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In a phase 2 trial, the 2-year overall survival rate was 51.3% when twice-daily TRT was given at a dose of 45 Gy in 30 fractions and 75% when it was given at a dose of 60 Gy in 40 fractions in patients with LS-SCLC. The two treatment arms had similar safety and quality of life outcomes.
The higher dose “did not add toxicity,” a significant concern with higher radiation doses, said Bjorn Gronberg, MD, PhD, of the Norwegian University of Science and Technology in Trondheim, when presenting this study at the European Society for Medical Oncology Virtual Congress 2020.
However, the discussant for this study pointed out several limitations of the trial and concluded that the 45 Gy dose should remain the standard of care.
Dr. Gonberg explained that concurrent platinum/etoposide (PE) chemotherapy and TRT is the standard treatment for LS-SCLC, and the most recommended schedule for TRT is twice daily at 45 Gy in 30 fractions. He noted, however, that “there’s clearly a need for better treatment” because less than 30% of patients are cured.
“We hypothesized that increasing the dose of radiotherapy might improve survival,” he said.
Study details
Dr. Gonberg and colleagues conducted a phase 2 trial of patients with stage I-III SCLC confined to one hemithorax plus regional lymph nodes. The trial enrolled 176 patients and randomized 170 of them.
The patients received four courses of PE 3 weeks apart. For TRT, 81 patients were randomized to 45 Gy in 30 fractions, and 89 patients were randomized to 60 Gy in 40 fractions, with 10 fractions per week starting with the second PE course.
All patients who responded to chemoradiotherapy were offered prophylactic cranial irradiation at 25 Gy in 10 fractions or 30 Gy in 15 fractions.
Baseline characteristics were well balanced between the treatment arms. The median age was 65 years in both arms, and most patients were women (60.5% in the 45 Gy arm and 56% in the 60 Gy arm).
The mean number of chemotherapy courses was 3.8 in each arm, about 85% of patients received prophylactic cranial radiation, and roughly half received second-line chemotherapy. Overall, 73 patients completed TRT in the 45 Gy arm, and 81 completed TRT in the 60 Gy arm.
Efficacy
There was no significant difference in overall response rate between the treatment arms. It was 81.6% in the 45 Gy arm and 82.1% in the 60 Gy arm (P = .81).
Similarly, there was no significant difference in progression-free survival. The median progression-free survival was 11.1 months in the lower-dose arm and 18.7 months in the higher-dose arm (P = .22).
Still, there was a significant difference in overall survival between the arms. The 2-year overall survival rate was 51.3% in the lower-dose arm and 75% in the higher-dose arm (P = .002). The median overall survival was 24 months and 37.2 months, respectively (P = .034).
Discussant Corinne Faivre-Finn, MD, PhD, of the University of Manchester (England), cautioned that the lower-dose arm appeared to underperform, compared with prior research.
Additionally, “the survival curves separate at about 9 months, [with a] significant difference at 2 years, but the survival curves are coming back together at around 5 years, and that shows that there is a small difference in terms of long-term cure,” she said.
Safety
There were no significant differences in toxicity between the treatment arms.
Dr. Gronberg noted that esophagitis is considered the main dose-limiting toxicity with TRT, but there was no difference in incidence between the two arms (P = .916). Grade 3 esophagitis occurred in 18.4% of patients in the lower-dose arm and 19% of those in the higher-dose arm. There was no grade 4 esophagitis.
Rates of grade 3 and 4 neutropenic infections were higher in the lower-dose arm than in the higher-dose arm, but the difference was not statistically significant (P = .08).
There were also no significant differences in quality of life surveys that patients filled out periodically from baseline until week 52.
“Not so surprisingly,” Dr. Gronberg said, dysphagia was more common at the end of TRT. However, patients had recovered to baseline levels at week 22.
“There’s no difference in the maximum dysphagia reported between the treatment arms, but ... patients in the high-dose arm needed longer time to recover from dysphagia,” Dr. Gronberg said.
Scores for dyspnea, physical function, and global quality of life were similar between the treatment arms.
The similar toxicity between the arms “is quite puzzling,” Dr. Faivre-Finn said, given the 33% increase in radiation dose in the experimental arm. She said this “probably points out an imbalance in some of the factors” between the groups, including tumor volume and doses to organs at risk, which were not reported.
“There are some important missing data, in terms of interpretation of results,” she said.
Given the limitations, and the fact that the study population was relatively small, Dr. Faivre-Finn said “the results cannot be considered definitive and practice changing,” pending additional study.
“So my final conclusion is that twice-a-day radiotherapy at a dose of 45 Gy remains the standard of care, as recommended in the recently published ASTRO [American Society for Radiation Oncology] guidelines,” Dr. Faivre-Finn said.
The study was funded by the Norwegian Cancer Society, the Nordic Cancer Union, and the Norwegian University of Science and Technology. Dr. Gronberg disclosed relationships with Pfizer, Roche, Eli Lilly, and other companies. Dr. Faivre-Finn disclosed relationships with AstraZeneca, Merck, Pfizer, Elekta, and Boehringer Ingelheim.
SOURCE: Gronberg B et al. ESMO 2020, Abstract 1783O.
In a phase 2 trial, the 2-year overall survival rate was 51.3% when twice-daily TRT was given at a dose of 45 Gy in 30 fractions and 75% when it was given at a dose of 60 Gy in 40 fractions in patients with LS-SCLC. The two treatment arms had similar safety and quality of life outcomes.
The higher dose “did not add toxicity,” a significant concern with higher radiation doses, said Bjorn Gronberg, MD, PhD, of the Norwegian University of Science and Technology in Trondheim, when presenting this study at the European Society for Medical Oncology Virtual Congress 2020.
However, the discussant for this study pointed out several limitations of the trial and concluded that the 45 Gy dose should remain the standard of care.
Dr. Gonberg explained that concurrent platinum/etoposide (PE) chemotherapy and TRT is the standard treatment for LS-SCLC, and the most recommended schedule for TRT is twice daily at 45 Gy in 30 fractions. He noted, however, that “there’s clearly a need for better treatment” because less than 30% of patients are cured.
“We hypothesized that increasing the dose of radiotherapy might improve survival,” he said.
Study details
Dr. Gonberg and colleagues conducted a phase 2 trial of patients with stage I-III SCLC confined to one hemithorax plus regional lymph nodes. The trial enrolled 176 patients and randomized 170 of them.
The patients received four courses of PE 3 weeks apart. For TRT, 81 patients were randomized to 45 Gy in 30 fractions, and 89 patients were randomized to 60 Gy in 40 fractions, with 10 fractions per week starting with the second PE course.
All patients who responded to chemoradiotherapy were offered prophylactic cranial irradiation at 25 Gy in 10 fractions or 30 Gy in 15 fractions.
Baseline characteristics were well balanced between the treatment arms. The median age was 65 years in both arms, and most patients were women (60.5% in the 45 Gy arm and 56% in the 60 Gy arm).
The mean number of chemotherapy courses was 3.8 in each arm, about 85% of patients received prophylactic cranial radiation, and roughly half received second-line chemotherapy. Overall, 73 patients completed TRT in the 45 Gy arm, and 81 completed TRT in the 60 Gy arm.
Efficacy
There was no significant difference in overall response rate between the treatment arms. It was 81.6% in the 45 Gy arm and 82.1% in the 60 Gy arm (P = .81).
Similarly, there was no significant difference in progression-free survival. The median progression-free survival was 11.1 months in the lower-dose arm and 18.7 months in the higher-dose arm (P = .22).
Still, there was a significant difference in overall survival between the arms. The 2-year overall survival rate was 51.3% in the lower-dose arm and 75% in the higher-dose arm (P = .002). The median overall survival was 24 months and 37.2 months, respectively (P = .034).
Discussant Corinne Faivre-Finn, MD, PhD, of the University of Manchester (England), cautioned that the lower-dose arm appeared to underperform, compared with prior research.
Additionally, “the survival curves separate at about 9 months, [with a] significant difference at 2 years, but the survival curves are coming back together at around 5 years, and that shows that there is a small difference in terms of long-term cure,” she said.
Safety
There were no significant differences in toxicity between the treatment arms.
Dr. Gronberg noted that esophagitis is considered the main dose-limiting toxicity with TRT, but there was no difference in incidence between the two arms (P = .916). Grade 3 esophagitis occurred in 18.4% of patients in the lower-dose arm and 19% of those in the higher-dose arm. There was no grade 4 esophagitis.
Rates of grade 3 and 4 neutropenic infections were higher in the lower-dose arm than in the higher-dose arm, but the difference was not statistically significant (P = .08).
There were also no significant differences in quality of life surveys that patients filled out periodically from baseline until week 52.
“Not so surprisingly,” Dr. Gronberg said, dysphagia was more common at the end of TRT. However, patients had recovered to baseline levels at week 22.
“There’s no difference in the maximum dysphagia reported between the treatment arms, but ... patients in the high-dose arm needed longer time to recover from dysphagia,” Dr. Gronberg said.
Scores for dyspnea, physical function, and global quality of life were similar between the treatment arms.
The similar toxicity between the arms “is quite puzzling,” Dr. Faivre-Finn said, given the 33% increase in radiation dose in the experimental arm. She said this “probably points out an imbalance in some of the factors” between the groups, including tumor volume and doses to organs at risk, which were not reported.
“There are some important missing data, in terms of interpretation of results,” she said.
Given the limitations, and the fact that the study population was relatively small, Dr. Faivre-Finn said “the results cannot be considered definitive and practice changing,” pending additional study.
“So my final conclusion is that twice-a-day radiotherapy at a dose of 45 Gy remains the standard of care, as recommended in the recently published ASTRO [American Society for Radiation Oncology] guidelines,” Dr. Faivre-Finn said.
The study was funded by the Norwegian Cancer Society, the Nordic Cancer Union, and the Norwegian University of Science and Technology. Dr. Gronberg disclosed relationships with Pfizer, Roche, Eli Lilly, and other companies. Dr. Faivre-Finn disclosed relationships with AstraZeneca, Merck, Pfizer, Elekta, and Boehringer Ingelheim.
SOURCE: Gronberg B et al. ESMO 2020, Abstract 1783O.
In a phase 2 trial, the 2-year overall survival rate was 51.3% when twice-daily TRT was given at a dose of 45 Gy in 30 fractions and 75% when it was given at a dose of 60 Gy in 40 fractions in patients with LS-SCLC. The two treatment arms had similar safety and quality of life outcomes.
The higher dose “did not add toxicity,” a significant concern with higher radiation doses, said Bjorn Gronberg, MD, PhD, of the Norwegian University of Science and Technology in Trondheim, when presenting this study at the European Society for Medical Oncology Virtual Congress 2020.
However, the discussant for this study pointed out several limitations of the trial and concluded that the 45 Gy dose should remain the standard of care.
Dr. Gonberg explained that concurrent platinum/etoposide (PE) chemotherapy and TRT is the standard treatment for LS-SCLC, and the most recommended schedule for TRT is twice daily at 45 Gy in 30 fractions. He noted, however, that “there’s clearly a need for better treatment” because less than 30% of patients are cured.
“We hypothesized that increasing the dose of radiotherapy might improve survival,” he said.
Study details
Dr. Gonberg and colleagues conducted a phase 2 trial of patients with stage I-III SCLC confined to one hemithorax plus regional lymph nodes. The trial enrolled 176 patients and randomized 170 of them.
The patients received four courses of PE 3 weeks apart. For TRT, 81 patients were randomized to 45 Gy in 30 fractions, and 89 patients were randomized to 60 Gy in 40 fractions, with 10 fractions per week starting with the second PE course.
All patients who responded to chemoradiotherapy were offered prophylactic cranial irradiation at 25 Gy in 10 fractions or 30 Gy in 15 fractions.
Baseline characteristics were well balanced between the treatment arms. The median age was 65 years in both arms, and most patients were women (60.5% in the 45 Gy arm and 56% in the 60 Gy arm).
The mean number of chemotherapy courses was 3.8 in each arm, about 85% of patients received prophylactic cranial radiation, and roughly half received second-line chemotherapy. Overall, 73 patients completed TRT in the 45 Gy arm, and 81 completed TRT in the 60 Gy arm.
Efficacy
There was no significant difference in overall response rate between the treatment arms. It was 81.6% in the 45 Gy arm and 82.1% in the 60 Gy arm (P = .81).
Similarly, there was no significant difference in progression-free survival. The median progression-free survival was 11.1 months in the lower-dose arm and 18.7 months in the higher-dose arm (P = .22).
Still, there was a significant difference in overall survival between the arms. The 2-year overall survival rate was 51.3% in the lower-dose arm and 75% in the higher-dose arm (P = .002). The median overall survival was 24 months and 37.2 months, respectively (P = .034).
Discussant Corinne Faivre-Finn, MD, PhD, of the University of Manchester (England), cautioned that the lower-dose arm appeared to underperform, compared with prior research.
Additionally, “the survival curves separate at about 9 months, [with a] significant difference at 2 years, but the survival curves are coming back together at around 5 years, and that shows that there is a small difference in terms of long-term cure,” she said.
Safety
There were no significant differences in toxicity between the treatment arms.
Dr. Gronberg noted that esophagitis is considered the main dose-limiting toxicity with TRT, but there was no difference in incidence between the two arms (P = .916). Grade 3 esophagitis occurred in 18.4% of patients in the lower-dose arm and 19% of those in the higher-dose arm. There was no grade 4 esophagitis.
Rates of grade 3 and 4 neutropenic infections were higher in the lower-dose arm than in the higher-dose arm, but the difference was not statistically significant (P = .08).
There were also no significant differences in quality of life surveys that patients filled out periodically from baseline until week 52.
“Not so surprisingly,” Dr. Gronberg said, dysphagia was more common at the end of TRT. However, patients had recovered to baseline levels at week 22.
“There’s no difference in the maximum dysphagia reported between the treatment arms, but ... patients in the high-dose arm needed longer time to recover from dysphagia,” Dr. Gronberg said.
Scores for dyspnea, physical function, and global quality of life were similar between the treatment arms.
The similar toxicity between the arms “is quite puzzling,” Dr. Faivre-Finn said, given the 33% increase in radiation dose in the experimental arm. She said this “probably points out an imbalance in some of the factors” between the groups, including tumor volume and doses to organs at risk, which were not reported.
“There are some important missing data, in terms of interpretation of results,” she said.
Given the limitations, and the fact that the study population was relatively small, Dr. Faivre-Finn said “the results cannot be considered definitive and practice changing,” pending additional study.
“So my final conclusion is that twice-a-day radiotherapy at a dose of 45 Gy remains the standard of care, as recommended in the recently published ASTRO [American Society for Radiation Oncology] guidelines,” Dr. Faivre-Finn said.
The study was funded by the Norwegian Cancer Society, the Nordic Cancer Union, and the Norwegian University of Science and Technology. Dr. Gronberg disclosed relationships with Pfizer, Roche, Eli Lilly, and other companies. Dr. Faivre-Finn disclosed relationships with AstraZeneca, Merck, Pfizer, Elekta, and Boehringer Ingelheim.
SOURCE: Gronberg B et al. ESMO 2020, Abstract 1783O.
FROM ESMO 2020