Stage IV NSCLC That Worsens during Chemo Could Be Treated with Erlotinib and SBRT

The gist: Stage IV non-small cell lung cancer (NSCLC) patients whose cancer worsened during platinum-based chemotherapy might benefit from treatment with the drug erlotinib and stereotactic body radiation (SBRT) therapy.

“Treatment with stereotactic body radiation therapy and erlotinib appeared highly effective in patients with metastatic stage IV non–small cell lung cancer who progressed on prior platinum-based chemotherapy, according to results of a single-arm phase 2 study.

“Patients with stage IV NSCLC who progress on first-line chemotherapy historically demonstrate poor survival outcomes, and they typically fail in original sites of gross disease, according to background information provided by researchers.

“Puneeth Iyengar, MD, PhD, assistant professor of radiation oncology at UT Southwestern Medical Center, and colleagues hypothesized that stereotactic body radiation therapy (SBRT) may help systemic agents delay relapse.

“Iyengar and colleagues evaluated PFS, OS and other outcomes among 24 patients (median age, 67 years) who underwent second- or later-line treatment with SBRT plus erlotinib (Tarceva; Genentech, Astellas).”

SBRT/Erlotinib Yield Big Improvements in Stage IV NSCLC

The gist: Stage IV non-small cell lung cancer (NSCLC) patients who receive stereotactic body radiation therapy (SBRT) along with the drug erlotinib may experience a longer amount of time before their cancer worsens. That was the conclusion of a recent clinical trial with 24 volunteer patients. In the trial, patients went for 14.7 months without their cancer worsening, compared to the historical rate of 2 to 4 months.

“A small trial yielded ‘dramatic’ results with high progression-free and overall survival using stereotactic body radiation therapy (SBRT) along with erlotinib for patients with stage IV non–small-cell lung cancer (NSCLC).

“ ‘Historically, drug therapy has failed to durably control gross visible tumors in most patients,’ said Robert Timmerman, MD, of the UT Southwestern Medical Center in Dallas, in an email. ‘In our new treatment paradigm, the SBRT, not the drugs, controls gross disease. Instead the drug is used to avoid the appearance of new tumors that would have otherwise progressed from microscopically hidden tumor.’

“The new trial was a single-arm, phase II study including 24 patients with a median age of 67 years. All patients had progressed through platinum-based chemotherapy, and the median follow-up was 11.6 months. Results were published online ahead of print on October 27 in the Journal of Clinical Oncology. After erlotinib treatment began for each patient, SBRT was delivered to all disease sites.

“The median progression-free survival was 14.7 months, and the median overall survival was 20.4 months. Though this trial had no comparator arm, these are substantially longer than historical studies of NSCLC patients who receive systemic therapy; typically progression-free survival and overall survival are 2 to 4 months and 6 to 9 months, respectively…

“ ‘The experience is exciting because the intervention seems to have dramatically changed the onset and pattern of failure,’ Timmerman said. ‘Our 14.7 month progression-free survival means that patients had an extended ‘holiday’ from progression during which they could get on with their lives and stop having to focus on finding yet another treatment.’ “

Interstitial Lung Disease is Significant Risk Factor for Lung Inflammation

The gist: New research shows that doctors should be mindful when prescribing stereotactic body radiation therapy (SBRT) to early-stage non-small cell lung cancer (NSCLC) patients who have a condition known as interstitial lung disease (ILD). Doctors sometimes prescribe SBRT for these patients because standard tumor-removal surgery may not be a good option for them. However, new research shows that giving SBRT to NSCLC patients with ILD may put them at greater risk for a life-threatening condition called radiation pneumonitis. The researchers say that doctors should therefore carefully consider the severity of ILD and the risk of radiation radiation pneumonitis when prescribing SBRT to a patient.

“ILD is a group of diseases that cause scarring and stiffing of the tissue and space around the air sacs in the lungs, which results in diminished gas exchange. The incidence of ILD among lung cancer patients is higher than in the general population as tobacco smoking is a common risk factor for both. Some lung cancer patients with ILD may not be considered good candidates for surgical therapy. SBRT uses sophisticated techniques to deliver a targeted and focused radiation dose to a tumor in order to stop the growth locally with limited damage to surrounding healthy tissue. SBRT is considered an acceptable therapy choice for early-stage NSCLC patients who are not good candidates for or decline surgery.

“In order to determine the optimal treatment for early-stage lung cancer patients with ILD, researchers at Kyoto University in Japan examined the incidence of radiation pneumonitis and the clinical outcomes in 157 patients who underwent SBRT alone for stage I NSCLC…

” ‘Our results suggest that the impact of ILD on radiation pneumonitis depends on the preexisting severity of the ILD findings and clinicians should be cautious when considering SBRT for those with significant ILD findings,’ say the authors. ‘However, other than radiation pneumonitis, life-threatening complications after SBRT are rare. Thus, if the severity of ILD and the risk of radiation pneumonitis are carefully evaluated, SBRT is a curative-intent treatment option for those with early-stage NSCLC and pretreatment ILD.’ “

10 Years of Data Reveals Excellent, Sustained Local Control With Minimal Side Effects for Medically Inoperable, Early Stage Lung Cancer Patients

The gist: Recent research shows good results for a treatment called stereotactic body radiotherapy (SBRT) for early stage lung cancer patients whose tumors cannot be removed by surgery. The research looked at the 10-year medical records of 300 patients treated with SBRT. 79% of their tumors had “excellent long-term, local control.”

“Analysis of data from an institutional patient registry on stereotactic body radiotherapy (SBRT) indicates excellent long-term, local control, 79 percent of tumors, for medically inoperable, early stage lung cancer patients treated with SBRT from 2003 to 2012, according to research presented today at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology. The Symposium is sponsored by the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), the International Association for the Study of Lung Cancer (IASLC) and The University of Chicago Medicine.

“The 300 patients in the study had 340 lesions (tumors) and were treated from October 1, 2003 through December 31, 2012, at the Cleveland Clinic, one of the early adopters of SBRT technology for lung cancer patients in the United States. Patients in the study had a median age of 74 years (range = 37-97 years), a median Karnofsky Performance Status (KPS) of 80 (range = 40-100), and were not candidates for surgery because of associated medical conditions, of which chronic obstructive pulmonary disease (COPD) was the most common (62 percent). Median follow-up was 17.4 months (range = 0.3-112.2 months), with 46.7 percent (140) patients alive at the time of follow-up. Median tumor diameter was 2.4 cm (range 0.1-10 cm), and 36.3 percent of tumors (123) had either no biopsy or a non-diagnostic biopsy. Fifteen percent of patients (45) received two or more SBRT treatments…

” ‘We have been privileged in demonstrating that lung SBRT can now be considered the standard of care for medically inoperable patients with early stage lung cancer,’ said Gregory M.M. Videtic, MD, lead study author, and a radiation oncologist at the Cleveland Clinic Foundation and associate professor of radiation oncology at the Cleveland Clinic Lerner College of Medicine, Case Western Reserve University. ‘Since our results indicate no unusual long term side effects, we are hoping to extend the potential uses of this therapy to more-fit, operable lung cancer patients whose cancer has not spread outside of the lung and to collaborate with other institutions on conducting such a clinical trial. SBRT could provide a more minimally invasive procedure than surgery, with fewer side effects and improved patient outcomes.’ “

SBRT Transforms Lives of Many With NSCLC (CME/CE)

The gist: People with early-stage, non-small cell lung cancer that can’t be removed by surgery may benefit from treatment with stereotactic body radiation therapy (SBRT). That was the conclusion of a recent clinical trial—a research study with volunteer patients. All patients in the trial could not have their tumors surgically removed because of medical conditions like emphysema or heart disease. Five years after SBRT, 40% of the patients were still alive. Cancer returned (recurred) in only 7% of the patients after five years. The researchers say this result is on par with surgery.

“A series of patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) had a 5-year survival of 40% following treatment with stereotactic body radiation therapy (SBRT), results of a cooperative-group trial showed.

“A fourth of the 59 patients remained alive and disease free after a median follow-up of 48 months. The rate of locoregional failure accelerated after 3 years, primarily in untreated areas.

“The frequency of severe toxicity changed little between 3 and 5 years, Robert Timmerman, MD, of the University of Texas Southwestern Medical Center in Dallas, reported here at the American Society for Radiation Oncology meeting.

” ‘The irradiated tumors are very well controlled, with a 5-year primary tumor recurrence rate of only 7%,’ Timmerman said during an ASTRO press briefing. ‘This is on par with surgery. Survival continues to decline as you might expect from a very frail population with competing causes of death, but still very impressive at 5 years at 40%. The median survival is 48 months and 7 years among surviving patients.’ “

For Some Lung Cancer Patients, Surgery May Yield Better Long-Term Results

“Patients with early stage non-small cell lung cancer (NSCLC) who are otherwise healthy fare better over time if they undergo conventional surgery versus less-invasive radiosurgery to remove their cancer, according to a Yale study. The findings are scheduled to be presented at the 56th annual conference of the American Society for Radiation Oncology in San Francisco.

“The study used Medicare billing records of 1,078 lung cancer patients age 67 and older from across the United States to assess shorter- and longer-term complications and outcomes related to surgery versus radiosurgery (also known as stereotactic body radiotherapy, or SBRT). The patients were treated in academic and private practice settings of all sizes.

“While the findings generally support current practices of treating healthier NSCLC patients with surgery rather than radiosurgery, researchers were surprised by how much better surgical patients fared long-term, said the study’s first author, James B. Yu, M.D., assistant professor of therapeutic radiology at Yale School of Medicine and a member of Yale Cancer Center.

” ‘What was dramatic to me was the relatively high rate of complications and death among surgical patients in the first three months compared with how much better they did than radiosurgery patients after 12 months,’ Yu said. ‘While surgery may be associated with infections and complications in the short-term, it appears that patients healthy enough to undergo surgery live longer.’ “

Patients with Inoperable, Early-Stage Lung Cancer who Receive Stereotactic Body Radiation Therapy Have 40% Five-Year Survival Rate

The gist: This article discusses a clinical trial—a research study with volunteer patients. The trial tested a radiation treatment for inoperable, early-stage lung cancer. The treatment is called stereotactic body radiation therapy (SBRT). The clinical trial ended in 2008, but researchers have been following the patients who participated. They have now reported that 40% of the patients in the trial were still alive five years after SBRT treatment. These numbers are “encouraging” since conventional radiation therapy has not been very effective for people with inoperable lung cancer.

“Patients with inoperable, early-stage lung cancer who receive stereotactic body radiation therapy (SBRT) have a five-year survival rate of 40 percent, according to research presented today at the American Society for Radiation Oncology’s (ASTRO’s) 56th Annual Meeting. Such a positive survival rate is encouraging considering that historically conventional RT resulted in poor tumor control for patients with inoperable lung cancer. This study is an update of RTOG 02362, originally published in 20101, and also conducted by the original researchers to evaluate tumor control rates and side effects for patients at five years post-treatment.

“RTOG 0236 was a Phase II North American multicenter trial from May 2004 until October 2006 of patients age 18 and older with biopsy-proven peripheral T1-T2 N0M0 non-small cell lung cancer (early stage with no lymph node involvement or metastases). Patients in the study all had medical conditions that precluded them from surgery, so they received SBRT, a specialized type of external beam therapy that uses focused radiation beams at a tumor using detailed imaging. SBRT delivers high doses of radiation to the tumor in a decreased amount of treatment time, compared to standard RT, while minimizing exposure to surrounding healthy organs. SBRT appeared to improve tumor control, as suggested by the initial study results for RTOG 0236.

“A total of 59 patients were accrued for the study, and 55 were evaluable (44 patients with T1 tumors and 11 patients with T2 tumors). Patients each received three fractions of 18 Gy (54 Gy total) of SBRT, and treatment lasted between one-and-a-half to two weeks.”

New Prostate Cancer Treatment Convenient, Less Expensive, but May be Riskier

“A faster and less expensive form of radiotherapy for treating prostate cancer may come at a price, according to a new study by Yale School of Medicine researchers—a higher rate of urinary complications.

“The standard external beam radiation therapy for prostate cancer is called intensity modulated radiation therapy (IMRT). Stereotactic body radiotherapy (SBRT) is a newer treatment that delivers a greater dose of radiation per treatment than IMRT. As a result, patients receiving SBRT can complete an entire course of treatment in one to two weeks, compared to seven to nine weeks for IMRT. There have been few studies comparing the costs of these treatments, and their toxicity.”

Local Radiotherapy May Allow Lung Cancer Patients to Stay on Xalkori Longer

Crizotinib (Xalkori) is effective for patients with non-small cell lung cancer (NSCLC) who have a mutation in the ALK gene, but their cancer usually develops resistance to the drug. However, this resistance may affect only part of the cancer, while the majority of the disease still responds to Xalkori. In such cases, localized radiation may be used to destroy the resistant part of the cancer (a technique dubbed ‘weeding the garden’) while patients continue to take Xalkori. In a small study, patients treated with this method could take Xalkori almost three times longer than those not eligible for the treatment. Longer times on Xalkori were associated with higher rates of 2-year survival. The average time without further relapse after the first radiation treatment was 5.5 months, and patients could be treated multiple times. Similar approaches may be effective with other targeted therapies.