IASLC 2018

TORONTO – Prophylactic cranial irradiation, which is standard-of-care practice in patients with small cell lung cancer, also appears to improve intracranial progression-free survival (iPFS) and overall survival in patients with stage IV non–small cell lung cancer (NSCLC), according to findings from a randomized study.

The cumulative incidence of brain metastases at 2 years was 22% in 41 patients who received prophylactic cranial irradiation (PCI), compared with 52% in 43 patients who received standard care with first- and second-generation tyrosine kinase inhibitors (TKIs) without PCI, Oscar Arrieta, MD, reported at the World Conference on Lung Cancer.

PCI was associated with lower odds of progression to the CNS (odds ratio, 0.16), Dr. Arrieta, of the National Cancer Institute of Mexico, Mexico City, said at the meeting sponsored by the International Association for the Study of Lung Cancer. Further, the relative risk for iPFS in patients with an epithelial growth factor receptor (EGFR) or anaplastic lymphoma kinase mutation (ALK), who comprised 70% of patients in both groups, was 0.29 with PCI.

Median overall survival in the groups was 42.8 months versus 25.9 months (HR, 0.48).

The burden of brain metastases can impact the quality and length of survival in patients with NSCLC, and because of an aging population and advances in detection and treatment of primary cancers, patients are living longer and thus are more likely to experience brain metastases, Dr. Arrieta said, noting that this is particularly true for patients at high risk, such as those with elevated carcinoembryonic antigen levels.

Although PCI is standard in small cell lung cancer, its role in NSCLC remains controversial because of concerns about neurologic morbidity and lack of overall survival benefit, he explained.

“The objective of this study was to determine if the use of PCI reduced the development of brain metastases and improved the survival in this population without impairing quality of life,” he said.

Study participants were patients with confirmed stage IV NSCLC and adenocarcinoma histology at high risk for developing brain metastasis. PCI in the treatment group was delivered at 25 Gy/10 fractions.

The findings suggest that in NSCLC with a high risk of developing brain metastases who are treated with a first- or second-generation TKI – particularly those with EGFR and ALK mutations – PCI increases iPFS, Dr. Arrieta said.

“The findings can be extrapolated to those treated with third-generation TKIs, which have higher CNS penetration,” he said, noting, however, that access to third-generation TKIs is limited in most developing countries and cost barriers are high.

Of note, the relatively low dose of PCI used in this study was not associated with significant differences in Mini-Mental State Examination or quality of life scores in the short-term. Long-term assessments are needed, he said, concluding that, while additional study is needed to confirm the findings, the results, including the overall survival benefit seen with PCI, “highlight the benefits of this approach, particularly among patients with a high risk of developing brain metastases.”

Invited discussant Nasser Hanna, MD, the Tom and Julie Wood Family Foundation Professor of Lung Cancer Clinical Research at Indiana University, Indianapolis, said the findings of this “interesting and important study,” are intriguing, but agreed that additional study is needed.

“The study is far too small ... to definitively make this conclusion [that PCI improves iPFS in this population]; I would not recommend PCI without confirmatory data from larger, randomized trials,” he said.

Dr. Arrieta reported advisory roles or provision of expert testimony for Eli Lilly, AstraZeneca, Boehringer Ingelheim, Roche, Merck, Takeda, and Bristol-Myers Squibb, and receipt of honoraria and/or research funding from AstraZeneca, Boehringer Ingelheim, Merck, Roche, and Bristol-Myers Squibb. Dr. Nasser reported receiving research grants from Bristol-Myers Squibb, AstraZeneca, Genentech, and Merck.

SOURCE: Arrieta O et al. WCLC 2018, Abstract MA08.02.

TORONTO – Prophylactic cranial irradiation, which is standard-of-care practice in patients with small cell lung cancer, also appears to improve intracranial progression-free survival (iPFS) and overall survival in patients with stage IV non–small cell lung cancer (NSCLC), according to findings from a randomized study.

The cumulative incidence of brain metastases at 2 years was 22% in 41 patients who received prophylactic cranial irradiation (PCI), compared with 52% in 43 patients who received standard care with first- and second-generation tyrosine kinase inhibitors (TKIs) without PCI, Oscar Arrieta, MD, reported at the World Conference on Lung Cancer.

PCI was associated with lower odds of progression to the CNS (odds ratio, 0.16), Dr. Arrieta, of the National Cancer Institute of Mexico, Mexico City, said at the meeting sponsored by the International Association for the Study of Lung Cancer. Further, the relative risk for iPFS in patients with an epithelial growth factor receptor (EGFR) or anaplastic lymphoma kinase mutation (ALK), who comprised 70% of patients in both groups, was 0.29 with PCI.

Median overall survival in the groups was 42.8 months versus 25.9 months (HR, 0.48).

The burden of brain metastases can impact the quality and length of survival in patients with NSCLC, and because of an aging population and advances in detection and treatment of primary cancers, patients are living longer and thus are more likely to experience brain metastases, Dr. Arrieta said, noting that this is particularly true for patients at high risk, such as those with elevated carcinoembryonic antigen levels.

Although PCI is standard in small cell lung cancer, its role in NSCLC remains controversial because of concerns about neurologic morbidity and lack of overall survival benefit, he explained.

“The objective of this study was to determine if the use of PCI reduced the development of brain metastases and improved the survival in this population without impairing quality of life,” he said.

Study participants were patients with confirmed stage IV NSCLC and adenocarcinoma histology at high risk for developing brain metastasis. PCI in the treatment group was delivered at 25 Gy/10 fractions.

The findings suggest that in NSCLC with a high risk of developing brain metastases who are treated with a first- or second-generation TKI – particularly those with EGFR and ALK mutations – PCI increases iPFS, Dr. Arrieta said.

“The findings can be extrapolated to those treated with third-generation TKIs, which have higher CNS penetration,” he said, noting, however, that access to third-generation TKIs is limited in most developing countries and cost barriers are high.

Of note, the relatively low dose of PCI used in this study was not associated with significant differences in Mini-Mental State Examination or quality of life scores in the short-term. Long-term assessments are needed, he said, concluding that, while additional study is needed to confirm the findings, the results, including the overall survival benefit seen with PCI, “highlight the benefits of this approach, particularly among patients with a high risk of developing brain metastases.”

Invited discussant Nasser Hanna, MD, the Tom and Julie Wood Family Foundation Professor of Lung Cancer Clinical Research at Indiana University, Indianapolis, said the findings of this “interesting and important study,” are intriguing, but agreed that additional study is needed.

“The study is far too small ... to definitively make this conclusion [that PCI improves iPFS in this population]; I would not recommend PCI without confirmatory data from larger, randomized trials,” he said.

Dr. Arrieta reported advisory roles or provision of expert testimony for Eli Lilly, AstraZeneca, Boehringer Ingelheim, Roche, Merck, Takeda, and Bristol-Myers Squibb, and receipt of honoraria and/or research funding from AstraZeneca, Boehringer Ingelheim, Merck, Roche, and Bristol-Myers Squibb. Dr. Nasser reported receiving research grants from Bristol-Myers Squibb, AstraZeneca, Genentech, and Merck.

SOURCE: Arrieta O et al. WCLC 2018, Abstract MA08.02.

TORONTO – Prophylactic cranial irradiation, which is standard-of-care practice in patients with small cell lung cancer, also appears to improve intracranial progression-free survival (iPFS) and overall survival in patients with stage IV non–small cell lung cancer (NSCLC), according to findings from a randomized study.

The cumulative incidence of brain metastases at 2 years was 22% in 41 patients who received prophylactic cranial irradiation (PCI), compared with 52% in 43 patients who received standard care with first- and second-generation tyrosine kinase inhibitors (TKIs) without PCI, Oscar Arrieta, MD, reported at the World Conference on Lung Cancer.

PCI was associated with lower odds of progression to the CNS (odds ratio, 0.16), Dr. Arrieta, of the National Cancer Institute of Mexico, Mexico City, said at the meeting sponsored by the International Association for the Study of Lung Cancer. Further, the relative risk for iPFS in patients with an epithelial growth factor receptor (EGFR) or anaplastic lymphoma kinase mutation (ALK), who comprised 70% of patients in both groups, was 0.29 with PCI.

Median overall survival in the groups was 42.8 months versus 25.9 months (HR, 0.48).

The burden of brain metastases can impact the quality and length of survival in patients with NSCLC, and because of an aging population and advances in detection and treatment of primary cancers, patients are living longer and thus are more likely to experience brain metastases, Dr. Arrieta said, noting that this is particularly true for patients at high risk, such as those with elevated carcinoembryonic antigen levels.

Although PCI is standard in small cell lung cancer, its role in NSCLC remains controversial because of concerns about neurologic morbidity and lack of overall survival benefit, he explained.

“The objective of this study was to determine if the use of PCI reduced the development of brain metastases and improved the survival in this population without impairing quality of life,” he said.

Study participants were patients with confirmed stage IV NSCLC and adenocarcinoma histology at high risk for developing brain metastasis. PCI in the treatment group was delivered at 25 Gy/10 fractions.

The findings suggest that in NSCLC with a high risk of developing brain metastases who are treated with a first- or second-generation TKI – particularly those with EGFR and ALK mutations – PCI increases iPFS, Dr. Arrieta said.

“The findings can be extrapolated to those treated with third-generation TKIs, which have higher CNS penetration,” he said, noting, however, that access to third-generation TKIs is limited in most developing countries and cost barriers are high.

Of note, the relatively low dose of PCI used in this study was not associated with significant differences in Mini-Mental State Examination or quality of life scores in the short-term. Long-term assessments are needed, he said, concluding that, while additional study is needed to confirm the findings, the results, including the overall survival benefit seen with PCI, “highlight the benefits of this approach, particularly among patients with a high risk of developing brain metastases.”

Invited discussant Nasser Hanna, MD, the Tom and Julie Wood Family Foundation Professor of Lung Cancer Clinical Research at Indiana University, Indianapolis, said the findings of this “interesting and important study,” are intriguing, but agreed that additional study is needed.

“The study is far too small ... to definitively make this conclusion [that PCI improves iPFS in this population]; I would not recommend PCI without confirmatory data from larger, randomized trials,” he said.

Dr. Arrieta reported advisory roles or provision of expert testimony for Eli Lilly, AstraZeneca, Boehringer Ingelheim, Roche, Merck, Takeda, and Bristol-Myers Squibb, and receipt of honoraria and/or research funding from AstraZeneca, Boehringer Ingelheim, Merck, Roche, and Bristol-Myers Squibb. Dr. Nasser reported receiving research grants from Bristol-Myers Squibb, AstraZeneca, Genentech, and Merck.

SOURCE: Arrieta O et al. WCLC 2018, Abstract MA08.02.

TORONTO – Concurrent atezolizumab immunotherapy and chemoradiation followed by atezolizumab consolidation and maintenance was safe and showed promising efficacy in patients with locally advanced non–small cell lung cancer (LA-NSCLC) in the phase 2 DETERRED trial.

In part 1 of the single-institution study, 10 patients underwent chemoradiation therapy (CRT) with low-dose carboplatin/paclitaxel followed by high-dose consolidation chemotherapy plus atezolizumab and atezolizumab maintenance for 1 year. Six patients in this group (60%) experienced grade 3 or higher adverse events (AEs). In part 2 of the study, 30 patients received concurrent atezolizumab and CRT followed by the same consolidation and maintenance used in part 1, and 17 (57%) experienced grade 3 or higher AEs, Steven H. Lin, MD, reported at the World Conference on Lung Cancer.

Grade 3 or higher AEs were associated with atezolizumab in 30% and 23% of patients in part 1 and part 2, respectively. In part 1 these included dyspnea, arthralgia, and a grade 5 tracheoesophageal fistula, and in part 2 included diarrhea, pneumonitis, nephritis, fatigue, respiratory failure, and heart failure in one patient each, and fatigue in three patients.

Grade 2 radiation pneumonitis was seen in two patients in each group, Dr. Lin of the University of Texas MD Anderson Cancer Center, Houston, said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.

Withdrawals caused by toxicity occurred in three and four patients in part 1 and 2, respectively.

Four patients in part 1 progressed with disease during atezolizumab maintenance and five have died from either tracheoesophageal fistula or grade 5 toxicity. In part 2, six have progressed and five have died, most caused by cancer progression, he said.

Preliminary survival data show a median progression-free survival of 20.1 months in part 1, whereas progression-free survival was not reached in part 2. Median overall survival at 1 year was 60% versus 77% in parts 1 and 2, respectively.

Consolidation immunotherapy with durvalumab after CRT has been the standard of care for LA-NSCLC as established by the phase 3 PACIFIC trial, but evidence from that trial also suggested timing of the start of immunotherapy may be important.

“If patients were randomized less than 14 days after starting durvalumab there was a trend, or suggestion, that there was potentially an improvement in progression-free survival, compared with patients who started durvalumab outside of this window,” Dr. Lin said, noting that this is also supported by some preclinical evidence showing that the effectiveness of immunotherapies may be enhanced when combined with concurrent CRT.

The DETERRED trial evaluated the safety and preliminary efficacy of this approach followed by consolidation full-dose carboplatin/paclitaxel with atezolizumab and maintenance atezolizumab for up to 1 year for LA-NSCLC.

Patients, who had a median age of 66.5 years, were enrolled between February 2016 and April 2018; 15% had stage II disease, 50% had stage IIIA, and 35% had stage IIIB. Most (58%) had adenocarcinoma.

In part 1, standard chemoradiation including low-dose carboplatin/paclitaxel was given for 6 weeks. After CRT completion, patients were given consolidated high-dose chemotherapy with carboplatin/paclitaxel and intravenous atezolizumab was started at that point at a dose of 1,200 mg every 3 weeks for up to 1 year from the first dose. Part 2 was initiated based on the safety data in part 1 showing no concerning toxicities. In part 2, atezolizumab was given concurrently with CRT followed by the same consolidated regimen and maintenance.

“So the take-home message from this study is that the concurrent immunotherapy with atezolizumab and chemoradiation therapy can be administered safely,” Dr. Lin said, adding that grade 3+ pneumonitis is low and not significantly increased with the addition of concurrent atezolizumab with CRT.

Early efficacy analyses also show promising results, but further follow-up is needed, he said.

Trials now being planned include a phase 3 trial comparing the DETERRED and PACIFIC regimens, a phase 1 study comparing durvalumab with radiation to replace chemotherapy in programmed death–ligand 1–high locoregionally advanced NSCLC, and a phase 1 study of nivolumab with radiation to replace chemotherapy in locoregionally advanced NSCLC, he noted.

The DETERRED trial was supported by Genentech. Dr. Lin has received research grants from STCube Pharmaceuticals, Hitachi Chemical Diagnostics, Genentech, New River Labs, and BeyondSpring Pharmaceuticals, and is an advisory board member for AstraZeneca and New River Labs.

[email protected]

SOURCE: Lin SH et al. WCLC 2018, Abstract OA01.06.

TORONTO – Concurrent atezolizumab immunotherapy and chemoradiation followed by atezolizumab consolidation and maintenance was safe and showed promising efficacy in patients with locally advanced non–small cell lung cancer (LA-NSCLC) in the phase 2 DETERRED trial.

In part 1 of the single-institution study, 10 patients underwent chemoradiation therapy (CRT) with low-dose carboplatin/paclitaxel followed by high-dose consolidation chemotherapy plus atezolizumab and atezolizumab maintenance for 1 year. Six patients in this group (60%) experienced grade 3 or higher adverse events (AEs). In part 2 of the study, 30 patients received concurrent atezolizumab and CRT followed by the same consolidation and maintenance used in part 1, and 17 (57%) experienced grade 3 or higher AEs, Steven H. Lin, MD, reported at the World Conference on Lung Cancer.

Grade 3 or higher AEs were associated with atezolizumab in 30% and 23% of patients in part 1 and part 2, respectively. In part 1 these included dyspnea, arthralgia, and a grade 5 tracheoesophageal fistula, and in part 2 included diarrhea, pneumonitis, nephritis, fatigue, respiratory failure, and heart failure in one patient each, and fatigue in three patients.

Grade 2 radiation pneumonitis was seen in two patients in each group, Dr. Lin of the University of Texas MD Anderson Cancer Center, Houston, said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.

Withdrawals caused by toxicity occurred in three and four patients in part 1 and 2, respectively.

Four patients in part 1 progressed with disease during atezolizumab maintenance and five have died from either tracheoesophageal fistula or grade 5 toxicity. In part 2, six have progressed and five have died, most caused by cancer progression, he said.

Preliminary survival data show a median progression-free survival of 20.1 months in part 1, whereas progression-free survival was not reached in part 2. Median overall survival at 1 year was 60% versus 77% in parts 1 and 2, respectively.

Consolidation immunotherapy with durvalumab after CRT has been the standard of care for LA-NSCLC as established by the phase 3 PACIFIC trial, but evidence from that trial also suggested timing of the start of immunotherapy may be important.

“If patients were randomized less than 14 days after starting durvalumab there was a trend, or suggestion, that there was potentially an improvement in progression-free survival, compared with patients who started durvalumab outside of this window,” Dr. Lin said, noting that this is also supported by some preclinical evidence showing that the effectiveness of immunotherapies may be enhanced when combined with concurrent CRT.

The DETERRED trial evaluated the safety and preliminary efficacy of this approach followed by consolidation full-dose carboplatin/paclitaxel with atezolizumab and maintenance atezolizumab for up to 1 year for LA-NSCLC.

Patients, who had a median age of 66.5 years, were enrolled between February 2016 and April 2018; 15% had stage II disease, 50% had stage IIIA, and 35% had stage IIIB. Most (58%) had adenocarcinoma.

In part 1, standard chemoradiation including low-dose carboplatin/paclitaxel was given for 6 weeks. After CRT completion, patients were given consolidated high-dose chemotherapy with carboplatin/paclitaxel and intravenous atezolizumab was started at that point at a dose of 1,200 mg every 3 weeks for up to 1 year from the first dose. Part 2 was initiated based on the safety data in part 1 showing no concerning toxicities. In part 2, atezolizumab was given concurrently with CRT followed by the same consolidated regimen and maintenance.

“So the take-home message from this study is that the concurrent immunotherapy with atezolizumab and chemoradiation therapy can be administered safely,” Dr. Lin said, adding that grade 3+ pneumonitis is low and not significantly increased with the addition of concurrent atezolizumab with CRT.

Early efficacy analyses also show promising results, but further follow-up is needed, he said.

Trials now being planned include a phase 3 trial comparing the DETERRED and PACIFIC regimens, a phase 1 study comparing durvalumab with radiation to replace chemotherapy in programmed death–ligand 1–high locoregionally advanced NSCLC, and a phase 1 study of nivolumab with radiation to replace chemotherapy in locoregionally advanced NSCLC, he noted.

The DETERRED trial was supported by Genentech. Dr. Lin has received research grants from STCube Pharmaceuticals, Hitachi Chemical Diagnostics, Genentech, New River Labs, and BeyondSpring Pharmaceuticals, and is an advisory board member for AstraZeneca and New River Labs.

[email protected]

SOURCE: Lin SH et al. WCLC 2018, Abstract OA01.06.

TORONTO – Concurrent atezolizumab immunotherapy and chemoradiation followed by atezolizumab consolidation and maintenance was safe and showed promising efficacy in patients with locally advanced non–small cell lung cancer (LA-NSCLC) in the phase 2 DETERRED trial.

In part 1 of the single-institution study, 10 patients underwent chemoradiation therapy (CRT) with low-dose carboplatin/paclitaxel followed by high-dose consolidation chemotherapy plus atezolizumab and atezolizumab maintenance for 1 year. Six patients in this group (60%) experienced grade 3 or higher adverse events (AEs). In part 2 of the study, 30 patients received concurrent atezolizumab and CRT followed by the same consolidation and maintenance used in part 1, and 17 (57%) experienced grade 3 or higher AEs, Steven H. Lin, MD, reported at the World Conference on Lung Cancer.

Grade 3 or higher AEs were associated with atezolizumab in 30% and 23% of patients in part 1 and part 2, respectively. In part 1 these included dyspnea, arthralgia, and a grade 5 tracheoesophageal fistula, and in part 2 included diarrhea, pneumonitis, nephritis, fatigue, respiratory failure, and heart failure in one patient each, and fatigue in three patients.

Grade 2 radiation pneumonitis was seen in two patients in each group, Dr. Lin of the University of Texas MD Anderson Cancer Center, Houston, said at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.

Withdrawals caused by toxicity occurred in three and four patients in part 1 and 2, respectively.

Four patients in part 1 progressed with disease during atezolizumab maintenance and five have died from either tracheoesophageal fistula or grade 5 toxicity. In part 2, six have progressed and five have died, most caused by cancer progression, he said.

Preliminary survival data show a median progression-free survival of 20.1 months in part 1, whereas progression-free survival was not reached in part 2. Median overall survival at 1 year was 60% versus 77% in parts 1 and 2, respectively.

Consolidation immunotherapy with durvalumab after CRT has been the standard of care for LA-NSCLC as established by the phase 3 PACIFIC trial, but evidence from that trial also suggested timing of the start of immunotherapy may be important.

“If patients were randomized less than 14 days after starting durvalumab there was a trend, or suggestion, that there was potentially an improvement in progression-free survival, compared with patients who started durvalumab outside of this window,” Dr. Lin said, noting that this is also supported by some preclinical evidence showing that the effectiveness of immunotherapies may be enhanced when combined with concurrent CRT.

The DETERRED trial evaluated the safety and preliminary efficacy of this approach followed by consolidation full-dose carboplatin/paclitaxel with atezolizumab and maintenance atezolizumab for up to 1 year for LA-NSCLC.

Patients, who had a median age of 66.5 years, were enrolled between February 2016 and April 2018; 15% had stage II disease, 50% had stage IIIA, and 35% had stage IIIB. Most (58%) had adenocarcinoma.

In part 1, standard chemoradiation including low-dose carboplatin/paclitaxel was given for 6 weeks. After CRT completion, patients were given consolidated high-dose chemotherapy with carboplatin/paclitaxel and intravenous atezolizumab was started at that point at a dose of 1,200 mg every 3 weeks for up to 1 year from the first dose. Part 2 was initiated based on the safety data in part 1 showing no concerning toxicities. In part 2, atezolizumab was given concurrently with CRT followed by the same consolidated regimen and maintenance.

“So the take-home message from this study is that the concurrent immunotherapy with atezolizumab and chemoradiation therapy can be administered safely,” Dr. Lin said, adding that grade 3+ pneumonitis is low and not significantly increased with the addition of concurrent atezolizumab with CRT.

Early efficacy analyses also show promising results, but further follow-up is needed, he said.

Trials now being planned include a phase 3 trial comparing the DETERRED and PACIFIC regimens, a phase 1 study comparing durvalumab with radiation to replace chemotherapy in programmed death–ligand 1–high locoregionally advanced NSCLC, and a phase 1 study of nivolumab with radiation to replace chemotherapy in locoregionally advanced NSCLC, he noted.

The DETERRED trial was supported by Genentech. Dr. Lin has received research grants from STCube Pharmaceuticals, Hitachi Chemical Diagnostics, Genentech, New River Labs, and BeyondSpring Pharmaceuticals, and is an advisory board member for AstraZeneca and New River Labs.

[email protected]

SOURCE: Lin SH et al. WCLC 2018, Abstract OA01.06.

TORONTO – Brigatinib proved superior to crizotinib for achieving progression-free survival in patients with inhibitor-naive anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancer in the first interim results from the multicenter, open-label, phase 3 ALTA-1L trial.

Sharon Worcester/MDedge News

In fact, the primary endpoint of the study – blinded independent review committee–assessed progression-free survival (PFS) – was met at this first analysis. The next-generation ALK inhibitor brigatinib reduced the chance of progression or death by 51% as compared with crizotinib – the current first-line standard of care in this population, D. Ross Camidge, MD, reported at the World Conference on Lung Cancer.

“At a median follow-up of 9-11 months, 26% [of 137 patients] on the brigatinib arm and 46% [of 138 patients] on the crizotinib arm had experienced a PFS event. Median PFS was not reached for the brigatinib arm and was 9.8 months for the crizotinib arm; the hazard ratio for progression or death was 0.49 and highly statistically significant,” said Dr. Camidge, director of thoracic oncology and the Joyce Zeff Chair in Lung Cancer Research at the University of Colorado Cancer Center, Aurora, at the meeting sponsored by the International Association for the Study of Lung Cancer.

The findings were published simultaneously in the New England Journal of Medicine.

The 12-month PFS rate estimate was 67% for brigatinib and 43% for crizotinib, and the investigator-assessed hazard ratio for PFS was 0.45. Overall survival data are immature, Dr. Camidge added, noting that the PFS hazard ratios for those with versus those without prior chemotherapy were 0.35 and 0.55, respectively.

“PFS consistently favored brigatinib across all other subgroups,” he said. “Although the confidence intervals overlap, the effect size appears greater among those with baseline [CNS] disease than among those without [HR, 0.2 vs. 0.72].”

Data suggest that CNS progression among those with CNS disease at baseline tends to be an earlier event than either extra-CNS progression in general or CNS progression in those without baseline CNS disease. “Consequently, this first interim analysis may be preferentially emphasizing drug efficacy differences within the subgroup in whom the earlier progression events are occurring,” Dr. Camidge said.

As for overall objective responses, the rates were numerically higher with brigatinib versus crizotinib (70% vs. 60%), but were not statistically different in the two groups. “However, the median duration of confirmed responses was not reached for brigatinib and [was] 11.1 months with crizotinib, with the 12-month [probability] of sustained response being 75% for brigatinib and 41% for crizotinib,” he added.

Further, among those with measurable CNS lesions, brigatinib demonstrated a significantly higher intracranial response rate of 78% versus 29% (odds ratio, 10.42), and when those with nonmeasurable CNS disease were included in the intracranial response assessment, the odds ratio was 13.

Median intracranial PFS among those with CNS involvement at baseline was not reached in the brigatinib arm versus 5.6 months with crizotinib, for a highly statistically significant hazard ratio of 0.27. “Which, given that the median PFS for crizotinib in the overall population ... was 9.8 months, again emphasizes how CNS events in this subgroup tend to occur early,” he noted.

Study subjects had stage IIIB/IV ALK-positive non–small cell lung cancer (NSCLC) based on local ALK testing, Eastern Cooperative Oncology Group performance status of 0-2, no more than one prior systemic therapy for locally advanced/metastatic NSCLC, and no prior ALK inhibitor therapy, Dr. Camidge said, noting that asymptomatic, untreated brain metastases were allowed and crossover to the brigatinib arm was permitted for those with blinded independent review committee–assessed progression on crizotinib.

Those randomized to the brigatinib arm had a median age of 58 years and received 180 mg daily with a 7-day lead-in at 90 mg. Those randomized to the crizotinib group had a median age of 60 years and received 250 mg twice daily. Prior chemotherapy for advanced disease was received by 26% and 27% and brain metastasis was present in 29% and 30% of patients in the arms, respectively.

The most common treatment-emergent adverse events of grade 3 or higher in the brigatinib patients were laboratory abnormalities such as creatinine phosphokinase, lipase, and amylase increases, and the most common in the crizotinib group were gastrointestinal effects, transaminitis, bradycardia, peripheral edema, and vision disturbances.

Discontinuations caused by adverse events occurred in 12% and 9% of the brigatinib and crizotinib patients, respectively, he said. No clinical cases of pancreatitis occurred in either arm, there was no difference in the incidence of any grade myalgia or musculoskeletal pain between arms, and there was no grade 3 or greater myalgia or musculoskeletal pain reported.

Early-onset interstitial lung disease, however, “appears to be a unique side effect of brigatinib,” Dr. Camidge noted.

Although interstitial lung disease/pneumonitis occurred in both groups, onset at days 3-8 after treatment initiation occurred only with brigatinib, he said, adding that “it only occurred in 3% of cases – half the rate seen in the postcrizotinib setting.”

The PROFILE 1014 study established crizotinib as the standard first-line therapy for advanced ALK-rearranged NSCLC, showing superior PFS versus pemetrexed doublet chemotherapy (HR, 0.45), but median PFS with crizotinib in that trial was only 10.9 months, Dr. Camidge said.

The next-generation ALK inhibitor brigatinib, however, has demonstrated broad preclinical activity against ALK resistance mutations, has excellent CNS penetration, and is the only ALK inhibitor with marked activity against multiple epidermal growth factor receptor–mutant cell lines, he said. “It has already shown significant activity both within the CNS and extracranially in the postcrizotinib setting, where it has consistently demonstrated the longest reported median PFS [up to 16.7 months] of any licensed or experimental ALK inhibitor.”

The ALTA-1L study provides a head-to-head comparison of brigatinib and crizotinib in a real-world setting, and the findings demonstrate that “brigatinib represents a promising new treatment for inhibitor-naive, ALK-rearranged NSCLC,” he said.

In a press statement, Dr. Camidge further stated that, based on these findings, brigatinib is set to become a first-line treatment option for ALK-positive lung cancer, adding that, “even with only 9-11 months of follow-up, the efficacy of brigatinib is clearly superior to crizotinib. A lot of the initial difference is driven by an effect on brain metastases, which tend to be an earlier progression event. However, once differences in control of disease outside the brain have time to manifest, it is possible the PFS improvement may increase.”

Both Dr. Camidge and invited discussant Fiona Blackhall, PhD, noted that the tolerability of brigatinib may be “even better in the real world,” as most of the 29% of patients on the brigatinib arm with adverse event–related dose reductions had “paper toxicities” for which the clinical impact is not well understood.

The rate of dose reductions for adverse events with brigatinib was higher in ALTA-1L than that seen in earlier studies of the second-generation ALK inhibitor alectinib, said Dr. Blackhall, professor and chair in thoracic oncology at the University of Manchester (England).

“We need to be sure that these dose reductions are appropriate and not potentially compromising efficacy,” she added.

Dr. Blackhall also suggested that sequential use of crizotinib and other ALK inhibitors like brigatinib should be evaluated and that the potential impact of ALK inhibitor selection “on the spectrum and type of resistance mutations and mechanisms” should be considered.

“Brigatinib is a new first-line treatment option for patients with ALK-positive non–small cell lung cancer. ... But in the absence of direct comparison of next-generation ALK inhibitors, it is going to take some time before we can determine whether there is indeed – if there ever will be – a ‘best’ ALK inhibitor for our patients,” she said.

Dr. Camidge has received honoraria from Arrys/Kyn, AstraZeneca, Biothera, Celgene, Clovis Oncology, Daiichi Sankyo, G1 Therapeutics, Genoptix, Hansoh, Ignyta, Lycera, Mersana Therapeutics, Novartis, Orion, Revolution Medicines, Roche/Genentech, and Takeda, and has received research funding from ARIADTakeda. Dr. Blackhall reported research funding from Amgen, AstraZeneca, Novartis, and Pfizer, and has served has an advisory board member, consultant, or speaker for AbbVie, Boehringer Ingelheim, Cell Medica, Medivation, Merck, Regeneron, Roche, and Takeda.

[email protected]

SOURCE: Camidge DR et al. WCLC 2018, Abstract PL02.03.

TORONTO – Brigatinib proved superior to crizotinib for achieving progression-free survival in patients with inhibitor-naive anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancer in the first interim results from the multicenter, open-label, phase 3 ALTA-1L trial.

Sharon Worcester/MDedge News

In fact, the primary endpoint of the study – blinded independent review committee–assessed progression-free survival (PFS) – was met at this first analysis. The next-generation ALK inhibitor brigatinib reduced the chance of progression or death by 51% as compared with crizotinib – the current first-line standard of care in this population, D. Ross Camidge, MD, reported at the World Conference on Lung Cancer.

“At a median follow-up of 9-11 months, 26% [of 137 patients] on the brigatinib arm and 46% [of 138 patients] on the crizotinib arm had experienced a PFS event. Median PFS was not reached for the brigatinib arm and was 9.8 months for the crizotinib arm; the hazard ratio for progression or death was 0.49 and highly statistically significant,” said Dr. Camidge, director of thoracic oncology and the Joyce Zeff Chair in Lung Cancer Research at the University of Colorado Cancer Center, Aurora, at the meeting sponsored by the International Association for the Study of Lung Cancer.

The findings were published simultaneously in the New England Journal of Medicine.

The 12-month PFS rate estimate was 67% for brigatinib and 43% for crizotinib, and the investigator-assessed hazard ratio for PFS was 0.45. Overall survival data are immature, Dr. Camidge added, noting that the PFS hazard ratios for those with versus those without prior chemotherapy were 0.35 and 0.55, respectively.

“PFS consistently favored brigatinib across all other subgroups,” he said. “Although the confidence intervals overlap, the effect size appears greater among those with baseline [CNS] disease than among those without [HR, 0.2 vs. 0.72].”

Data suggest that CNS progression among those with CNS disease at baseline tends to be an earlier event than either extra-CNS progression in general or CNS progression in those without baseline CNS disease. “Consequently, this first interim analysis may be preferentially emphasizing drug efficacy differences within the subgroup in whom the earlier progression events are occurring,” Dr. Camidge said.

As for overall objective responses, the rates were numerically higher with brigatinib versus crizotinib (70% vs. 60%), but were not statistically different in the two groups. “However, the median duration of confirmed responses was not reached for brigatinib and [was] 11.1 months with crizotinib, with the 12-month [probability] of sustained response being 75% for brigatinib and 41% for crizotinib,” he added.

Further, among those with measurable CNS lesions, brigatinib demonstrated a significantly higher intracranial response rate of 78% versus 29% (odds ratio, 10.42), and when those with nonmeasurable CNS disease were included in the intracranial response assessment, the odds ratio was 13.

Median intracranial PFS among those with CNS involvement at baseline was not reached in the brigatinib arm versus 5.6 months with crizotinib, for a highly statistically significant hazard ratio of 0.27. “Which, given that the median PFS for crizotinib in the overall population ... was 9.8 months, again emphasizes how CNS events in this subgroup tend to occur early,” he noted.

Study subjects had stage IIIB/IV ALK-positive non–small cell lung cancer (NSCLC) based on local ALK testing, Eastern Cooperative Oncology Group performance status of 0-2, no more than one prior systemic therapy for locally advanced/metastatic NSCLC, and no prior ALK inhibitor therapy, Dr. Camidge said, noting that asymptomatic, untreated brain metastases were allowed and crossover to the brigatinib arm was permitted for those with blinded independent review committee–assessed progression on crizotinib.

Those randomized to the brigatinib arm had a median age of 58 years and received 180 mg daily with a 7-day lead-in at 90 mg. Those randomized to the crizotinib group had a median age of 60 years and received 250 mg twice daily. Prior chemotherapy for advanced disease was received by 26% and 27% and brain metastasis was present in 29% and 30% of patients in the arms, respectively.

The most common treatment-emergent adverse events of grade 3 or higher in the brigatinib patients were laboratory abnormalities such as creatinine phosphokinase, lipase, and amylase increases, and the most common in the crizotinib group were gastrointestinal effects, transaminitis, bradycardia, peripheral edema, and vision disturbances.

Discontinuations caused by adverse events occurred in 12% and 9% of the brigatinib and crizotinib patients, respectively, he said. No clinical cases of pancreatitis occurred in either arm, there was no difference in the incidence of any grade myalgia or musculoskeletal pain between arms, and there was no grade 3 or greater myalgia or musculoskeletal pain reported.

Early-onset interstitial lung disease, however, “appears to be a unique side effect of brigatinib,” Dr. Camidge noted.

Although interstitial lung disease/pneumonitis occurred in both groups, onset at days 3-8 after treatment initiation occurred only with brigatinib, he said, adding that “it only occurred in 3% of cases – half the rate seen in the postcrizotinib setting.”

The PROFILE 1014 study established crizotinib as the standard first-line therapy for advanced ALK-rearranged NSCLC, showing superior PFS versus pemetrexed doublet chemotherapy (HR, 0.45), but median PFS with crizotinib in that trial was only 10.9 months, Dr. Camidge said.

The next-generation ALK inhibitor brigatinib, however, has demonstrated broad preclinical activity against ALK resistance mutations, has excellent CNS penetration, and is the only ALK inhibitor with marked activity against multiple epidermal growth factor receptor–mutant cell lines, he said. “It has already shown significant activity both within the CNS and extracranially in the postcrizotinib setting, where it has consistently demonstrated the longest reported median PFS [up to 16.7 months] of any licensed or experimental ALK inhibitor.”

The ALTA-1L study provides a head-to-head comparison of brigatinib and crizotinib in a real-world setting, and the findings demonstrate that “brigatinib represents a promising new treatment for inhibitor-naive, ALK-rearranged NSCLC,” he said.

In a press statement, Dr. Camidge further stated that, based on these findings, brigatinib is set to become a first-line treatment option for ALK-positive lung cancer, adding that, “even with only 9-11 months of follow-up, the efficacy of brigatinib is clearly superior to crizotinib. A lot of the initial difference is driven by an effect on brain metastases, which tend to be an earlier progression event. However, once differences in control of disease outside the brain have time to manifest, it is possible the PFS improvement may increase.”

Both Dr. Camidge and invited discussant Fiona Blackhall, PhD, noted that the tolerability of brigatinib may be “even better in the real world,” as most of the 29% of patients on the brigatinib arm with adverse event–related dose reductions had “paper toxicities” for which the clinical impact is not well understood.

The rate of dose reductions for adverse events with brigatinib was higher in ALTA-1L than that seen in earlier studies of the second-generation ALK inhibitor alectinib, said Dr. Blackhall, professor and chair in thoracic oncology at the University of Manchester (England).

“We need to be sure that these dose reductions are appropriate and not potentially compromising efficacy,” she added.

Dr. Blackhall also suggested that sequential use of crizotinib and other ALK inhibitors like brigatinib should be evaluated and that the potential impact of ALK inhibitor selection “on the spectrum and type of resistance mutations and mechanisms” should be considered.

“Brigatinib is a new first-line treatment option for patients with ALK-positive non–small cell lung cancer. ... But in the absence of direct comparison of next-generation ALK inhibitors, it is going to take some time before we can determine whether there is indeed – if there ever will be – a ‘best’ ALK inhibitor for our patients,” she said.

Dr. Camidge has received honoraria from Arrys/Kyn, AstraZeneca, Biothera, Celgene, Clovis Oncology, Daiichi Sankyo, G1 Therapeutics, Genoptix, Hansoh, Ignyta, Lycera, Mersana Therapeutics, Novartis, Orion, Revolution Medicines, Roche/Genentech, and Takeda, and has received research funding from ARIADTakeda. Dr. Blackhall reported research funding from Amgen, AstraZeneca, Novartis, and Pfizer, and has served has an advisory board member, consultant, or speaker for AbbVie, Boehringer Ingelheim, Cell Medica, Medivation, Merck, Regeneron, Roche, and Takeda.

[email protected]

SOURCE: Camidge DR et al. WCLC 2018, Abstract PL02.03.

TORONTO – Brigatinib proved superior to crizotinib for achieving progression-free survival in patients with inhibitor-naive anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancer in the first interim results from the multicenter, open-label, phase 3 ALTA-1L trial.

Sharon Worcester/MDedge News

In fact, the primary endpoint of the study – blinded independent review committee–assessed progression-free survival (PFS) – was met at this first analysis. The next-generation ALK inhibitor brigatinib reduced the chance of progression or death by 51% as compared with crizotinib – the current first-line standard of care in this population, D. Ross Camidge, MD, reported at the World Conference on Lung Cancer.

“At a median follow-up of 9-11 months, 26% [of 137 patients] on the brigatinib arm and 46% [of 138 patients] on the crizotinib arm had experienced a PFS event. Median PFS was not reached for the brigatinib arm and was 9.8 months for the crizotinib arm; the hazard ratio for progression or death was 0.49 and highly statistically significant,” said Dr. Camidge, director of thoracic oncology and the Joyce Zeff Chair in Lung Cancer Research at the University of Colorado Cancer Center, Aurora, at the meeting sponsored by the International Association for the Study of Lung Cancer.

The findings were published simultaneously in the New England Journal of Medicine.

The 12-month PFS rate estimate was 67% for brigatinib and 43% for crizotinib, and the investigator-assessed hazard ratio for PFS was 0.45. Overall survival data are immature, Dr. Camidge added, noting that the PFS hazard ratios for those with versus those without prior chemotherapy were 0.35 and 0.55, respectively.

“PFS consistently favored brigatinib across all other subgroups,” he said. “Although the confidence intervals overlap, the effect size appears greater among those with baseline [CNS] disease than among those without [HR, 0.2 vs. 0.72].”

Data suggest that CNS progression among those with CNS disease at baseline tends to be an earlier event than either extra-CNS progression in general or CNS progression in those without baseline CNS disease. “Consequently, this first interim analysis may be preferentially emphasizing drug efficacy differences within the subgroup in whom the earlier progression events are occurring,” Dr. Camidge said.

As for overall objective responses, the rates were numerically higher with brigatinib versus crizotinib (70% vs. 60%), but were not statistically different in the two groups. “However, the median duration of confirmed responses was not reached for brigatinib and [was] 11.1 months with crizotinib, with the 12-month [probability] of sustained response being 75% for brigatinib and 41% for crizotinib,” he added.

Further, among those with measurable CNS lesions, brigatinib demonstrated a significantly higher intracranial response rate of 78% versus 29% (odds ratio, 10.42), and when those with nonmeasurable CNS disease were included in the intracranial response assessment, the odds ratio was 13.

Median intracranial PFS among those with CNS involvement at baseline was not reached in the brigatinib arm versus 5.6 months with crizotinib, for a highly statistically significant hazard ratio of 0.27. “Which, given that the median PFS for crizotinib in the overall population ... was 9.8 months, again emphasizes how CNS events in this subgroup tend to occur early,” he noted.

Study subjects had stage IIIB/IV ALK-positive non–small cell lung cancer (NSCLC) based on local ALK testing, Eastern Cooperative Oncology Group performance status of 0-2, no more than one prior systemic therapy for locally advanced/metastatic NSCLC, and no prior ALK inhibitor therapy, Dr. Camidge said, noting that asymptomatic, untreated brain metastases were allowed and crossover to the brigatinib arm was permitted for those with blinded independent review committee–assessed progression on crizotinib.

Those randomized to the brigatinib arm had a median age of 58 years and received 180 mg daily with a 7-day lead-in at 90 mg. Those randomized to the crizotinib group had a median age of 60 years and received 250 mg twice daily. Prior chemotherapy for advanced disease was received by 26% and 27% and brain metastasis was present in 29% and 30% of patients in the arms, respectively.

The most common treatment-emergent adverse events of grade 3 or higher in the brigatinib patients were laboratory abnormalities such as creatinine phosphokinase, lipase, and amylase increases, and the most common in the crizotinib group were gastrointestinal effects, transaminitis, bradycardia, peripheral edema, and vision disturbances.

Discontinuations caused by adverse events occurred in 12% and 9% of the brigatinib and crizotinib patients, respectively, he said. No clinical cases of pancreatitis occurred in either arm, there was no difference in the incidence of any grade myalgia or musculoskeletal pain between arms, and there was no grade 3 or greater myalgia or musculoskeletal pain reported.

Early-onset interstitial lung disease, however, “appears to be a unique side effect of brigatinib,” Dr. Camidge noted.

Although interstitial lung disease/pneumonitis occurred in both groups, onset at days 3-8 after treatment initiation occurred only with brigatinib, he said, adding that “it only occurred in 3% of cases – half the rate seen in the postcrizotinib setting.”

The PROFILE 1014 study established crizotinib as the standard first-line therapy for advanced ALK-rearranged NSCLC, showing superior PFS versus pemetrexed doublet chemotherapy (HR, 0.45), but median PFS with crizotinib in that trial was only 10.9 months, Dr. Camidge said.

The next-generation ALK inhibitor brigatinib, however, has demonstrated broad preclinical activity against ALK resistance mutations, has excellent CNS penetration, and is the only ALK inhibitor with marked activity against multiple epidermal growth factor receptor–mutant cell lines, he said. “It has already shown significant activity both within the CNS and extracranially in the postcrizotinib setting, where it has consistently demonstrated the longest reported median PFS [up to 16.7 months] of any licensed or experimental ALK inhibitor.”

The ALTA-1L study provides a head-to-head comparison of brigatinib and crizotinib in a real-world setting, and the findings demonstrate that “brigatinib represents a promising new treatment for inhibitor-naive, ALK-rearranged NSCLC,” he said.

In a press statement, Dr. Camidge further stated that, based on these findings, brigatinib is set to become a first-line treatment option for ALK-positive lung cancer, adding that, “even with only 9-11 months of follow-up, the efficacy of brigatinib is clearly superior to crizotinib. A lot of the initial difference is driven by an effect on brain metastases, which tend to be an earlier progression event. However, once differences in control of disease outside the brain have time to manifest, it is possible the PFS improvement may increase.”

Both Dr. Camidge and invited discussant Fiona Blackhall, PhD, noted that the tolerability of brigatinib may be “even better in the real world,” as most of the 29% of patients on the brigatinib arm with adverse event–related dose reductions had “paper toxicities” for which the clinical impact is not well understood.

The rate of dose reductions for adverse events with brigatinib was higher in ALTA-1L than that seen in earlier studies of the second-generation ALK inhibitor alectinib, said Dr. Blackhall, professor and chair in thoracic oncology at the University of Manchester (England).

“We need to be sure that these dose reductions are appropriate and not potentially compromising efficacy,” she added.

Dr. Blackhall also suggested that sequential use of crizotinib and other ALK inhibitors like brigatinib should be evaluated and that the potential impact of ALK inhibitor selection “on the spectrum and type of resistance mutations and mechanisms” should be considered.

“Brigatinib is a new first-line treatment option for patients with ALK-positive non–small cell lung cancer. ... But in the absence of direct comparison of next-generation ALK inhibitors, it is going to take some time before we can determine whether there is indeed – if there ever will be – a ‘best’ ALK inhibitor for our patients,” she said.

Dr. Camidge has received honoraria from Arrys/Kyn, AstraZeneca, Biothera, Celgene, Clovis Oncology, Daiichi Sankyo, G1 Therapeutics, Genoptix, Hansoh, Ignyta, Lycera, Mersana Therapeutics, Novartis, Orion, Revolution Medicines, Roche/Genentech, and Takeda, and has received research funding from ARIADTakeda. Dr. Blackhall reported research funding from Amgen, AstraZeneca, Novartis, and Pfizer, and has served has an advisory board member, consultant, or speaker for AbbVie, Boehringer Ingelheim, Cell Medica, Medivation, Merck, Regeneron, Roche, and Takeda.

[email protected]

SOURCE: Camidge DR et al. WCLC 2018, Abstract PL02.03.

TORONTO – Adding the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab to standard first-line chemotherapy and maintenance therapy in patients with advanced nonsquamous non–small-cell lung cancer significantly improved progression-free survival (PFS), in the randomized, open-label IMpower132 trial.

At a minimum follow-up of 11.7 months (median, 14.8 months), investigator-assessed median PFS in 292 patients enrolled in the atezolizumab arm of the global study was 7.6 months, compared with 5.2 months – a 40% reduction in risk of disease progression – in 286 patients who received only first-line carboplatin plus pemetrexed and pemetrexed maintenance therapy (hazard ratio, 0.60), Vassiliki A Papadimitrakopoulou, MD, reported at the World Conference on Lung Cancer.

“The landmark PFS at 12-months showed almost a doubling for the investigational arm [at] 33.7% vs. 17%,” said Dr. Papadimitrakopoulou, professor of medicine and chief of the section of thoracic medical oncology at MD Anderson Cancer Center in Houston. “PFS benefit was seen across all key subgroups, [and was] especially pronounced for female patients (HR, 0.51), Asian patients (HR, 0.42), never-smokers (HR, 0.49), and patients who didn’t have liver metastases (HR, 0.56).”

PFS was also looked at – as an exploratory endpoint – by PD-L1 status in biomarker-evaluable patients, and “again, benefit was seen across all PD-L1-defined subgroups with a consistent trend for most benefit among the highest expressers,” she noted.

Median PFS was 10.8 months in 25 atezolizumab-treated patients with high PD-L1 expression, vs. 6.5 months in 20 control group patients with high PD-L1 expression; 6.2 vs. 5.7 months in 63 and 73 patients with low-PD-L1 expression in the groups, respectively; and 8.5 vs. 4.9 months in 88 and 75 PD-L1-negative patients in the groups, respectively, she reported at the conference, which was sponsored by the International Association for the Study of Lung Cancer.

Interim analyses also showed a numerically superior improvement in median and 12-month overall survival in the atezolizumab vs. control group (median, 18.1 vs. 13.6 months; HR, 0.813; P = .0797; 12-month, 59.6% vs. 55.4%), she said, adding that overall survival will be looked at again at the final analysis of the data, which is anticipated some time in the first half of 2019.

Study participants were chemotherapy-naive patients with measurable stage IV nonsquamous NSCLC and Eastern Cooperative Oncology Group Performance Status 0-1. Those with tumors known to harbor epidermal growth factor receptor or anaplastic lymphoma kinase driver mutations were excluded, as were those with untreated central nervous system metastases, autoimmune disease, and prior exposure to immunotherapy.

All patients received four or six cycles of carboplatin at a dose of area under the curve 6 mg/mL/min or cisplatin at a dose of 75 mg/m² plus 500 mg/m² of pemetrexed every 3 weeks, and those in the experimental arm also received 1,200 mg of atezolizumab every 3 weeks. Maintenance therapy included pemetrexed alone in the control arm, and atezolizumab plus pemetrexed in the experimental arm.

Treatment was well tolerated, and no new safety signals emerged, Dr. Papadimitrakopoulou said, noting that adverse events were similar in the groups, but more common in the atezolizumab-treated patients. Grade 3-4 treatment-related adverse events occurred in 54% of patients receiving atezolizumab vs. 39% of those in the control group, and serious adverse events occurred in 33% vs. 16%.

“The findings from IMpower132 indicate that the addition of atezolizumab to a backbone of carboplatin and pemetrexed chemotherapy provides better clinical efficacy than carboplatin and pemetrexed alone,” Dr. Papadimitrakopoulou said in a press statement. “By inhibiting the interaction of PD-L1 with its receptors PD-1 and B7.1, atezolizumab restores tumor-specific T-cell immunity, offering a valuable treatment option that prolongs survival for patients with stage IV nonsquamous NSCLC.”

IMpower132 is sponsored by F. Hoffmann–La Roche Ltd. Dr. Papadimitrakopoulou has received research support from, and/or is an advisory board member for numerous companies including F. Hoffmann–La Roche.

SOURCE: Papadimitrakopoulou V et al. WCLC 2018 Abstract OA05.07.

TORONTO – Adding the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab to standard first-line chemotherapy and maintenance therapy in patients with advanced nonsquamous non–small-cell lung cancer significantly improved progression-free survival (PFS), in the randomized, open-label IMpower132 trial.

At a minimum follow-up of 11.7 months (median, 14.8 months), investigator-assessed median PFS in 292 patients enrolled in the atezolizumab arm of the global study was 7.6 months, compared with 5.2 months – a 40% reduction in risk of disease progression – in 286 patients who received only first-line carboplatin plus pemetrexed and pemetrexed maintenance therapy (hazard ratio, 0.60), Vassiliki A Papadimitrakopoulou, MD, reported at the World Conference on Lung Cancer.

“The landmark PFS at 12-months showed almost a doubling for the investigational arm [at] 33.7% vs. 17%,” said Dr. Papadimitrakopoulou, professor of medicine and chief of the section of thoracic medical oncology at MD Anderson Cancer Center in Houston. “PFS benefit was seen across all key subgroups, [and was] especially pronounced for female patients (HR, 0.51), Asian patients (HR, 0.42), never-smokers (HR, 0.49), and patients who didn’t have liver metastases (HR, 0.56).”

PFS was also looked at – as an exploratory endpoint – by PD-L1 status in biomarker-evaluable patients, and “again, benefit was seen across all PD-L1-defined subgroups with a consistent trend for most benefit among the highest expressers,” she noted.

Median PFS was 10.8 months in 25 atezolizumab-treated patients with high PD-L1 expression, vs. 6.5 months in 20 control group patients with high PD-L1 expression; 6.2 vs. 5.7 months in 63 and 73 patients with low-PD-L1 expression in the groups, respectively; and 8.5 vs. 4.9 months in 88 and 75 PD-L1-negative patients in the groups, respectively, she reported at the conference, which was sponsored by the International Association for the Study of Lung Cancer.

Interim analyses also showed a numerically superior improvement in median and 12-month overall survival in the atezolizumab vs. control group (median, 18.1 vs. 13.6 months; HR, 0.813; P = .0797; 12-month, 59.6% vs. 55.4%), she said, adding that overall survival will be looked at again at the final analysis of the data, which is anticipated some time in the first half of 2019.

Study participants were chemotherapy-naive patients with measurable stage IV nonsquamous NSCLC and Eastern Cooperative Oncology Group Performance Status 0-1. Those with tumors known to harbor epidermal growth factor receptor or anaplastic lymphoma kinase driver mutations were excluded, as were those with untreated central nervous system metastases, autoimmune disease, and prior exposure to immunotherapy.

All patients received four or six cycles of carboplatin at a dose of area under the curve 6 mg/mL/min or cisplatin at a dose of 75 mg/m² plus 500 mg/m² of pemetrexed every 3 weeks, and those in the experimental arm also received 1,200 mg of atezolizumab every 3 weeks. Maintenance therapy included pemetrexed alone in the control arm, and atezolizumab plus pemetrexed in the experimental arm.

Treatment was well tolerated, and no new safety signals emerged, Dr. Papadimitrakopoulou said, noting that adverse events were similar in the groups, but more common in the atezolizumab-treated patients. Grade 3-4 treatment-related adverse events occurred in 54% of patients receiving atezolizumab vs. 39% of those in the control group, and serious adverse events occurred in 33% vs. 16%.

“The findings from IMpower132 indicate that the addition of atezolizumab to a backbone of carboplatin and pemetrexed chemotherapy provides better clinical efficacy than carboplatin and pemetrexed alone,” Dr. Papadimitrakopoulou said in a press statement. “By inhibiting the interaction of PD-L1 with its receptors PD-1 and B7.1, atezolizumab restores tumor-specific T-cell immunity, offering a valuable treatment option that prolongs survival for patients with stage IV nonsquamous NSCLC.”

IMpower132 is sponsored by F. Hoffmann–La Roche Ltd. Dr. Papadimitrakopoulou has received research support from, and/or is an advisory board member for numerous companies including F. Hoffmann–La Roche.

SOURCE: Papadimitrakopoulou V et al. WCLC 2018 Abstract OA05.07.

TORONTO – Adding the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab to standard first-line chemotherapy and maintenance therapy in patients with advanced nonsquamous non–small-cell lung cancer significantly improved progression-free survival (PFS), in the randomized, open-label IMpower132 trial.

At a minimum follow-up of 11.7 months (median, 14.8 months), investigator-assessed median PFS in 292 patients enrolled in the atezolizumab arm of the global study was 7.6 months, compared with 5.2 months – a 40% reduction in risk of disease progression – in 286 patients who received only first-line carboplatin plus pemetrexed and pemetrexed maintenance therapy (hazard ratio, 0.60), Vassiliki A Papadimitrakopoulou, MD, reported at the World Conference on Lung Cancer.

“The landmark PFS at 12-months showed almost a doubling for the investigational arm [at] 33.7% vs. 17%,” said Dr. Papadimitrakopoulou, professor of medicine and chief of the section of thoracic medical oncology at MD Anderson Cancer Center in Houston. “PFS benefit was seen across all key subgroups, [and was] especially pronounced for female patients (HR, 0.51), Asian patients (HR, 0.42), never-smokers (HR, 0.49), and patients who didn’t have liver metastases (HR, 0.56).”

PFS was also looked at – as an exploratory endpoint – by PD-L1 status in biomarker-evaluable patients, and “again, benefit was seen across all PD-L1-defined subgroups with a consistent trend for most benefit among the highest expressers,” she noted.

Median PFS was 10.8 months in 25 atezolizumab-treated patients with high PD-L1 expression, vs. 6.5 months in 20 control group patients with high PD-L1 expression; 6.2 vs. 5.7 months in 63 and 73 patients with low-PD-L1 expression in the groups, respectively; and 8.5 vs. 4.9 months in 88 and 75 PD-L1-negative patients in the groups, respectively, she reported at the conference, which was sponsored by the International Association for the Study of Lung Cancer.

Interim analyses also showed a numerically superior improvement in median and 12-month overall survival in the atezolizumab vs. control group (median, 18.1 vs. 13.6 months; HR, 0.813; P = .0797; 12-month, 59.6% vs. 55.4%), she said, adding that overall survival will be looked at again at the final analysis of the data, which is anticipated some time in the first half of 2019.

Study participants were chemotherapy-naive patients with measurable stage IV nonsquamous NSCLC and Eastern Cooperative Oncology Group Performance Status 0-1. Those with tumors known to harbor epidermal growth factor receptor or anaplastic lymphoma kinase driver mutations were excluded, as were those with untreated central nervous system metastases, autoimmune disease, and prior exposure to immunotherapy.

All patients received four or six cycles of carboplatin at a dose of area under the curve 6 mg/mL/min or cisplatin at a dose of 75 mg/m² plus 500 mg/m² of pemetrexed every 3 weeks, and those in the experimental arm also received 1,200 mg of atezolizumab every 3 weeks. Maintenance therapy included pemetrexed alone in the control arm, and atezolizumab plus pemetrexed in the experimental arm.

Treatment was well tolerated, and no new safety signals emerged, Dr. Papadimitrakopoulou said, noting that adverse events were similar in the groups, but more common in the atezolizumab-treated patients. Grade 3-4 treatment-related adverse events occurred in 54% of patients receiving atezolizumab vs. 39% of those in the control group, and serious adverse events occurred in 33% vs. 16%.

“The findings from IMpower132 indicate that the addition of atezolizumab to a backbone of carboplatin and pemetrexed chemotherapy provides better clinical efficacy than carboplatin and pemetrexed alone,” Dr. Papadimitrakopoulou said in a press statement. “By inhibiting the interaction of PD-L1 with its receptors PD-1 and B7.1, atezolizumab restores tumor-specific T-cell immunity, offering a valuable treatment option that prolongs survival for patients with stage IV nonsquamous NSCLC.”

IMpower132 is sponsored by F. Hoffmann–La Roche Ltd. Dr. Papadimitrakopoulou has received research support from, and/or is an advisory board member for numerous companies including F. Hoffmann–La Roche.

SOURCE: Papadimitrakopoulou V et al. WCLC 2018 Abstract OA05.07.

TORONTO – Adding the humanized monoclonal programmed death-ligand 1 (PD-L1) antibody atezolizumab to standard first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) significantly improved overall and progression-free survival in the phase 1/3 IMpower133 trial.

Sharon Worcester/MDedge News

The combination may represent a new standard-of-care regimen for patients with untreated ES-SCLC, which is highly lethal – with 5-year survival of about 1%-3% – and represents about 13% of all lung cancers, Stephen V. Liu, MD, reported at the World Conference on Lung Cancer.

The findings were published simultaneously in the New England Journal of Medicine.

The median overall survival in 201 patients randomized to receive atezolizumab in addition to carboplatin and etoposide was 12.3 months, compared with 10.3 months in 202 patients who received placebo plus carboplatin and etoposide (hazard ratio, 0.7), Dr. Liu of Georgetown University, Washington, and a member of the trial steering committee said at the meeting, sponsored by the International Association for the Study of Lung Cancer.

“That translates to a 30% reduction in the risk of patient death,” he said at a press briefing during the conference. “Patients receiving atezolizumab had a much greater likelihood of being alive at 1 year, with a 1-year survival rate of 51.7% versus 38.2%.”

Median progression-free survival(PFS) also improved with atezolizumab (5.2 months vs. 4.3 months with placebo; HR, 0.77), as did 6-month PFS. At 12 months there was more than a doubling of PFS in the atezolizumab group (5.0% vs. 12.6%), he said.

Participants in the double-blind trial were treatment-naive all-comers with measurable ES-SCLC and good performance status. They received four 21-day cycles of intravenous carboplatin (area under the curve, 5 mg/mL per minute) on day 1 plus intravenous etoposide (100 mg/m²) on days 1-3 with either concurrent 1,200 mg of atezolizumab on day 1 or placebo, followed by maintenance therapy with atezolizumab or placebo until intolerable toxicity or disease progression.

The treatment benefits were seen across many patient subgroups and regardless of tumor mutational burden.

The atezolizumab safety profile was as expected with no new safety signals and did not compromise patients’ ability to complete four treatment cycles, Dr. Liu noted.

The findings are exciting in that they represent the first in decades to show a significant improvement in survival in patients with ES-SCLC, he said. Although most patients have an initial response to standard-of-care chemotherapy, that response isn’t durable. “As much as we expect a response, we also know that it’s transient; we expect a response, we expect relapse. There hasn’t been a change really in the past 20 years, at least, with this regimen that we’ve been using since the 1980s.”

That’s not for lack of trying, he added, noting that more than 40 phase 3 studies have looked at more than 60 different drugs since the 1970s and have “failed to move the needle.”

Immunotherapy, however, has dramatically improved the therapeutic landscape in non–small cell lung cancer, and preclinical data and clinical experience suggest “a possible synergy between checkpoint inhibition and chemotherapy,” which led to this global study, he explained.

“This is the first study in over 20 years to show a significant improvement in survival and progression-free survival in initial treatment of small cell lung cancer. The concurrent administration of atezolizumab with chemotherapy helped people live longer, compared to chemotherapy alone,” Dr. Liu concluded, adding in a press statement that “this is an exciting time in oncology, and we are thrilled to finally see real progress in the SCLC space.”

When questioned about the role of PD-L1 in this population and the possibility of identifying a subgroup in which this treatment may be more cost effective, he noted that tissue samples weren’t required at enrollment in this study, but were collected from some patients, and future analyses will assess those samples to try to determine if there are subsets of patients who derive particular benefit from immunotherapy in this setting.

“But today, in an all-comer population, this combination has improved survival,” he said.

IMpower133 was sponsored by F. Hoffman–La Roche. Dr. Liu is a speaker or advisory board member for Genentech, Pfizer, Takeda, Celgene, Eli Lilly, Taiho Pharmaceutical, Bristol-Myers Squibb, AstraZeneca, and Ignyta, and has received research or grant support from Genentech, Pfizer, Threshold Pharmaceuticals, Clovis Oncology, Corvus Pharmaceuticals, Esanex, Bayer, OncoMed Pharmaceuticals, Ignyta, Merck, Lycera, AstraZeneca, and Molecular Partners.

SOURCE: Liu SV et al. WCLC 2018, Abstract PL02.07.

TORONTO – Adding the humanized monoclonal programmed death-ligand 1 (PD-L1) antibody atezolizumab to standard first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) significantly improved overall and progression-free survival in the phase 1/3 IMpower133 trial.

Sharon Worcester/MDedge News

The combination may represent a new standard-of-care regimen for patients with untreated ES-SCLC, which is highly lethal – with 5-year survival of about 1%-3% – and represents about 13% of all lung cancers, Stephen V. Liu, MD, reported at the World Conference on Lung Cancer.

The findings were published simultaneously in the New England Journal of Medicine.

The median overall survival in 201 patients randomized to receive atezolizumab in addition to carboplatin and etoposide was 12.3 months, compared with 10.3 months in 202 patients who received placebo plus carboplatin and etoposide (hazard ratio, 0.7), Dr. Liu of Georgetown University, Washington, and a member of the trial steering committee said at the meeting, sponsored by the International Association for the Study of Lung Cancer.

“That translates to a 30% reduction in the risk of patient death,” he said at a press briefing during the conference. “Patients receiving atezolizumab had a much greater likelihood of being alive at 1 year, with a 1-year survival rate of 51.7% versus 38.2%.”

Median progression-free survival(PFS) also improved with atezolizumab (5.2 months vs. 4.3 months with placebo; HR, 0.77), as did 6-month PFS. At 12 months there was more than a doubling of PFS in the atezolizumab group (5.0% vs. 12.6%), he said.

Participants in the double-blind trial were treatment-naive all-comers with measurable ES-SCLC and good performance status. They received four 21-day cycles of intravenous carboplatin (area under the curve, 5 mg/mL per minute) on day 1 plus intravenous etoposide (100 mg/m²) on days 1-3 with either concurrent 1,200 mg of atezolizumab on day 1 or placebo, followed by maintenance therapy with atezolizumab or placebo until intolerable toxicity or disease progression.

The treatment benefits were seen across many patient subgroups and regardless of tumor mutational burden.

The atezolizumab safety profile was as expected with no new safety signals and did not compromise patients’ ability to complete four treatment cycles, Dr. Liu noted.

The findings are exciting in that they represent the first in decades to show a significant improvement in survival in patients with ES-SCLC, he said. Although most patients have an initial response to standard-of-care chemotherapy, that response isn’t durable. “As much as we expect a response, we also know that it’s transient; we expect a response, we expect relapse. There hasn’t been a change really in the past 20 years, at least, with this regimen that we’ve been using since the 1980s.”

That’s not for lack of trying, he added, noting that more than 40 phase 3 studies have looked at more than 60 different drugs since the 1970s and have “failed to move the needle.”

Immunotherapy, however, has dramatically improved the therapeutic landscape in non–small cell lung cancer, and preclinical data and clinical experience suggest “a possible synergy between checkpoint inhibition and chemotherapy,” which led to this global study, he explained.

“This is the first study in over 20 years to show a significant improvement in survival and progression-free survival in initial treatment of small cell lung cancer. The concurrent administration of atezolizumab with chemotherapy helped people live longer, compared to chemotherapy alone,” Dr. Liu concluded, adding in a press statement that “this is an exciting time in oncology, and we are thrilled to finally see real progress in the SCLC space.”

When questioned about the role of PD-L1 in this population and the possibility of identifying a subgroup in which this treatment may be more cost effective, he noted that tissue samples weren’t required at enrollment in this study, but were collected from some patients, and future analyses will assess those samples to try to determine if there are subsets of patients who derive particular benefit from immunotherapy in this setting.

“But today, in an all-comer population, this combination has improved survival,” he said.

IMpower133 was sponsored by F. Hoffman–La Roche. Dr. Liu is a speaker or advisory board member for Genentech, Pfizer, Takeda, Celgene, Eli Lilly, Taiho Pharmaceutical, Bristol-Myers Squibb, AstraZeneca, and Ignyta, and has received research or grant support from Genentech, Pfizer, Threshold Pharmaceuticals, Clovis Oncology, Corvus Pharmaceuticals, Esanex, Bayer, OncoMed Pharmaceuticals, Ignyta, Merck, Lycera, AstraZeneca, and Molecular Partners.

SOURCE: Liu SV et al. WCLC 2018, Abstract PL02.07.

TORONTO – Adding the humanized monoclonal programmed death-ligand 1 (PD-L1) antibody atezolizumab to standard first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) significantly improved overall and progression-free survival in the phase 1/3 IMpower133 trial.

Sharon Worcester/MDedge News

The combination may represent a new standard-of-care regimen for patients with untreated ES-SCLC, which is highly lethal – with 5-year survival of about 1%-3% – and represents about 13% of all lung cancers, Stephen V. Liu, MD, reported at the World Conference on Lung Cancer.

The findings were published simultaneously in the New England Journal of Medicine.

The median overall survival in 201 patients randomized to receive atezolizumab in addition to carboplatin and etoposide was 12.3 months, compared with 10.3 months in 202 patients who received placebo plus carboplatin and etoposide (hazard ratio, 0.7), Dr. Liu of Georgetown University, Washington, and a member of the trial steering committee said at the meeting, sponsored by the International Association for the Study of Lung Cancer.

“That translates to a 30% reduction in the risk of patient death,” he said at a press briefing during the conference. “Patients receiving atezolizumab had a much greater likelihood of being alive at 1 year, with a 1-year survival rate of 51.7% versus 38.2%.”

Median progression-free survival(PFS) also improved with atezolizumab (5.2 months vs. 4.3 months with placebo; HR, 0.77), as did 6-month PFS. At 12 months there was more than a doubling of PFS in the atezolizumab group (5.0% vs. 12.6%), he said.

Participants in the double-blind trial were treatment-naive all-comers with measurable ES-SCLC and good performance status. They received four 21-day cycles of intravenous carboplatin (area under the curve, 5 mg/mL per minute) on day 1 plus intravenous etoposide (100 mg/m²) on days 1-3 with either concurrent 1,200 mg of atezolizumab on day 1 or placebo, followed by maintenance therapy with atezolizumab or placebo until intolerable toxicity or disease progression.

The treatment benefits were seen across many patient subgroups and regardless of tumor mutational burden.

The atezolizumab safety profile was as expected with no new safety signals and did not compromise patients’ ability to complete four treatment cycles, Dr. Liu noted.

The findings are exciting in that they represent the first in decades to show a significant improvement in survival in patients with ES-SCLC, he said. Although most patients have an initial response to standard-of-care chemotherapy, that response isn’t durable. “As much as we expect a response, we also know that it’s transient; we expect a response, we expect relapse. There hasn’t been a change really in the past 20 years, at least, with this regimen that we’ve been using since the 1980s.”

That’s not for lack of trying, he added, noting that more than 40 phase 3 studies have looked at more than 60 different drugs since the 1970s and have “failed to move the needle.”

Immunotherapy, however, has dramatically improved the therapeutic landscape in non–small cell lung cancer, and preclinical data and clinical experience suggest “a possible synergy between checkpoint inhibition and chemotherapy,” which led to this global study, he explained.

“This is the first study in over 20 years to show a significant improvement in survival and progression-free survival in initial treatment of small cell lung cancer. The concurrent administration of atezolizumab with chemotherapy helped people live longer, compared to chemotherapy alone,” Dr. Liu concluded, adding in a press statement that “this is an exciting time in oncology, and we are thrilled to finally see real progress in the SCLC space.”

When questioned about the role of PD-L1 in this population and the possibility of identifying a subgroup in which this treatment may be more cost effective, he noted that tissue samples weren’t required at enrollment in this study, but were collected from some patients, and future analyses will assess those samples to try to determine if there are subsets of patients who derive particular benefit from immunotherapy in this setting.

“But today, in an all-comer population, this combination has improved survival,” he said.

IMpower133 was sponsored by F. Hoffman–La Roche. Dr. Liu is a speaker or advisory board member for Genentech, Pfizer, Takeda, Celgene, Eli Lilly, Taiho Pharmaceutical, Bristol-Myers Squibb, AstraZeneca, and Ignyta, and has received research or grant support from Genentech, Pfizer, Threshold Pharmaceuticals, Clovis Oncology, Corvus Pharmaceuticals, Esanex, Bayer, OncoMed Pharmaceuticals, Ignyta, Merck, Lycera, AstraZeneca, and Molecular Partners.

SOURCE: Liu SV et al. WCLC 2018, Abstract PL02.07.

TORONTO – The programmed death-ligand 1 (PD-L1) inhibitor durvalumab significantly improves overall survival in patients with stage III unresectable non–small-cell lung cancer without progression after chemoradiotherapy, according to updated results from the global phase 3 PACIFIC study.

Sharon Worcester/MDedge News

The findings, presented at the World Conference on Lung Cancer, follow a prior report from the study showing improved progression-free survival (PFS) in durvalumab-treated patients (stratified hazard ratio, 0.52), and together these survival benefits mark the first major advance in this disease setting in decades,” Scott J. Antonia, MD, reported at the conference, sponsored by the International Association for the Study of Lung Cancer (IASLC).

“The fact is this is a new standard of care treatment for the patients with this disease,” he said, adding that “in all likelihood we are improving the cure rate for the patients with this disease.”

The findings were published simultaneously in the New England Journal of Medicine.

Overall survival at a median follow-up of 25.2 months in 473 patients randomized to receive durvalumab was significantly greater than among 236 who received placebo (stratified HR, 0.68; median survival not reached vs. 28.7 months in the groups, respectively), said Dr. Antonia of the H. Lee Moffitt Cancer Center and Research Institute, and professor of oncologic sciences at the University of South Florida, Tampa.

Durvalumab also improved overall survival in all prespecified subgroups, and PFS was similar to that in previous reports (stratified HR 0.51; median of 17.2 vs. 5.6 months with durvalumab and placebo, respectively), he said, noting that “interestingly, patients who were nonsmokers did benefit from durvalumab.”

This is notable because prior research suggests that never-smokers with advanced stage cancer have less of a chance of responding to immunotherapy (although they should still be offered immunotherapy), he explained.

“Also interestingly, it appears as if cisplatin was the better drug to use in the conventional therapy portion of the treatment,” he said.

Durvalumab also provided continued improvement vs. placebo in time to death or distant metastasis (stratified HR, 0.53), time to second progression (stratified HR, 0.58), time to first subsequent therapy or death (stratified HR, 0.58), and time to second subsequent therapy or death (stratified HR, 0.63).

Study subjects were patients with World Health Organization Performance Status scores of 0 or 1 with any PD-L1 tumor status, who received at least two cycles of conventional standard-of-care platinum-based chemoradiotherapy (CRT). They were randomized between May 2014 and April 2016 – at 1-42 days after CRT – to receive intravenous durvalumab at a dose of 10 mg/kg given intravenously every 2 weeks or placebo, and were stratified by age, gender, and smoking history.

Durvalumab was well tolerated; 30.5% and 26.1% of treatment and placebo patients, respectively, had grade 3/4 adverse events, and 15.4% and 9.8%, respectively, discontinued because of adverse events.

“There were no new safety signals with this longer follow-up,” Dr. Antonia said.

After study treatment ended, 41% and 54% in the groups, respectively, received additional anticancer therapy, and 8% and 22.4%, respectively, received additional immunotherapy, he noted.

The results are not only statistically significant, but clinically meaningful, and they offer new hope for patients with a disease that, in those who receive chemoradiotherapy, has a 3-year survival rate of only about 27%, he said.

During a press briefing at the conference, moderator Frances Shepherd, MD, a medical oncologist at Princess Margaret Cancer Centre in Toronto and a past president of the International Association for the Study of Lung Cancer, called the results “very exciting” given that this type of cancer represents about a third of all lung cancers and therefore affects an “enormous number of patients in Canada and globally.”

Sharon Worcester/MDedge News

SOURCE: Antonia S et al., WCLC 2018 Abstract PL02.01.

TORONTO – The programmed death-ligand 1 (PD-L1) inhibitor durvalumab significantly improves overall survival in patients with stage III unresectable non–small-cell lung cancer without progression after chemoradiotherapy, according to updated results from the global phase 3 PACIFIC study.

Sharon Worcester/MDedge News

The findings, presented at the World Conference on Lung Cancer, follow a prior report from the study showing improved progression-free survival (PFS) in durvalumab-treated patients (stratified hazard ratio, 0.52), and together these survival benefits mark the first major advance in this disease setting in decades,” Scott J. Antonia, MD, reported at the conference, sponsored by the International Association for the Study of Lung Cancer (IASLC).

“The fact is this is a new standard of care treatment for the patients with this disease,” he said, adding that “in all likelihood we are improving the cure rate for the patients with this disease.”

The findings were published simultaneously in the New England Journal of Medicine.

Overall survival at a median follow-up of 25.2 months in 473 patients randomized to receive durvalumab was significantly greater than among 236 who received placebo (stratified HR, 0.68; median survival not reached vs. 28.7 months in the groups, respectively), said Dr. Antonia of the H. Lee Moffitt Cancer Center and Research Institute, and professor of oncologic sciences at the University of South Florida, Tampa.

Durvalumab also improved overall survival in all prespecified subgroups, and PFS was similar to that in previous reports (stratified HR 0.51; median of 17.2 vs. 5.6 months with durvalumab and placebo, respectively), he said, noting that “interestingly, patients who were nonsmokers did benefit from durvalumab.”

This is notable because prior research suggests that never-smokers with advanced stage cancer have less of a chance of responding to immunotherapy (although they should still be offered immunotherapy), he explained.

“Also interestingly, it appears as if cisplatin was the better drug to use in the conventional therapy portion of the treatment,” he said.

Durvalumab also provided continued improvement vs. placebo in time to death or distant metastasis (stratified HR, 0.53), time to second progression (stratified HR, 0.58), time to first subsequent therapy or death (stratified HR, 0.58), and time to second subsequent therapy or death (stratified HR, 0.63).

Study subjects were patients with World Health Organization Performance Status scores of 0 or 1 with any PD-L1 tumor status, who received at least two cycles of conventional standard-of-care platinum-based chemoradiotherapy (CRT). They were randomized between May 2014 and April 2016 – at 1-42 days after CRT – to receive intravenous durvalumab at a dose of 10 mg/kg given intravenously every 2 weeks or placebo, and were stratified by age, gender, and smoking history.

Durvalumab was well tolerated; 30.5% and 26.1% of treatment and placebo patients, respectively, had grade 3/4 adverse events, and 15.4% and 9.8%, respectively, discontinued because of adverse events.

“There were no new safety signals with this longer follow-up,” Dr. Antonia said.

After study treatment ended, 41% and 54% in the groups, respectively, received additional anticancer therapy, and 8% and 22.4%, respectively, received additional immunotherapy, he noted.

The results are not only statistically significant, but clinically meaningful, and they offer new hope for patients with a disease that, in those who receive chemoradiotherapy, has a 3-year survival rate of only about 27%, he said.

During a press briefing at the conference, moderator Frances Shepherd, MD, a medical oncologist at Princess Margaret Cancer Centre in Toronto and a past president of the International Association for the Study of Lung Cancer, called the results “very exciting” given that this type of cancer represents about a third of all lung cancers and therefore affects an “enormous number of patients in Canada and globally.”

Sharon Worcester/MDedge News

SOURCE: Antonia S et al., WCLC 2018 Abstract PL02.01.

TORONTO – The programmed death-ligand 1 (PD-L1) inhibitor durvalumab significantly improves overall survival in patients with stage III unresectable non–small-cell lung cancer without progression after chemoradiotherapy, according to updated results from the global phase 3 PACIFIC study.

Sharon Worcester/MDedge News

The findings, presented at the World Conference on Lung Cancer, follow a prior report from the study showing improved progression-free survival (PFS) in durvalumab-treated patients (stratified hazard ratio, 0.52), and together these survival benefits mark the first major advance in this disease setting in decades,” Scott J. Antonia, MD, reported at the conference, sponsored by the International Association for the Study of Lung Cancer (IASLC).

“The fact is this is a new standard of care treatment for the patients with this disease,” he said, adding that “in all likelihood we are improving the cure rate for the patients with this disease.”

The findings were published simultaneously in the New England Journal of Medicine.

Overall survival at a median follow-up of 25.2 months in 473 patients randomized to receive durvalumab was significantly greater than among 236 who received placebo (stratified HR, 0.68; median survival not reached vs. 28.7 months in the groups, respectively), said Dr. Antonia of the H. Lee Moffitt Cancer Center and Research Institute, and professor of oncologic sciences at the University of South Florida, Tampa.

Durvalumab also improved overall survival in all prespecified subgroups, and PFS was similar to that in previous reports (stratified HR 0.51; median of 17.2 vs. 5.6 months with durvalumab and placebo, respectively), he said, noting that “interestingly, patients who were nonsmokers did benefit from durvalumab.”

This is notable because prior research suggests that never-smokers with advanced stage cancer have less of a chance of responding to immunotherapy (although they should still be offered immunotherapy), he explained.

“Also interestingly, it appears as if cisplatin was the better drug to use in the conventional therapy portion of the treatment,” he said.

Durvalumab also provided continued improvement vs. placebo in time to death or distant metastasis (stratified HR, 0.53), time to second progression (stratified HR, 0.58), time to first subsequent therapy or death (stratified HR, 0.58), and time to second subsequent therapy or death (stratified HR, 0.63).

Study subjects were patients with World Health Organization Performance Status scores of 0 or 1 with any PD-L1 tumor status, who received at least two cycles of conventional standard-of-care platinum-based chemoradiotherapy (CRT). They were randomized between May 2014 and April 2016 – at 1-42 days after CRT – to receive intravenous durvalumab at a dose of 10 mg/kg given intravenously every 2 weeks or placebo, and were stratified by age, gender, and smoking history.

Durvalumab was well tolerated; 30.5% and 26.1% of treatment and placebo patients, respectively, had grade 3/4 adverse events, and 15.4% and 9.8%, respectively, discontinued because of adverse events.

“There were no new safety signals with this longer follow-up,” Dr. Antonia said.

After study treatment ended, 41% and 54% in the groups, respectively, received additional anticancer therapy, and 8% and 22.4%, respectively, received additional immunotherapy, he noted.

The results are not only statistically significant, but clinically meaningful, and they offer new hope for patients with a disease that, in those who receive chemoradiotherapy, has a 3-year survival rate of only about 27%, he said.

During a press briefing at the conference, moderator Frances Shepherd, MD, a medical oncologist at Princess Margaret Cancer Centre in Toronto and a past president of the International Association for the Study of Lung Cancer, called the results “very exciting” given that this type of cancer represents about a third of all lung cancers and therefore affects an “enormous number of patients in Canada and globally.”

Sharon Worcester/MDedge News

SOURCE: Antonia S et al., WCLC 2018 Abstract PL02.01.

TORONTO – Computed tomography screening among asymptomatic men at high risk for lung cancer reduced lung cancer deaths by a highly statistically significant 26% at 10 years and appeared to reduce lung cancer mortality risk even more in women in the population-based, NELSON trial.

Sharon Worcester/MDedge News

The findings from this large controlled trial encompassing more than 27,000 CT scans in 15,792 individuals support those from the National Lung Screening Trials (NLST), published in 2011, and should “inform and direct future CT screening programs worldwide,” according to Harry de Koning, MD, who presented the findings at the World Conference on Lung Cancer.

Participants were randomized to CT screening at baseline, 1, 3, and 5.5 years after randomization, or to a control group that received usual care. Overall 157 lung cancer deaths occurred in the screening arm vs. 250 in the control arm. Detection rates varied between 0.8% and 1.1% across screenings (0.9% overall), and the positive predictive value of screening was 41%, Dr. de Koning of Erasmus Medical Center, Rotterdam, the Netherlands, said at the meeting sponsored by the International Association for the Study of Lung Cancer.

Notably, 69% of the 243 lung cancers detected by screening were detected at stage 1A or 1B, compared with 10%-12% being detected at stage 4 in about 50% of control patients and based on registry data in the Netherlands.

“There’s huge importance of this early detection in the screening arm,” Dr. de Koning said.

Additionally, an analysis of a subset of those with lung cancer showed a significant threefold increase in surgical treatment among the screened patients vs. those in the control arm who developed lung cancer (67.7% vs. 24.5%), he said.

CT screening reduced the risk of death from lung cancer by 9% to 41% in men over the course of the study, with an overall reduction of 26% at 10 years, and in a smaller subset of women, the rate-ratio of dying from lung cancer varied from 0.39 to 0.61 at different years of follow-up, he said, noting that this suggests a “significant and even larger reduction” in women.

Study participants were individuals aged 50-74 years in the Netherlands and Leuven, Belgium, who were considered at high risk for lung cancer based on responses to a general questionnaire. Participants’ records were linked with national registries with 100% coverage regarding cancer diagnosis and date and cause of death, and medical records for deceased lung cancer patients were reviewed by a blinded expert panel through 2013, and for the remaining study years cause of death as reported by Statistics Netherlands was used. Compliance among those randomized to the screening group was 86%, Dr. de Koning said.

“These findings show that CT screenings are an effective way to assess lung nodules in people at high risk for lung cancer, often leading to detection of suspicious nodules and subsequent surgical intervention at relatively low rates and with few false positives, and can positively increase the chances of cure in this devastating disease,” Dr. de Koning said in a press statement. “It is the second-largest trial in the world, with an even more favorable outcome than the first trial, the NLST, showed. These results should be used to inform and direct future CT screening in the world.”

During a press briefing, in response to a question about whether lung cancer screening should be offered more widely, he said that yes, countries – including the United States – should take note that “now two large-scale trials show large benefit.”

Dr. de Koning reported having no disclosures.

[email protected]

TORONTO – Computed tomography screening among asymptomatic men at high risk for lung cancer reduced lung cancer deaths by a highly statistically significant 26% at 10 years and appeared to reduce lung cancer mortality risk even more in women in the population-based, NELSON trial.

Sharon Worcester/MDedge News

The findings from this large controlled trial encompassing more than 27,000 CT scans in 15,792 individuals support those from the National Lung Screening Trials (NLST), published in 2011, and should “inform and direct future CT screening programs worldwide,” according to Harry de Koning, MD, who presented the findings at the World Conference on Lung Cancer.

Participants were randomized to CT screening at baseline, 1, 3, and 5.5 years after randomization, or to a control group that received usual care. Overall 157 lung cancer deaths occurred in the screening arm vs. 250 in the control arm. Detection rates varied between 0.8% and 1.1% across screenings (0.9% overall), and the positive predictive value of screening was 41%, Dr. de Koning of Erasmus Medical Center, Rotterdam, the Netherlands, said at the meeting sponsored by the International Association for the Study of Lung Cancer.

Notably, 69% of the 243 lung cancers detected by screening were detected at stage 1A or 1B, compared with 10%-12% being detected at stage 4 in about 50% of control patients and based on registry data in the Netherlands.

“There’s huge importance of this early detection in the screening arm,” Dr. de Koning said.

Additionally, an analysis of a subset of those with lung cancer showed a significant threefold increase in surgical treatment among the screened patients vs. those in the control arm who developed lung cancer (67.7% vs. 24.5%), he said.

CT screening reduced the risk of death from lung cancer by 9% to 41% in men over the course of the study, with an overall reduction of 26% at 10 years, and in a smaller subset of women, the rate-ratio of dying from lung cancer varied from 0.39 to 0.61 at different years of follow-up, he said, noting that this suggests a “significant and even larger reduction” in women.

Study participants were individuals aged 50-74 years in the Netherlands and Leuven, Belgium, who were considered at high risk for lung cancer based on responses to a general questionnaire. Participants’ records were linked with national registries with 100% coverage regarding cancer diagnosis and date and cause of death, and medical records for deceased lung cancer patients were reviewed by a blinded expert panel through 2013, and for the remaining study years cause of death as reported by Statistics Netherlands was used. Compliance among those randomized to the screening group was 86%, Dr. de Koning said.

“These findings show that CT screenings are an effective way to assess lung nodules in people at high risk for lung cancer, often leading to detection of suspicious nodules and subsequent surgical intervention at relatively low rates and with few false positives, and can positively increase the chances of cure in this devastating disease,” Dr. de Koning said in a press statement. “It is the second-largest trial in the world, with an even more favorable outcome than the first trial, the NLST, showed. These results should be used to inform and direct future CT screening in the world.”

During a press briefing, in response to a question about whether lung cancer screening should be offered more widely, he said that yes, countries – including the United States – should take note that “now two large-scale trials show large benefit.”

Dr. de Koning reported having no disclosures.

[email protected]

TORONTO – Computed tomography screening among asymptomatic men at high risk for lung cancer reduced lung cancer deaths by a highly statistically significant 26% at 10 years and appeared to reduce lung cancer mortality risk even more in women in the population-based, NELSON trial.

Sharon Worcester/MDedge News

The findings from this large controlled trial encompassing more than 27,000 CT scans in 15,792 individuals support those from the National Lung Screening Trials (NLST), published in 2011, and should “inform and direct future CT screening programs worldwide,” according to Harry de Koning, MD, who presented the findings at the World Conference on Lung Cancer.

Participants were randomized to CT screening at baseline, 1, 3, and 5.5 years after randomization, or to a control group that received usual care. Overall 157 lung cancer deaths occurred in the screening arm vs. 250 in the control arm. Detection rates varied between 0.8% and 1.1% across screenings (0.9% overall), and the positive predictive value of screening was 41%, Dr. de Koning of Erasmus Medical Center, Rotterdam, the Netherlands, said at the meeting sponsored by the International Association for the Study of Lung Cancer.

Notably, 69% of the 243 lung cancers detected by screening were detected at stage 1A or 1B, compared with 10%-12% being detected at stage 4 in about 50% of control patients and based on registry data in the Netherlands.

“There’s huge importance of this early detection in the screening arm,” Dr. de Koning said.

Additionally, an analysis of a subset of those with lung cancer showed a significant threefold increase in surgical treatment among the screened patients vs. those in the control arm who developed lung cancer (67.7% vs. 24.5%), he said.

CT screening reduced the risk of death from lung cancer by 9% to 41% in men over the course of the study, with an overall reduction of 26% at 10 years, and in a smaller subset of women, the rate-ratio of dying from lung cancer varied from 0.39 to 0.61 at different years of follow-up, he said, noting that this suggests a “significant and even larger reduction” in women.

Study participants were individuals aged 50-74 years in the Netherlands and Leuven, Belgium, who were considered at high risk for lung cancer based on responses to a general questionnaire. Participants’ records were linked with national registries with 100% coverage regarding cancer diagnosis and date and cause of death, and medical records for deceased lung cancer patients were reviewed by a blinded expert panel through 2013, and for the remaining study years cause of death as reported by Statistics Netherlands was used. Compliance among those randomized to the screening group was 86%, Dr. de Koning said.

“These findings show that CT screenings are an effective way to assess lung nodules in people at high risk for lung cancer, often leading to detection of suspicious nodules and subsequent surgical intervention at relatively low rates and with few false positives, and can positively increase the chances of cure in this devastating disease,” Dr. de Koning said in a press statement. “It is the second-largest trial in the world, with an even more favorable outcome than the first trial, the NLST, showed. These results should be used to inform and direct future CT screening in the world.”

During a press briefing, in response to a question about whether lung cancer screening should be offered more widely, he said that yes, countries – including the United States – should take note that “now two large-scale trials show large benefit.”

Dr. de Koning reported having no disclosures.

[email protected]

TORONTO – Neoadjuvant combined chemotherapy and immunotherapy (CT-IO) yielded high pathologic response rates for locally advanced, potentially resectable non-small cell lung cancer in the phase 2 multicenter study Nadim study.

Sharon Worcester/MDedge News

All 30 adults with stage IIIA N2 non-small cell lung cancer (NSCLC) who enrolled in the ongoing single-arm, open-label study and have undergone surgery to date, had resectable tumors following neoadjuvant treatment, Mariano Provencio, MD, of Hospital Puerta de Hierro, Madrid, Spain, reported at the World Conference on Lung Cancer.

The complete and partial response rates following the treatment were 10% and 60%, respectively, and the remaining patients had stable disease, Dr. Provencio said, noting that an additional 10 enrolled patients have completed treatment and are awaiting resection, and another 3 are still completing treatment.

The overall major pathologic response rate was 80%, including 75% with complete remission, he said at the conference, which was sponsored by the International Association for the Study of Lung Cancer.

“With a median follow-up of 4 months, no patients suffered any recurrence,” he said. “We have been unable to identify any significant factor related to the response, but we still do not have information about biomarkers.”

The study participants had a median age of 64 years, most (73%) were men, and all were current or former smokers. All received the planned neoadjuvant doses, which included 3 cycles of intravenous nivolumab at a dose of 360 mg every 3 weeks, plus 200 mg/m2 of paclitaxel and carboplatin at AUC 6 every 3 weeks.

“The most important toxicity was hematological toxicity related to chemotherapy; there were very few episodes of non-hematological toxicity,” he said.

Tumors were then assessed, and surgery–lobectomy in 90% of cases–was performed in the 3rd or 4th week after day 21 of the third neoadjuvant treatment cycle.

“There were no intraoperative complications, and 7 patients experienced some postoperative complications, but there was no postoperative mortality,” he said.

Adjuvant treatment included 240 mg of intravenous nivolumab every 2 weeks for 4 months and then 480 mg every 4 weeks for 8 months after resection.

The primary end-point of the study is 24-month progression-free survival.

CT-IO has a high response rate and longer survival in unselected patients with metastatic NSCLC, but there were previously no data about this combination in the neoadjuvant setting, Dr. Provencio said.

The findings of this ongoing study are limited by their preliminary nature and the related lack of information about overall survival and biomarkers, Dr. Provencio said.

Sharon Worcester/MDedge News

“But the higher complete remission and major pathological response rates make this a promising future treatment in stage 3 [NSCLC,] he said.

Indeed, the Nadim study thus far has shown “an amazing result that needs to be verified ... [there is] no prospective proof yet in this context that major pathologic response is parlayed with improved [progression-free survival] or [overall survival],” said discussant Corey Langer, MD, professor of medicine and director of thoracic oncology at the University of Pennsylvania, Philadelphia. “We need to track the late sequelae and [central nervous system] recurrences.”

Dr. Provencio reported relationships with AstraZeneca, Bristol-Meyers Squibb, Fabre, Merck, Pierre, Roche, and Bristol-Meyers Squibb. Dr. Langer reported relationships with numerous companies and organizations.

SOURCE: Provencio, Mario et al., WCLC 2018 Abstract OA01.05.

TORONTO – Neoadjuvant combined chemotherapy and immunotherapy (CT-IO) yielded high pathologic response rates for locally advanced, potentially resectable non-small cell lung cancer in the phase 2 multicenter study Nadim study.

Sharon Worcester/MDedge News

All 30 adults with stage IIIA N2 non-small cell lung cancer (NSCLC) who enrolled in the ongoing single-arm, open-label study and have undergone surgery to date, had resectable tumors following neoadjuvant treatment, Mariano Provencio, MD, of Hospital Puerta de Hierro, Madrid, Spain, reported at the World Conference on Lung Cancer.

The complete and partial response rates following the treatment were 10% and 60%, respectively, and the remaining patients had stable disease, Dr. Provencio said, noting that an additional 10 enrolled patients have completed treatment and are awaiting resection, and another 3 are still completing treatment.

The overall major pathologic response rate was 80%, including 75% with complete remission, he said at the conference, which was sponsored by the International Association for the Study of Lung Cancer.

“With a median follow-up of 4 months, no patients suffered any recurrence,” he said. “We have been unable to identify any significant factor related to the response, but we still do not have information about biomarkers.”

The study participants had a median age of 64 years, most (73%) were men, and all were current or former smokers. All received the planned neoadjuvant doses, which included 3 cycles of intravenous nivolumab at a dose of 360 mg every 3 weeks, plus 200 mg/m2 of paclitaxel and carboplatin at AUC 6 every 3 weeks.

“The most important toxicity was hematological toxicity related to chemotherapy; there were very few episodes of non-hematological toxicity,” he said.

Tumors were then assessed, and surgery–lobectomy in 90% of cases–was performed in the 3rd or 4th week after day 21 of the third neoadjuvant treatment cycle.

“There were no intraoperative complications, and 7 patients experienced some postoperative complications, but there was no postoperative mortality,” he said.

Adjuvant treatment included 240 mg of intravenous nivolumab every 2 weeks for 4 months and then 480 mg every 4 weeks for 8 months after resection.

The primary end-point of the study is 24-month progression-free survival.

CT-IO has a high response rate and longer survival in unselected patients with metastatic NSCLC, but there were previously no data about this combination in the neoadjuvant setting, Dr. Provencio said.

The findings of this ongoing study are limited by their preliminary nature and the related lack of information about overall survival and biomarkers, Dr. Provencio said.

Sharon Worcester/MDedge News

“But the higher complete remission and major pathological response rates make this a promising future treatment in stage 3 [NSCLC,] he said.

Indeed, the Nadim study thus far has shown “an amazing result that needs to be verified ... [there is] no prospective proof yet in this context that major pathologic response is parlayed with improved [progression-free survival] or [overall survival],” said discussant Corey Langer, MD, professor of medicine and director of thoracic oncology at the University of Pennsylvania, Philadelphia. “We need to track the late sequelae and [central nervous system] recurrences.”

Dr. Provencio reported relationships with AstraZeneca, Bristol-Meyers Squibb, Fabre, Merck, Pierre, Roche, and Bristol-Meyers Squibb. Dr. Langer reported relationships with numerous companies and organizations.

SOURCE: Provencio, Mario et al., WCLC 2018 Abstract OA01.05.

TORONTO – Neoadjuvant combined chemotherapy and immunotherapy (CT-IO) yielded high pathologic response rates for locally advanced, potentially resectable non-small cell lung cancer in the phase 2 multicenter study Nadim study.

Sharon Worcester/MDedge News

All 30 adults with stage IIIA N2 non-small cell lung cancer (NSCLC) who enrolled in the ongoing single-arm, open-label study and have undergone surgery to date, had resectable tumors following neoadjuvant treatment, Mariano Provencio, MD, of Hospital Puerta de Hierro, Madrid, Spain, reported at the World Conference on Lung Cancer.

The complete and partial response rates following the treatment were 10% and 60%, respectively, and the remaining patients had stable disease, Dr. Provencio said, noting that an additional 10 enrolled patients have completed treatment and are awaiting resection, and another 3 are still completing treatment.

The overall major pathologic response rate was 80%, including 75% with complete remission, he said at the conference, which was sponsored by the International Association for the Study of Lung Cancer.

“With a median follow-up of 4 months, no patients suffered any recurrence,” he said. “We have been unable to identify any significant factor related to the response, but we still do not have information about biomarkers.”

The study participants had a median age of 64 years, most (73%) were men, and all were current or former smokers. All received the planned neoadjuvant doses, which included 3 cycles of intravenous nivolumab at a dose of 360 mg every 3 weeks, plus 200 mg/m2 of paclitaxel and carboplatin at AUC 6 every 3 weeks.

“The most important toxicity was hematological toxicity related to chemotherapy; there were very few episodes of non-hematological toxicity,” he said.

Tumors were then assessed, and surgery–lobectomy in 90% of cases–was performed in the 3rd or 4th week after day 21 of the third neoadjuvant treatment cycle.

“There were no intraoperative complications, and 7 patients experienced some postoperative complications, but there was no postoperative mortality,” he said.

Adjuvant treatment included 240 mg of intravenous nivolumab every 2 weeks for 4 months and then 480 mg every 4 weeks for 8 months after resection.

The primary end-point of the study is 24-month progression-free survival.

CT-IO has a high response rate and longer survival in unselected patients with metastatic NSCLC, but there were previously no data about this combination in the neoadjuvant setting, Dr. Provencio said.

The findings of this ongoing study are limited by their preliminary nature and the related lack of information about overall survival and biomarkers, Dr. Provencio said.

Sharon Worcester/MDedge News

“But the higher complete remission and major pathological response rates make this a promising future treatment in stage 3 [NSCLC,] he said.

Indeed, the Nadim study thus far has shown “an amazing result that needs to be verified ... [there is] no prospective proof yet in this context that major pathologic response is parlayed with improved [progression-free survival] or [overall survival],” said discussant Corey Langer, MD, professor of medicine and director of thoracic oncology at the University of Pennsylvania, Philadelphia. “We need to track the late sequelae and [central nervous system] recurrences.”

Dr. Provencio reported relationships with AstraZeneca, Bristol-Meyers Squibb, Fabre, Merck, Pierre, Roche, and Bristol-Meyers Squibb. Dr. Langer reported relationships with numerous companies and organizations.

SOURCE: Provencio, Mario et al., WCLC 2018 Abstract OA01.05.

TORONTO – Comprehensive genetic profiling (CGP) helps identify targeted therapies for patients with cancer and facilitates clinical trial enrollment, according to findings from a retrospective study of 46 patients who were followed for 3 years after CGP.

A total of 263 genomic alterations were identified in the patients, leading to a change of therapy in 26% of cases and referral to a clinical trial in 13%, Kimberly Rohan, APN, reported at the World Conference on Lung Cancer.

The 13% referral rate was surprising, “because that’s way above the national average for enrollment in a clinical trial,” Ms. Rohan, of the Edward Cancer Center in Naperville, Ill., said during a press briefing at the meeting, sponsored by the International Association for the Study of Lung Cancer.

“Among those diagnosed with lung cancer, 6% were referred to clinical trials and 34% had a change of therapy,” she said, noting that all but one of the patients had non–small cell lung cancer, and the other had small cell lung cancer and many alterations.

Of note, three patients enrolled in hospice care based on the findings; sometimes, palliative care is the most appropriate option, and this information helps patients and their families make those decisions, Ms. Rohan said.

Patients were tested between 2014 and 2017, and the review looked at the number of genomic alterations identified in each, what treatments were associated with potential clinical trial benefits, what therapies were associated with lack of response, and the effects of the CGP findings on decision making.

An important next step is to work with payors to get them to pay for CGP testing, she said. “These tests are expensive so a lot of [insurance companies] don’t want to pay for them, but this data will help support the fact that [these tests] do allow better treatments for patients and allow patients to make better decisions for themselves in regard to treatment.”

Ms. Rohan is a speaker or advisory board member for Merck, Genentech, and AstraZeneca.

TORONTO – Comprehensive genetic profiling (CGP) helps identify targeted therapies for patients with cancer and facilitates clinical trial enrollment, according to findings from a retrospective study of 46 patients who were followed for 3 years after CGP.

A total of 263 genomic alterations were identified in the patients, leading to a change of therapy in 26% of cases and referral to a clinical trial in 13%, Kimberly Rohan, APN, reported at the World Conference on Lung Cancer.

The 13% referral rate was surprising, “because that’s way above the national average for enrollment in a clinical trial,” Ms. Rohan, of the Edward Cancer Center in Naperville, Ill., said during a press briefing at the meeting, sponsored by the International Association for the Study of Lung Cancer.

“Among those diagnosed with lung cancer, 6% were referred to clinical trials and 34% had a change of therapy,” she said, noting that all but one of the patients had non–small cell lung cancer, and the other had small cell lung cancer and many alterations.

Of note, three patients enrolled in hospice care based on the findings; sometimes, palliative care is the most appropriate option, and this information helps patients and their families make those decisions, Ms. Rohan said.

Patients were tested between 2014 and 2017, and the review looked at the number of genomic alterations identified in each, what treatments were associated with potential clinical trial benefits, what therapies were associated with lack of response, and the effects of the CGP findings on decision making.

An important next step is to work with payors to get them to pay for CGP testing, she said. “These tests are expensive so a lot of [insurance companies] don’t want to pay for them, but this data will help support the fact that [these tests] do allow better treatments for patients and allow patients to make better decisions for themselves in regard to treatment.”

Ms. Rohan is a speaker or advisory board member for Merck, Genentech, and AstraZeneca.

TORONTO – Comprehensive genetic profiling (CGP) helps identify targeted therapies for patients with cancer and facilitates clinical trial enrollment, according to findings from a retrospective study of 46 patients who were followed for 3 years after CGP.

A total of 263 genomic alterations were identified in the patients, leading to a change of therapy in 26% of cases and referral to a clinical trial in 13%, Kimberly Rohan, APN, reported at the World Conference on Lung Cancer.

The 13% referral rate was surprising, “because that’s way above the national average for enrollment in a clinical trial,” Ms. Rohan, of the Edward Cancer Center in Naperville, Ill., said during a press briefing at the meeting, sponsored by the International Association for the Study of Lung Cancer.

“Among those diagnosed with lung cancer, 6% were referred to clinical trials and 34% had a change of therapy,” she said, noting that all but one of the patients had non–small cell lung cancer, and the other had small cell lung cancer and many alterations.

Of note, three patients enrolled in hospice care based on the findings; sometimes, palliative care is the most appropriate option, and this information helps patients and their families make those decisions, Ms. Rohan said.

Patients were tested between 2014 and 2017, and the review looked at the number of genomic alterations identified in each, what treatments were associated with potential clinical trial benefits, what therapies were associated with lack of response, and the effects of the CGP findings on decision making.

An important next step is to work with payors to get them to pay for CGP testing, she said. “These tests are expensive so a lot of [insurance companies] don’t want to pay for them, but this data will help support the fact that [these tests] do allow better treatments for patients and allow patients to make better decisions for themselves in regard to treatment.”

Ms. Rohan is a speaker or advisory board member for Merck, Genentech, and AstraZeneca.