Progress, Slow but Sure, Seen for Current Lung Cancer Therapies


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This year, we have some abstracts that help move things forward in lung cancer, maybe at a little bit slower pace than in previous years. But there are important points that we can learn from some of these abstracts,” commented Karen L. Reckamp, MD, of the City of Hope, who presented findings on improvements in current lung cancer therapy standards at the Best of ASCO San Diego meeting.

Key studies in the area of current therapy standards addressed combined-modality therapy, diagnostic tools for early-stage disease, and special considerations for therapy in patients with metastatic disease. “These are all things that are ultimately going to move the field forward in small baby steps,” she said.

Consolidation Chemotherapy in Locally Advanced NSCLC

A pooled analysis of 45 trials with a total of 3,447 patients assessed the benefit of consolidation chemotherapy after definitive concurrent chemoradiotherapy in patients with locally advanced non–small cell lung cancer (NSCLC).1 Median overall survival was 18.5 months with consolidation chemotherapy and 18.1 months without it. In an adjusted analysis, there was no significant survival benefit of consolidation chemotherapy. Findings were the same in subgroups stratified by time period, world region, and phase of trial.

“It doesn’t appear that consolidation adds a significant benefit to standard concurrent chemoradiation. But we still do it,” Dr. Reckamp noted, pointing to ongoing cooperative group trials. “And many people still believe we must do it. So there is some emotional rationale here that doesn’t necessarily fit with the data,” she added.

“The question is, will we follow the data; will we change our practice based on these studies? Or will we wait for the future trials and continue to believe based on our emotions that consolidation therapy is necessary?” she asked. “I think this is enough to say that outside of a clinical trial, consolidation should not be done.”

Delaying Thoracic Radiation in Limited SCLC

A randomized phase III noninferiority trial tested concurrent thoracic radiation therapy given with the first vs the third cycle of cisplatin and etoposide chemotherapy in 219 patients with limited-disease small cell lung cancer (SCLC).2 The complete response rate was 36% when thoracic radiation was given in the first cycle and 38% when it was delayed until the third cycle, meeting criteria for noninferiority. Progression-free survival and overall survival were statistically indistinguishable.

Patients given delayed thoracic radiation had a higher proportion of first failures that were locoregional only (51% vs 39%) but a lower rate of grade 3/4 febrile neutropenia (10% vs 22%).

“Radiation for limited-disease SCLC can be delayed until the third cycle of chemotherapy without changes in outcomes,” Dr. Reckamp commented, while adding that there may be some differences in locoregional control and toxicity.

“We need to base our decisions on the patients’ characteristics, the tumor, and the need for initiating therapy quickly vs being able to delay and wait for radiation planning,” she recommended.

FDG-PET to Diagnosis Stage I NSCLC

The American College of Surgeons Oncology Group (ACOSOG) Z4031 study assessed the accuracy of fluorodeoxyglucose positron-emission tomography (FDG-PET) for diagnosis of early lung cancer.3 Participants were 682 patients with a lung lesion clinically suspected to be stage I NSCLC. Final pathology showed cancer in 83%.

FDG-PET had a sensitivity of 82% and a specificity of 31% for identifying cancer, with an overall accuracy of 73%. The majority of false-positive were granulomas, and the majority of false-negatives were adenocarcinomas. The sensitivity of FDG-PET differed significantly across the eight enrolling study sites. The accuracy increased with lesion size (P < .001).

“We need to question our reliance on FDG-PET, especially in early-stage and stage I disease,” Dr. Reckamp commented, noting that the ordering of this test is “pervasive.”

“When you have somebody with a potential early-stage lung cancer and are asking is this lung cancer or not…, PET scan is still not as good as having a biopsy,” she maintained.

Combination Chemotherapy in Advanced NSCLC

A randomized phase III trial compared pemetrexed (Alimta) alone vs combined with carboplatin in 217 patients with stage IIIB/IV NSCLC and an ECOG performance status of 2.4 Patients in the combination therapy group tended to have higher rates of grade 3/4 anemia (12% vs 4%, P = .066) and grade 5 adverse events (4% vs 0%, P = .121). However, the combination therapy group still had better progression-free survival (5.9 vs 3.0 months, HR = 0.46, P < .001) and overall survival (9.1 vs 5.6 months, HR = 0.57, P = .001).

The subset of patients aged 70 years or older also derived survival benefit from the combination therapy vs the monotherapy (8.3 vs 6.1 months, HR = 0.49, P < .015).

“This definitely shows that in selected patients, we can use combination chemotherapy even in performance status 2 patients,” Dr. Reckamp said, noting that this is in fact a heterogeneous group.

“We need studies to investigate the best regimen and understand toxicities better,” she said, recommending that for now, regimens be based on comorbidities.

“Further trials are obviously needed to include these populations [performance status 2 patients and older adults] into our studies so that we can understand how best to treat [them], because clearly they are very underrepresented … and these are the majority of our patients,” she added.

Early Palliative Care Reduces Health-care Costs

A randomized trial conducted at the Massachusetts General Hospital Cancer Center assessed the effect of early palliative care on health-care costs in 151 patients with newly diagnosed metastatic NSCLC.5 Patients were assigned to early palliative care integrated with oncology care (meeting with a palliative care clinician within 3 weeks and at least monthly thereafter) or to standard care (meeting with a palliative care clinician only when requested by patient, family, or oncology clinician).

On average, total health-care cost per patient (for inpatient and outpatient visits, chemotherapy, and hospice services) in the final month of life was $2,282 less in the early palliative care group vs the standard care group. The biggest driver was the difference in cost for inpatient visits.

“We don’t know how well this will generalize to the general population and to populations outside of a large comprehensive cancer center with a very well established palliative care team,” Dr. Reckamp commented. Moreover, some end-of-life costs were not evaluated.

“Clearly, early palliative care integration is associated with better outcomes—improved quality of life, decreased chemotherapy—and this may also lead to decreased health-care costs at the end of life,” she said.

Ideally, oncology care and palliative care are envisioned as integrated and coexisting along a continuum, Dr. Reckamp noted. “I would argue with lung cancer that there is an accelerated course through this diagram, and often we end up near the end part of it even from the beginning. So symptom control and palliative care are incredibly important from the early stages because we are not talking about curative or even much life-prolonging treatment for most of our patients.” ■

Disclosure: Dr. Reckamp reported no potential conflicts of interest.

References

1. Yamamoto S, Tsujino K, Ando M, et al: Is consolidation chemotherapy after concurrent chemoradiotherapy beneficial for locally advanced non-small cell lung cancer? A pooled analysis of the literature. 2012 ASCO Annual Meeting. Abstract 7000. Presented June 4, 2012.

2. Park K, Sun J-M, Kim S-W, et al: Phase III trial of concurrent thoracic radiotherapy (TRT) with either the first cycle or the third cycle of cisplatin and etoposide chemotherapy to determine the optimal timing of TRT for limited-disease small cell lung cancer. 2012 ASCO Annual Meeting. Abstract 7004. Presented June 4, 2012.

3. Grogan EL, Deppen SA, Ballman KV, et al: Accuracy of FDG-PET to diagnose lung cancer in the ACOSOG Z4031 trial. 2012 ASCO Annual Meeting. Abstract 7008. Presented June 4, 2012.

4. Lilenbaum R, Zukin M, Pereira JR, et al: A randomized phase III trial of single-agent pemetrexed (P) versus carboplatin and pemetrexed (CP) in patients with advanced non-small cell lung cancer (NSCLC) and performance status (PS) of 2. 2012 ASCO Annual Meeting. Abstract 7506. Presented June 4, 2012.

5. Greer JA, McMahon PM, Tramontano A, et al: Effect of early palliative care on health care costs in patients with metastatic NSCLC. 2012 ASCO Annual Meeting. Abstract 6004. Presented June 2, 2012.


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