnosis of metastatic disease was 1.5 months (range, 0.2-92.0 months).

Although patients were not selected by PD-L1 expression levels for admission into this trial, immunohistochemistry analysis revealed that just over half (56.4%) of patients were positive for PD-L1 expression using a ≥1% staining cutoff.

The best overall response by RECIST v1.1 was complete response in 2 (1.3%) patients, partial responses in 33 (21.1%) patients, and stable disease in 67 (42.9%) patients. Progressive disease was experience by 40 participants (25.6%), and 14 (9%) patients could not be evaluated.

Tumor shrinkage was observed in 64.3% of patients, and this shrinkage was 30% or greater in 28.6% of patients.

Overall, the median treatment duration was 20 weeks (range, 2 to 46 weeks), and 64 (41.0%) patients remained on avelumab treatment. The 24-week PFS rate was 37.2% (95% CI, 28.6-45.7).

Similar to other immunotherapeutic agents, the time to response was rapid; 28 of 35 responding (80%) patients demonstrated a response by the first or second assessment and as early as 12 weeks. At data cut-off, 68.6% of responding patients maintained response.

Potential immune-mediated any-grade TRAEs were observed in 16 (10.3%) patients; of these, just 1 (0.6%) case of adrenal insufficiency was grade 3. No grade 3 or higher pneumonitis was seen. No treatment-related deaths occurred on study, and 11 (7.1%) patients discontinued treatment due to a TRAE.

Serving as discussant for the study, Edward B. Garon MD, said that avelumab would more than likely not expand the group of patients who could benefit from PD-1/PD-L1 inhibition. “These data support the idea that avelumab could be equivalent to the current standard treatment, but not better,” said Garon, medical director of Thoracic Oncology at David Geffen School of Medicine at UCLA, Santa Monica.

The authors noted that the PD-L1 expression analysis is ongoing, as is a phase III trial of avelumab versus platinum-containing doublet chemotherapy as first-line treatment of patients with PD-L1—positive advanced NSCLC.3

Meanwhile, avelumab is advancing in other tumor types; Verschraegen noted the recently updated results from a phase II trial of avelumab in patients with Merkel cell carcinoma (MCC).4 The FDA granted avelumab a breakthrough therapy designation as a treatment for patients with metastatic MCC following progression after at least 1 prior chemotherapy regimen.

Merck KGaA, based in Darmstadt, Germany, is sponsoring the NSCLC development of avelumab along with its US biopharmaceutical division, EMD Serono.

Jerusalem G, Chen FL, Spigel D, et al. JAVELIN Solid Tumor: Safety and Clinical Activity of Avelumab (Anti-PD-L1) as First-Line Treatment in Patients with Advanced NSCLC. Presented at: 17th World Lung Cancer Conference, the Annual Meeting of the International Association for the Study of Lung Cancer (IASLC); December 4-7, 2016; Vienna, Austria.

NIH Clinical Trial Registry. www,ClinicalTrials.gov. Identifier: NCT01772004.

NIH Clinical Trial Registry. www,ClinicalTrials.gov. Identifier: NCT02576574.

Kaufman HL, Russell J, Hamid O, et al. Avelumab in patients with chemotherapy refractory metastatic Merkel cell carcinoma: a multicenter, single-group-, open-label, phase 2 trial. 

. 2016;17(10):1374-1385. http://dx.doi.org/10.1016/S1470-2045(16)30364-3.

View more from the IASLC 17th World Conference on Lung Cancer

Treatment-related adverse events (TRAEs) of any grade occurred in 103 (66%) patients with avelumab; the most common adverse events occurring in ≥5% of patients were infusion-related reaction (IRR) in 28 (17.9%) patients, and fatigue, which was reported in 27 (17.3%) patients. Grade ≥3 TRAEs consisting of IRRs and fatigue occurred in 5 patients (3.2%) patients and 4 (2.6%) patients, respectively.

Treatment with first-line avelumab yielded promising clinical benefit and durable antitumor activity in patients with advanced non–small cell lung cancer.

Early Results Positive for First-Line Avelumab in NSCLC

Joshua Roth, PhD, assistant member, Fred Hutchinson Cancer Research Center, discusses the rationale behind the development of a novel risk-prediction algorithm in the context of screening patients for lung cancer. He discussed this during an interview at the IASLC 17th World Conference on Lung Cancer in Vienna, Austria.

Low-dose computed tomography (LDCT) lung cancer screening has been shown to increase detection of cases at an early stage and reduce lung cancer mortality, in comparison with X-ray or no screening at all. However, the benefits associated with such screening are reduced in patients who are considered to be poor candidates for curative intent surgery in the event of screen-detected, early-stage disease.

The rationale, says Roth, is to encourage shared decision-making between physicians and patients when the latter must undergo screening for lung cancer. The conversation should cover both potential benefits and harms associated with screening, such as false positives, or the adverse side effects of radiation. The main benefit lies in possible early detection of a tumor, according to Roth, which is then followed by early intervention with either surgery or radiation therapy.

Dr. Roth on the Rationale Behind a Novel Risk-Prediction Model in Lung Cancer Screening

Javier Zulueta, MD, head of the Pneumology Department, co-director, Lung Cancer Area, Clinica Universidad de Navarra, discusses the LuCED test, a non-invasive tool used to detect early stage lung cancer, during an interview at the IASLC 17th World Conference on Lung Cancer in Vienna, Austria.

Low-dose computed tomography (LDCT) screening for lung cancer often leads to follow-up scans for indeterminate nodules. The non-invasive LuCED test may resolve nodule findings and reduce LDCT false positives. When using this test, patient sputum is analyzed by the Cell-CT, which computes 3D images of single cells, allowing measurement of 3D structural biomarkers to identify potentially abnormal cells.

According to Zulueta's findings, the LuCED test demonstrates accurate detection of early stage lung cancer with the potential of detecting pre-cancerous conditions of the lung. These results suggest that suspicious nodules may be efficiently reconciled by this novel tool when used with LDCT.

Dr. Zulueta on the Non-Invasive LuCED Test for Detection of Early Stage Lung Cancer

While treatment with nivolumab (Opdivo) significantly improved overall survival (OS) over docetaxel in patients with advanced non—small cell lung cancer (NSCLC) in the CheckMate-057 trial, an analysis of deaths occurring within 3 months of initiation of therapy showed numerically more deaths in the nivolumab arm, according to findings presented at the IASLC 17th World Conference on Lung Cancer in Vienna.

The absolute difference in death events between arms within the first 3 months was 15.

“Although nivolumab significantly improved overall survival versus docetaxel in patients with previously treated advanced nonsquamous NSCLC in the CheckMate-057 trial, the Kaplan−Meier overall survival curves for nivolumab and docetaxel crossed at approximately 7 months, suggesting non-proportional hazards between arms,” said Solange Peters, MD, PhD, head of the Thoracic Malignancies Program in the Department of Oncology at the University of Lausanne in Switzerland.

This led Peters and colleagues to investigate the relationship between patient baseline disease characteristics—including PD-L1 expression&mdash;and death within the first 3 months of treatment in a post-hoc analysis of data from 582 patients participating in CheckMate-057. All patients had nonsquamous NSCLC and experienced progressive disease (PD) during or after platinum-based doublet chemotherapy; 292 patients were randomly assigned to receive intravenous nivolumab at 3 mg/kg every 2 weeks, and 290 patients were assigned to intravenous docetaxel at 75 mg/m2 every 3 weeks. Nivolumab patients were allowed to continue this treatment beyond PD.

CheckMate-057 met the primary endpoint of OS; median OS was 12.2 months with nivolumab versus 9.5 months in the docetaxel arm (HR, 0.75; 95% CI, 0.83-0.91).

 The 1-year OS rate was 51% versus 39% with nivolumab versus docetaxel, respectively, and the 2-year OS rate continued to favor nivolumab.

However, a numerically higher risk of death was observed with nivolumab compared with docetaxel, with 59 deaths occurring in nivolumab-treated patients versus 44 deaths in the docetaxel arm. At 3 months, 80% of nivolumab-treated patients versus 85% of docetaxel-treated patients were alive, although after this time-point among patients alive longer than 3 months, OS favored nivolumab over docetaxel (HR, 0.59; 95% CI, 0.47−0.74).

The investigators observed that these early deaths were not treatment-related and were attributed to disease progression. Therefore, they evaluated the association between baseline characteristics and early death. Patients were stratified according to prior therapies received, location of disease sites, smoking status, ECOG performance status (PS), PD-L1 expression and the presence of 

No single baseline factor reliably characterized the OS subgroups. However, by multivariate analysis, factors evaluated in concert were found to associate with higher risk of death during the first 3 months with nivolumab versus docetaxel. The analysis revealed that nivolumab-treated patients with a poorer prognosis (ECOG PS 1, and/or progressive disease) at baseline combined with having lower or no PD-L1 expression may be at higher risk of death within the first 3 months of treatment.

“However, the majority of nivolumab-treated patients with these factors were alive and did not die within the first 3 months, and experienced substantial subsequent benefit,” Peters commented.

She described baseline PD-L1 expression as “a continuum, ranging from 1% to 100%, with increasing expression associated with enhanced overall response and OS benefit from nivolumab; this continuum had no effect on response rates in docetaxel-treated patients.”

“Nivolumab is the standard of care as second-line treatment for advance squamous and nonsquamous NSCLC. While enhanced clinical activity with nivolumab correlates with increasing tumor PD-L1 expression, patients with low or no PD-L1 expression have a comparable probability of response,” she added.

Peters also noted that deep and durable nivolumab responses were observed with nivolumab irrespective of PD-L1 expression levels in the tumor. The favorable safety profile demonstrated with nivolumab was also irrespective of PD-L1 status.

A landmark 3-month evaluation of OS by PD-L1 status in patients alive at 3 months showed that median OS in patients with PD-L1 expression <1% was 14.7 months with nivolumab versus 11.4 months with docetaxel (HR, 0.66; 95 % CI, 0.45-0.97), whereas median OS in patients with PD-L1 expression ≥1% was 17.4 versus 11.3 months with nivolumab versus docetaxel (HR, 0.59; 95 % CI, 0.47-0.74).

“PD-L1 status alone is not considered an appropriate biomarker for nivolumab treatment selection in pretreated advanced NSCLC, but rather should be considered in the context of other patient/disease characteristics,” Peters advised. “Additional biomarker research is ongoing to help identify patients with advanced NSCLC who may derive the most clinical benefit from nivolumab.”

Peters S, Cappuzzo F, Horn L, et al. Analysis of early survival in patients with advanced non-squamous NSCLC treated with nivolumab vs docetaxel in CheckMate 057. Presented at: IASLC 17th World Conference on Lung Cancer; Vienna, Austria; December 4-7, 2016. Abstract OA03.05.

Borghaei H, Paz-Ares L, Horn, L. Nivolumab versus docetaxel in advanced nonsquamous non—small-cell lung cancer. 

While treatment with nivolumab (Opdivo) significantly improved overall survival over docetaxel in patients with advanced non–small cell lung cancer in the CheckMate-057 trial, an analysis of deaths occurring within 3 months of initiation of therapy showed numerically more deaths in the nivolumab arm.

Prognostic Factors Plus PD-L1 Expression May Be Linked With Early Survival Risk for Nivolumab in NSCLC

Tobacco cessation is imperative for patients’ health, especially in the context of lung cancer screening programs. According to Douglas Arenberg, MD, the importance of this matter often falls under oncologists’ radars.

“Oncologists should know that it’s never too late to stop smoking,” says Arenberg, an associate professor in the Department of Internal Medicine at the University of Michigan.

At the University of Michigan, Arenberg and colleagues initiated a formal lung cancer screening study in 2013. The researchers audited selected clinic visits at random to assess adherence to published tobacco cessation guidelines. Those findings then prompted them to initiate a systematic, multi-step program to improve upon tobacco practices, from assessing tobacco use to prescribing pharmacotherapy, and referral to tobacco cessation counselors.

: Please provide an overview of the study you presented here at the meeting.

 during the IASLC 17th World Conference on Lung Cancer, held in Vienna, Austria, Arenberg, discusses the preliminary findings of this study, and the critical importance of maintaining quality tobacco cessation practices in healthcare clinics.

: This is more of a quality-improvement initiative than it is a research study, which is a bit of a departure from my day-to-day work. It started kind of innocently a few years ago, when I had a research resident that wanted to do a research project. We sat and talked about what she was interested in, and we came up with an idea where she was going to look at what our university health system providers did in terms of the basics of tobacco cessation. We defined what we thought the basics were, which we defined based on something put together by the US Preventive Services Task Force.

They recommend the 5 A’s, which stand for the following: ask every patient about tobacco smoking; advise every smoker to quit; assess the willingness to quit; offer assistance to quit either in terms of motivational interviewing or pharmacotherapy; and then arrange a follow-up. Within the limits of our ability to tell how well we were doing those 5 things in a retrospective review of patient charts, we combined that with a survey of physicians at the University of Michigan. I wouldn’t say it was a well-designed or thorough survey, but it was as good as we could do at the time, simply asking people how well they thought they did, and then comparing that with what we found from reviewing the charts. Not surprisingly, what we found was that we, as physicians, think we do a better job than we actually do.

It was on that background that I came into contact with some people from the Michigan Department of Health, and they asked us to set up a system-wide change in terms of how we approach tobacco cessation. The University of Michigan Health System is distributed over a state that’s 3 times the size of Austria, and we have 150 outpatient centers, 40 clinics, 3 hospitals, and nearly 2 million outpatient visits per year.

It’s a daunting task to try and change all of that in 1 fell swoop. How do you eat an elephant? You take one bite at a time. This quality-improvement project is basically our first or second bite of the elephant, which is to simply start by planting these ideas in the minds of various key leaders in each of these clinical centers that are affiliated with the university.

We provided them with some training, and we took 1 individual from each clinic. As an enticement, we provided them with training through the University of Massachusetts Tobacco Treatment Specialist Training Program that we put on in Ann Arbor. We sent them back to the clinics and said, “Take this expertise, and use it any way you want, but here are the things that were important to us.” We then got monthly reports back on how they did regarding the 5 A’s: ask, advise, assess, assist, arrange.

One of the easiest ways to change behavior is to measure it. Over the last year, we’ve shown people their performance and the performance of other clinics. If they wanted to make changes, we came to their clinics and gave 5 or 10 minute talks at their staff meetings, but the most important thing we did was simply tell them that this was something we felt was important.

What are the major takeaways from your study?

Everyone recognizes the importance of tobacco cessation, but trying to squeeze that into the context of primary care, where doctors are trying to take care of patients with diabetes, high blood pressure, heart disease, high cholesterol, etc. We were trying to put this into a context that was both easy and convenient for them to carry out—kind of the bare-minimum basics. We felt that was one of the biggest challenges, just to get this on people’s radars.

The initial results of our study have shown that there was, in the first month, a dramatic increase in some of the more relevant measures. All of our measures about tobacco cessation are made remotely by using a reporting system through our electronic health records. We are really using surrogate measures of the actual outcomes, and that’s, from a research perspective, probably one of the biggest weaknesses here.

We’re not really measuring tobacco cessation at the individual level, and we’re not even really measuring individual provider behavior. We’re looking at population-based data.

However, within the context of a very low-budget process, we have made some progress in terms of raising the importance of tobacco cessation on the radar of our providers, and making it easier for them by having expertise available in the clinic—somebody they can grab and say, “Hey, what do you think about this patient or this medication?” A few minutes of motivational interviewing for a patient on site is at least as effective as a one-time phone call from a centralized system, which we previously used for providing tobacco cessation advice.

Prior to this project, our tobacco treatment specialists were all located in a very centralized location, in one obscure, hard-to-find building in Ann Arbor, Michigan. When you’re trying to provide service to a statewide distribution of patients and providers, we thought that was a recipe for failure, so what we’re really trying to do is de-centralize the expertise and put best practices on everybody’s radars.

With that, we have made some progress, though we still have a long way to go. We have learned that there is still a lot more of the elephant there to take bites of, but there are more strategic ways to increase this important aspect of provider primary care.

We have tried to establish a monthly rotation of appearing in these clinics with our reports. Each of these clinics operates differently. We have learned a few things from some of the more successful clinics in terms of what they did that worked, and we take that practice and bring it to other clinics and say, “You may want to try this really simple solution.”

We’re not there to judge their performance. There are so many masters, if you will, in this quality improvement environment that we work in. People are measuring things, and you’re constantly being assessed by payers, supervisors, patients, and what we really want people to know is that we’re not there as part of that judgmental process. We’re there to make their jobs easier.

We’ve learned about some really simple interventions. In one clinic, for example, every patient who was a smoker was handed a real simple piece of paper asking, of course, about their smoking history, but specific questions asked, “Are you ready to quit?” and “Do you want to meet with a tobacco cessation specialist?”

And just that simple piece of paper, the second the physician walks in the room, they know that patient is anxious to quit, and that creates an opportunity in that 5- or 10-minute clinic visit for an intervention that can be pretty effective. This is just simple advice from a physician, which we often forget to do in the context of a busy primary care clinic. Simple advice from a physician goes a long way towards motivating quit attempts. Of course, we want to back that up with follow-up phone calls, and/or with providers’ prescriptions of pharmacotherapy.

What would you like the community oncologist to ultimately take away from these findings?

We’re trying to take all these best practices and assemble it into a Frankenstein, if you will, of effective, low-cost practices. I look at this as an opportunity to create long-term relationships. Think of a wheel with its spokes. At the center of the wheel is the tobacco treatment specialist program in Ann Arbor, which is full of some very highly qualified, highly motivated individuals. The spokes are these various clinics distributed throughout Michigan. That simple relationship will pay dividends in the long run. The hard part is measuring success, and we have to believe we’re going to be successful, because we’re only measuring surrogates right now.

Oncologists should know—and this is part of the mission of the IASLC Tobacco Control and Smoking Cessation Committee, to make this widely known&mdash;that it’s never too late to stop smoking. There isn’t a patient out there, either with or without cancer, who can’t benefit in some way from tobacco cessation. Even patients who are undergoing the palliative care phase of their cancer journey can benefit from tobacco cessation.

These are people who are on oxygen and they’re at danger if they’re smoking, but even quality of life can be improved in the short-term with tobacco cessation. However, it has to be done right; it has to be done with compassion, not judgment. Despite all of the wonderful things that my colleagues in oncology do, they lose sight of the fact that it’s never too late to stop smoking, and engaging their patients with tobacco cessation experts is in both theirs and their patients’ best interests.

Douglas Arenberg, MD, discusses preliminary findings of a screening study, and the critical importance of maintaining quality tobacco cessation practices in healthcare clinics.

IASLC World Conference on Lung Cancer | Conference

Early Results Positive for First-Line Avelumab in NSCLC

Dr. Roth on the Rationale Behind a Novel Risk-Prediction Model in Lung Cancer Screening

Dr. Zulueta on the Non-Invasive LuCED Test for Detection of Early Stage Lung Cancer

Prognostic Factors Plus PD-L1 Expression May Be Linked With Early Survival Risk for Nivolumab in NSCLC

Expert Highlights Importance of Novel Findings With Tobacco Cessation Practices