Sharon Worcester

EDINBURGH – Treatment induction with obinutuzumab and ibrutinib followed by a minimal residual disease (MRD)–driven treatment strategy in patients with chronic lymphocytic leukemia (CLL) yields a high long-term complete response rate and prolonged progression-free and overall survival, according to findings from the phase 2 ICLL-07 trial.

The intent-to-treat (ITT) complete response rate at 16 months in 135 patients who were treated with this strategy was 62%, Anne-Sophie Michallet, MD, reported at the International Workshop on Chronic Lymphocytic Leukemia.

Patients in the multicenter, open-label trial conducted by the French Innovative Leukemia Organization (FILO) were previously untreated, medically fit patients with CLL and no 17p deletion. They were enrolled between November 2015 and May 2017 to receive eight 1,000 mg IV doses of obinutuzumab over six 4-week cycles along with oral Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib at a dose of 420 mg daily for 9 months.

Ten patients (7.7%) achieved complete response with bone marrow MRD less than 0.01% (undetectable) at 9 months and, by study protocol, continued on only the ibrutinib for 6 additional months. The remaining 120 evaluable patients received four 4-week cycles of fludarabine/cyclophosphamide along with the obinutuzumab and ibrutinib for 6 additional months, explained Dr. Michallet of Centre Léon Bérard, Lyon, France.

The ITT rate at 16 months – the primary endpoint of the study – was achieved with no more than four cycles of fludarabine/cyclophosphamide and obinutuzumab, and exceeded the primary objective of demonstrating a 30% or higher rate of complete response with bone marrow MRD less than 0.01% at the month 16 ITT analysis, she said.

“The ... strategy yielded an overall response rate of 100%, a complete response rate, according to iwCLL [criteria], of 73%, a bone marrow MRD–undetectable rate of 79% [in the ITT population],” she said, adding that the primary objective was achieved with a complete response with a peripheral blood and bone marrow MRD–undetectable rate of 62%.

Response assessments at months 9 and 16 involved whole-body computed tomography scans with tumor measurements and bone marrow trephine biopsy for patients in clinical complete response. MRD testing was performed by eight-color flow cytometry in both peripheral blood and bone marrow.

After month 16, response was clinically assessed every 3 months, and peripheral blood MRD was assessed every 6 months until month 40.

“With a median follow-up of 26.3 months, the 2-year progression-free survival and overall survival were, respectively, 97% and 97.5%,” Dr. Michallet said, noting that the longitudinal follow-up of peripheral blood MRD in the entire cohort showed durability of a deep response. The rate of peripheral blood MRD less than 0.01% at 22 months was 77% in the 10 patients who received only ibrutinib after the 9-month assessment, and 93% in those who received fludarabine/cyclophosphamide after the 9-month assessment.

In patients with immunoglobulin heavy gene variable (IGHV) mutations, the rate of peripheral blood MRD less than 0.01% at month 22 was 96%, and in those without IGHV mutations, the rate was 77%, she noted.

The findings demonstrate that the approach has merit in medically fit, treatment-naive patients with CLL and no 17p deletion, she said, explaining that the fixed-duration, MRD-driven strategy used in this study was developed to “avoid or at least reduce chemotherapy exposure” in the first-line treatment of such patients.

Indeed, the approach was associated with “a high [complete response] rate, a high level of undetectable bone marrow MRD, an acceptable safety profile, and a sustained MRD negativity rate at 12 months after the end of the treatment,” she said.

“This highly effective strategy combining a BTK inhibitor and abbreviated immunochemotherapy deserves further investigation with randomized trials,” she concluded.

ICLL-07 FILO was funded by Roche and Janssen. Dr. Michallet reported having no disclosures.

[email protected]

EDINBURGH – Treatment induction with obinutuzumab and ibrutinib followed by a minimal residual disease (MRD)–driven treatment strategy in patients with chronic lymphocytic leukemia (CLL) yields a high long-term complete response rate and prolonged progression-free and overall survival, according to findings from the phase 2 ICLL-07 trial.

The intent-to-treat (ITT) complete response rate at 16 months in 135 patients who were treated with this strategy was 62%, Anne-Sophie Michallet, MD, reported at the International Workshop on Chronic Lymphocytic Leukemia.

Patients in the multicenter, open-label trial conducted by the French Innovative Leukemia Organization (FILO) were previously untreated, medically fit patients with CLL and no 17p deletion. They were enrolled between November 2015 and May 2017 to receive eight 1,000 mg IV doses of obinutuzumab over six 4-week cycles along with oral Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib at a dose of 420 mg daily for 9 months.

Ten patients (7.7%) achieved complete response with bone marrow MRD less than 0.01% (undetectable) at 9 months and, by study protocol, continued on only the ibrutinib for 6 additional months. The remaining 120 evaluable patients received four 4-week cycles of fludarabine/cyclophosphamide along with the obinutuzumab and ibrutinib for 6 additional months, explained Dr. Michallet of Centre Léon Bérard, Lyon, France.

The ITT rate at 16 months – the primary endpoint of the study – was achieved with no more than four cycles of fludarabine/cyclophosphamide and obinutuzumab, and exceeded the primary objective of demonstrating a 30% or higher rate of complete response with bone marrow MRD less than 0.01% at the month 16 ITT analysis, she said.

“The ... strategy yielded an overall response rate of 100%, a complete response rate, according to iwCLL [criteria], of 73%, a bone marrow MRD–undetectable rate of 79% [in the ITT population],” she said, adding that the primary objective was achieved with a complete response with a peripheral blood and bone marrow MRD–undetectable rate of 62%.

Response assessments at months 9 and 16 involved whole-body computed tomography scans with tumor measurements and bone marrow trephine biopsy for patients in clinical complete response. MRD testing was performed by eight-color flow cytometry in both peripheral blood and bone marrow.

After month 16, response was clinically assessed every 3 months, and peripheral blood MRD was assessed every 6 months until month 40.

“With a median follow-up of 26.3 months, the 2-year progression-free survival and overall survival were, respectively, 97% and 97.5%,” Dr. Michallet said, noting that the longitudinal follow-up of peripheral blood MRD in the entire cohort showed durability of a deep response. The rate of peripheral blood MRD less than 0.01% at 22 months was 77% in the 10 patients who received only ibrutinib after the 9-month assessment, and 93% in those who received fludarabine/cyclophosphamide after the 9-month assessment.

In patients with immunoglobulin heavy gene variable (IGHV) mutations, the rate of peripheral blood MRD less than 0.01% at month 22 was 96%, and in those without IGHV mutations, the rate was 77%, she noted.

The findings demonstrate that the approach has merit in medically fit, treatment-naive patients with CLL and no 17p deletion, she said, explaining that the fixed-duration, MRD-driven strategy used in this study was developed to “avoid or at least reduce chemotherapy exposure” in the first-line treatment of such patients.

Indeed, the approach was associated with “a high [complete response] rate, a high level of undetectable bone marrow MRD, an acceptable safety profile, and a sustained MRD negativity rate at 12 months after the end of the treatment,” she said.

“This highly effective strategy combining a BTK inhibitor and abbreviated immunochemotherapy deserves further investigation with randomized trials,” she concluded.

ICLL-07 FILO was funded by Roche and Janssen. Dr. Michallet reported having no disclosures.

[email protected]

EDINBURGH – Treatment induction with obinutuzumab and ibrutinib followed by a minimal residual disease (MRD)–driven treatment strategy in patients with chronic lymphocytic leukemia (CLL) yields a high long-term complete response rate and prolonged progression-free and overall survival, according to findings from the phase 2 ICLL-07 trial.

The intent-to-treat (ITT) complete response rate at 16 months in 135 patients who were treated with this strategy was 62%, Anne-Sophie Michallet, MD, reported at the International Workshop on Chronic Lymphocytic Leukemia.

Patients in the multicenter, open-label trial conducted by the French Innovative Leukemia Organization (FILO) were previously untreated, medically fit patients with CLL and no 17p deletion. They were enrolled between November 2015 and May 2017 to receive eight 1,000 mg IV doses of obinutuzumab over six 4-week cycles along with oral Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib at a dose of 420 mg daily for 9 months.

Ten patients (7.7%) achieved complete response with bone marrow MRD less than 0.01% (undetectable) at 9 months and, by study protocol, continued on only the ibrutinib for 6 additional months. The remaining 120 evaluable patients received four 4-week cycles of fludarabine/cyclophosphamide along with the obinutuzumab and ibrutinib for 6 additional months, explained Dr. Michallet of Centre Léon Bérard, Lyon, France.

The ITT rate at 16 months – the primary endpoint of the study – was achieved with no more than four cycles of fludarabine/cyclophosphamide and obinutuzumab, and exceeded the primary objective of demonstrating a 30% or higher rate of complete response with bone marrow MRD less than 0.01% at the month 16 ITT analysis, she said.

“The ... strategy yielded an overall response rate of 100%, a complete response rate, according to iwCLL [criteria], of 73%, a bone marrow MRD–undetectable rate of 79% [in the ITT population],” she said, adding that the primary objective was achieved with a complete response with a peripheral blood and bone marrow MRD–undetectable rate of 62%.

Response assessments at months 9 and 16 involved whole-body computed tomography scans with tumor measurements and bone marrow trephine biopsy for patients in clinical complete response. MRD testing was performed by eight-color flow cytometry in both peripheral blood and bone marrow.

After month 16, response was clinically assessed every 3 months, and peripheral blood MRD was assessed every 6 months until month 40.

“With a median follow-up of 26.3 months, the 2-year progression-free survival and overall survival were, respectively, 97% and 97.5%,” Dr. Michallet said, noting that the longitudinal follow-up of peripheral blood MRD in the entire cohort showed durability of a deep response. The rate of peripheral blood MRD less than 0.01% at 22 months was 77% in the 10 patients who received only ibrutinib after the 9-month assessment, and 93% in those who received fludarabine/cyclophosphamide after the 9-month assessment.

In patients with immunoglobulin heavy gene variable (IGHV) mutations, the rate of peripheral blood MRD less than 0.01% at month 22 was 96%, and in those without IGHV mutations, the rate was 77%, she noted.

The findings demonstrate that the approach has merit in medically fit, treatment-naive patients with CLL and no 17p deletion, she said, explaining that the fixed-duration, MRD-driven strategy used in this study was developed to “avoid or at least reduce chemotherapy exposure” in the first-line treatment of such patients.

Indeed, the approach was associated with “a high [complete response] rate, a high level of undetectable bone marrow MRD, an acceptable safety profile, and a sustained MRD negativity rate at 12 months after the end of the treatment,” she said.

“This highly effective strategy combining a BTK inhibitor and abbreviated immunochemotherapy deserves further investigation with randomized trials,” she concluded.

ICLL-07 FILO was funded by Roche and Janssen. Dr. Michallet reported having no disclosures.

[email protected]

BARCELONA – Cancer drug prices are significantly higher in the United States than in Europe, and they don’t correlate with clinical benefit in either region, according to an analysis of drug costs and value-related scores between 2009 and 2018.

Of 63 cancer drugs approved by the Food and Drug Administration between 2009 and 2017 and by the European Medicines Agency as of December 31, 2018, 46 (73%) were approved for solid tumors, and 17 (27%) for hematologic malignancies. Median cancer drug prices in Europe were 52% lower than U.S. prices, Kerstin N. Vokinger, MD, Academic Chair For Health Policy at the Institute For Primary Care, University Hospital Zürich, and colleagues found.

The findings were released via press release at the European Society for Medical Oncology (ESMO) Congress and will be part of a poster discussion session there.

The investigators found no association between monthly treatment cost and the American Society of Clinical Oncology Value Framework (ASCO-VF) or the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) scores in any country. They also found no association between the price differential in the United States and Europe and either ASCO-VF (P = .599) or ESMO-MBCS (P = .321) scores.

For the analysis, they assessed U.S. average sales prices or, when those weren’t available, wholesale acquisition costs as of Feb. 1, 2019, and compared them with comparable currency-adjusted ex-factory drug costs in England, France, Germany, and Switzerland.

ASCO-VF and ESMO-MCBS scores were then assessed based on the highest score from pivotal trials supporting each solid tumor drug.

The median monthly cost for drugs with low-benefit scores on ESMO-MCBS ranged from $4,361-$5,273 in the European countries, compared with $12,436 in the United States, according to the release.

“Drug costs were not associated with clinical benefit score in any of the countries we looked at. For example, some of the more expensive drugs for prostate and lung cancer in Switzerland had lower ESMO-MCBS scores, while cheaper drugs had higher scores,” said Dr. Vokinger, who also is affiliated with the Program on Regulation, Therapeutics, and Law at Harvard Medical School, Boston. “It is important that drug pricing is aligned with clinical value and that our limited resources are spent on innovative medicines that offer improved outcomes.”

Barbara Kiesewetter, MD, of the Medical University of Vienna and a member of the ESMO-MCBS Working Group, said the findings underscore the importance of using the scoring systems in clinical practice to assist in treatment-related decision making.

The ESMO-MCBS, for example, is available online, easy to use, and helps explain “the factors that are used to grade the clinical benefit of medicines.

“It’s very important to have this validated score not only for daily decision making, but to influence reimbursement decisions and reduce treatment disparities,” she said, also noting in the release that “[c]ost is one of the main reasons why patients are denied access to the newer anticancer drugs.”

“By showing which drugs are most likely to be worth the higher cost, we can hopefully improve access to the drugs with greatest value so that patients receive standardized, optimal therapy wherever they live,” she said.

The study was funded by the Swiss Cancer League. The authors reported having no conflicts of interest.

SOURCE: Vokinger KN et al. ESMO 2019, Abstract 1631PD-PR.

BARCELONA – Cancer drug prices are significantly higher in the United States than in Europe, and they don’t correlate with clinical benefit in either region, according to an analysis of drug costs and value-related scores between 2009 and 2018.

Of 63 cancer drugs approved by the Food and Drug Administration between 2009 and 2017 and by the European Medicines Agency as of December 31, 2018, 46 (73%) were approved for solid tumors, and 17 (27%) for hematologic malignancies. Median cancer drug prices in Europe were 52% lower than U.S. prices, Kerstin N. Vokinger, MD, Academic Chair For Health Policy at the Institute For Primary Care, University Hospital Zürich, and colleagues found.

The findings were released via press release at the European Society for Medical Oncology (ESMO) Congress and will be part of a poster discussion session there.

The investigators found no association between monthly treatment cost and the American Society of Clinical Oncology Value Framework (ASCO-VF) or the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) scores in any country. They also found no association between the price differential in the United States and Europe and either ASCO-VF (P = .599) or ESMO-MBCS (P = .321) scores.

For the analysis, they assessed U.S. average sales prices or, when those weren’t available, wholesale acquisition costs as of Feb. 1, 2019, and compared them with comparable currency-adjusted ex-factory drug costs in England, France, Germany, and Switzerland.

ASCO-VF and ESMO-MCBS scores were then assessed based on the highest score from pivotal trials supporting each solid tumor drug.

The median monthly cost for drugs with low-benefit scores on ESMO-MCBS ranged from $4,361-$5,273 in the European countries, compared with $12,436 in the United States, according to the release.

“Drug costs were not associated with clinical benefit score in any of the countries we looked at. For example, some of the more expensive drugs for prostate and lung cancer in Switzerland had lower ESMO-MCBS scores, while cheaper drugs had higher scores,” said Dr. Vokinger, who also is affiliated with the Program on Regulation, Therapeutics, and Law at Harvard Medical School, Boston. “It is important that drug pricing is aligned with clinical value and that our limited resources are spent on innovative medicines that offer improved outcomes.”

Barbara Kiesewetter, MD, of the Medical University of Vienna and a member of the ESMO-MCBS Working Group, said the findings underscore the importance of using the scoring systems in clinical practice to assist in treatment-related decision making.

The ESMO-MCBS, for example, is available online, easy to use, and helps explain “the factors that are used to grade the clinical benefit of medicines.

“It’s very important to have this validated score not only for daily decision making, but to influence reimbursement decisions and reduce treatment disparities,” she said, also noting in the release that “[c]ost is one of the main reasons why patients are denied access to the newer anticancer drugs.”

“By showing which drugs are most likely to be worth the higher cost, we can hopefully improve access to the drugs with greatest value so that patients receive standardized, optimal therapy wherever they live,” she said.

The study was funded by the Swiss Cancer League. The authors reported having no conflicts of interest.

SOURCE: Vokinger KN et al. ESMO 2019, Abstract 1631PD-PR.

BARCELONA – Cancer drug prices are significantly higher in the United States than in Europe, and they don’t correlate with clinical benefit in either region, according to an analysis of drug costs and value-related scores between 2009 and 2018.

Of 63 cancer drugs approved by the Food and Drug Administration between 2009 and 2017 and by the European Medicines Agency as of December 31, 2018, 46 (73%) were approved for solid tumors, and 17 (27%) for hematologic malignancies. Median cancer drug prices in Europe were 52% lower than U.S. prices, Kerstin N. Vokinger, MD, Academic Chair For Health Policy at the Institute For Primary Care, University Hospital Zürich, and colleagues found.

The findings were released via press release at the European Society for Medical Oncology (ESMO) Congress and will be part of a poster discussion session there.

The investigators found no association between monthly treatment cost and the American Society of Clinical Oncology Value Framework (ASCO-VF) or the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) scores in any country. They also found no association between the price differential in the United States and Europe and either ASCO-VF (P = .599) or ESMO-MBCS (P = .321) scores.

For the analysis, they assessed U.S. average sales prices or, when those weren’t available, wholesale acquisition costs as of Feb. 1, 2019, and compared them with comparable currency-adjusted ex-factory drug costs in England, France, Germany, and Switzerland.

ASCO-VF and ESMO-MCBS scores were then assessed based on the highest score from pivotal trials supporting each solid tumor drug.

The median monthly cost for drugs with low-benefit scores on ESMO-MCBS ranged from $4,361-$5,273 in the European countries, compared with $12,436 in the United States, according to the release.

“Drug costs were not associated with clinical benefit score in any of the countries we looked at. For example, some of the more expensive drugs for prostate and lung cancer in Switzerland had lower ESMO-MCBS scores, while cheaper drugs had higher scores,” said Dr. Vokinger, who also is affiliated with the Program on Regulation, Therapeutics, and Law at Harvard Medical School, Boston. “It is important that drug pricing is aligned with clinical value and that our limited resources are spent on innovative medicines that offer improved outcomes.”

Barbara Kiesewetter, MD, of the Medical University of Vienna and a member of the ESMO-MCBS Working Group, said the findings underscore the importance of using the scoring systems in clinical practice to assist in treatment-related decision making.

The ESMO-MCBS, for example, is available online, easy to use, and helps explain “the factors that are used to grade the clinical benefit of medicines.

“It’s very important to have this validated score not only for daily decision making, but to influence reimbursement decisions and reduce treatment disparities,” she said, also noting in the release that “[c]ost is one of the main reasons why patients are denied access to the newer anticancer drugs.”

“By showing which drugs are most likely to be worth the higher cost, we can hopefully improve access to the drugs with greatest value so that patients receive standardized, optimal therapy wherever they live,” she said.

The study was funded by the Swiss Cancer League. The authors reported having no conflicts of interest.

SOURCE: Vokinger KN et al. ESMO 2019, Abstract 1631PD-PR.

EDINBURGH – Consolidation therapy with obinutuzumab after chemoimmunotherapy for B-cell chronic lymphocytic leukemia (B-CLL) was highly effective for eradicating minimal residual disease (MRD) within 6 months following randomization in the seamless phase 2/3 GALACTIC trial.

Of 14 patients who were MRD positive after chemoimmunotherapy and randomized to consolidation with the type II monoclonal antibody targeting the CD20 antigen, 10 achieved MRD negativity in the bone marrow by 6 months, and 13 achieved MRD negativity in the peripheral blood by 6 months, Talha Munir, MD, reported at the International Workshop on Chronic Lymphocytic Leukemia.

“And that translated into [progression-free survival] improvement in the consolidation arm,” said Dr. Munir of St. James’s University, Leeds, England.

The median progression-free survival in that arm was not reached, whereas progression-free survival in 15 MRD-positive patients randomized to the nonconsolidation arm was 16.6 months, he said.

Further, no difference was seen in median progression-free survival, overall survival, or MRD duration between the consolidation arm and 19 patients who were not randomized because of MRD negativity after chemoimmunotherapy, he noted.

Achieving MRD negativity in CLL confers a survival advantage, and obinutuzumab has shown greater efficacy with respect to MRD in CLL when compared with previous anti-CD20 antibodies, and it is less immune suppressive than the anti-CD52 antibody alemtuzumab, he explained.

The GALACTIC trial was designed to assess the safety and efficacy of obinutuzumab consolidation for eradicating MRD and whether its effects would prolong progression-free survival in patients with B-CLL who recently responded to chemoimmunotherapy. Those achieving complete response or partial response at 3-24 months after chemoimmunotherapy, and who remained MRD-positive, were eligible for randomization.

The planned sample size was 188 patients, but the trial was closed early in February 2017 because of poor recruitment; a total of 48 patients were enrolled, including the 19 nonrandomized, MRD-negative patients.

Patients randomized to consolidation received 1,000 mg of obinutuzumab weekly for the first four doses, and then every other week for four additional doses.

Obinutuzumab was well tolerated with minimal infusion-related reactions and toxicity, Dr. Munir said.

Despite the low recruitment, both the phase 2 and 3 endpoints were assessed as positive, because the consolidation strategy was so efficacious, Dr. Munir noted, concluding that the findings provide further evidence of the value of MRD negativity for improving outcomes in CLL.

The GALACTIC trial was developed by the GALACTIC Trial Management Group with the support of the UKCLL/NCRI CLL Clinical Trials Subgroup. The trial is funded by Cancer Research UK and Roche and sponsored by the University of Leeds. Dr. Munir reported having no disclosures.

[email protected]

EDINBURGH – Consolidation therapy with obinutuzumab after chemoimmunotherapy for B-cell chronic lymphocytic leukemia (B-CLL) was highly effective for eradicating minimal residual disease (MRD) within 6 months following randomization in the seamless phase 2/3 GALACTIC trial.

Of 14 patients who were MRD positive after chemoimmunotherapy and randomized to consolidation with the type II monoclonal antibody targeting the CD20 antigen, 10 achieved MRD negativity in the bone marrow by 6 months, and 13 achieved MRD negativity in the peripheral blood by 6 months, Talha Munir, MD, reported at the International Workshop on Chronic Lymphocytic Leukemia.

“And that translated into [progression-free survival] improvement in the consolidation arm,” said Dr. Munir of St. James’s University, Leeds, England.

The median progression-free survival in that arm was not reached, whereas progression-free survival in 15 MRD-positive patients randomized to the nonconsolidation arm was 16.6 months, he said.

Further, no difference was seen in median progression-free survival, overall survival, or MRD duration between the consolidation arm and 19 patients who were not randomized because of MRD negativity after chemoimmunotherapy, he noted.

Achieving MRD negativity in CLL confers a survival advantage, and obinutuzumab has shown greater efficacy with respect to MRD in CLL when compared with previous anti-CD20 antibodies, and it is less immune suppressive than the anti-CD52 antibody alemtuzumab, he explained.

The GALACTIC trial was designed to assess the safety and efficacy of obinutuzumab consolidation for eradicating MRD and whether its effects would prolong progression-free survival in patients with B-CLL who recently responded to chemoimmunotherapy. Those achieving complete response or partial response at 3-24 months after chemoimmunotherapy, and who remained MRD-positive, were eligible for randomization.

The planned sample size was 188 patients, but the trial was closed early in February 2017 because of poor recruitment; a total of 48 patients were enrolled, including the 19 nonrandomized, MRD-negative patients.

Patients randomized to consolidation received 1,000 mg of obinutuzumab weekly for the first four doses, and then every other week for four additional doses.

Obinutuzumab was well tolerated with minimal infusion-related reactions and toxicity, Dr. Munir said.

Despite the low recruitment, both the phase 2 and 3 endpoints were assessed as positive, because the consolidation strategy was so efficacious, Dr. Munir noted, concluding that the findings provide further evidence of the value of MRD negativity for improving outcomes in CLL.

The GALACTIC trial was developed by the GALACTIC Trial Management Group with the support of the UKCLL/NCRI CLL Clinical Trials Subgroup. The trial is funded by Cancer Research UK and Roche and sponsored by the University of Leeds. Dr. Munir reported having no disclosures.

[email protected]

EDINBURGH – Consolidation therapy with obinutuzumab after chemoimmunotherapy for B-cell chronic lymphocytic leukemia (B-CLL) was highly effective for eradicating minimal residual disease (MRD) within 6 months following randomization in the seamless phase 2/3 GALACTIC trial.

Of 14 patients who were MRD positive after chemoimmunotherapy and randomized to consolidation with the type II monoclonal antibody targeting the CD20 antigen, 10 achieved MRD negativity in the bone marrow by 6 months, and 13 achieved MRD negativity in the peripheral blood by 6 months, Talha Munir, MD, reported at the International Workshop on Chronic Lymphocytic Leukemia.

“And that translated into [progression-free survival] improvement in the consolidation arm,” said Dr. Munir of St. James’s University, Leeds, England.

The median progression-free survival in that arm was not reached, whereas progression-free survival in 15 MRD-positive patients randomized to the nonconsolidation arm was 16.6 months, he said.

Further, no difference was seen in median progression-free survival, overall survival, or MRD duration between the consolidation arm and 19 patients who were not randomized because of MRD negativity after chemoimmunotherapy, he noted.

Achieving MRD negativity in CLL confers a survival advantage, and obinutuzumab has shown greater efficacy with respect to MRD in CLL when compared with previous anti-CD20 antibodies, and it is less immune suppressive than the anti-CD52 antibody alemtuzumab, he explained.

The GALACTIC trial was designed to assess the safety and efficacy of obinutuzumab consolidation for eradicating MRD and whether its effects would prolong progression-free survival in patients with B-CLL who recently responded to chemoimmunotherapy. Those achieving complete response or partial response at 3-24 months after chemoimmunotherapy, and who remained MRD-positive, were eligible for randomization.

The planned sample size was 188 patients, but the trial was closed early in February 2017 because of poor recruitment; a total of 48 patients were enrolled, including the 19 nonrandomized, MRD-negative patients.

Patients randomized to consolidation received 1,000 mg of obinutuzumab weekly for the first four doses, and then every other week for four additional doses.

Obinutuzumab was well tolerated with minimal infusion-related reactions and toxicity, Dr. Munir said.

Despite the low recruitment, both the phase 2 and 3 endpoints were assessed as positive, because the consolidation strategy was so efficacious, Dr. Munir noted, concluding that the findings provide further evidence of the value of MRD negativity for improving outcomes in CLL.

The GALACTIC trial was developed by the GALACTIC Trial Management Group with the support of the UKCLL/NCRI CLL Clinical Trials Subgroup. The trial is funded by Cancer Research UK and Roche and sponsored by the University of Leeds. Dr. Munir reported having no disclosures.

[email protected]

BARCELONA – First-line pembrolizumab provides a durable long-term overall survival (OS) benefit, compared with that of chemotherapy, in patients with advanced nonsquamous non–small cell lung cancer (NSCLC), according to 3-year data from the phase 3 Keynote-024 trial.

As previously reported, first-line treatment with the programmed death-1 (PD-1) inhibitor significantly improved progression-free survival (PFS) and OS, compared with those of platinum-based chemotherapy, and had fewer adverse events after a median of 11.2 months of follow-up in the open-label trial. In 305 patients with advanced NSCLC, high PD-L1 expression, and an absence of targetable epidermal growth factor or anaplastic lymphoma kinase gene alterations, median PFS was 10.3 months vs. 6.0 months, and estimated OS was 80.2% vs. 72.4% in the groups, respectively (hazard ratios, 0.50 and 0.60, respectively).

At 3 years after treatment initiation, median OS was 26.3 months vs. 14.2 months in patients treated with pembrolizumab or chemotherapy (HR, 0.65), respectively, and the OS rates were 43.7% and 24.9%, Martin Reck, MD, reported at the World Conference on Lung Cancer.

This was despite 98 of 151 patients assigned to chemotherapy crossing over to pembrolizumab, Dr. Reck, head of the department of thoracic oncology and the clinical trial department in the department of thoracic oncology at the Lung Clinic Grosshansdorf (Germany), noted at the conference, which was sponsored by the International Association for the Study of Lung Cancer.

Additionally, despite longer mean treatment duration in the pembrolizumab arm than in the chemotherapy arm (11.1 vs. 4.4 months), grade 3-5 treatment-related adverse events were less frequent with pembrolizumab than with chemotherapy (31.2% vs. 53.3%), he said.

Of 38 patients in the pembrolizumab arm who completed 2 years of therapy, 34 were alive at 3 years, and 31 (81.6%) had an objective response, including 2 who had a complete response. Median duration of response was not reached, and OS was 97.4%.

Grade 3-5 adverse events occurred in 5 (13.2%) of those patients; no fatal treatment-related adverse events occurred.

Of note, 7 of 10 patients who completed 2 years of treatment, but who subsequently progressed, experienced an objective response with a second course of pembrolizumab, and 8 remain alive, he said.

Patients in KEYNOTE-024 were randomized to receive 200 mg of pembrolizumab every 3 weeks for 2 years or investigator’s choice of platinum doublet for 4-6 cycles plus optional maintenance, with stratification by performance status, tumor histology, and region.

The findings confirm the long-term efficacy of pembrolizumab, compared with platinum-based chemotherapy, demonstrate “consistent benefit in overall survival ... despite a crossover of 65%,” and show the first signs of efficacy with reexposure to pembrolizumab at the time of progression.

“This is work in progress; currently we have data from 10 [reexposed] patients, but what we do see is clinical activity even after [reexposure] to pembrolizumab, so we do see a stabilization of response to the disease in 70% of the patients, and 50% are ongoing.”

The findings highlight a new reality: “There are really some patients who have this disease as a chronic disease induced by immunotherapy.” Dr. Reck said.

KEYNOTE-024 was funded by Merck Sharp & Dohme. Dr. Reck reported receiving personal fees/honoraria for consultancy and lectures from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Merck Sharp & Dohme, MSD, Eli Lilly, Pfizer, AbbVie, Roche, and Novartis.

SOURCE: Reck M et al. WCLC 2019, Abstract OA14.01.

BARCELONA – First-line pembrolizumab provides a durable long-term overall survival (OS) benefit, compared with that of chemotherapy, in patients with advanced nonsquamous non–small cell lung cancer (NSCLC), according to 3-year data from the phase 3 Keynote-024 trial.

As previously reported, first-line treatment with the programmed death-1 (PD-1) inhibitor significantly improved progression-free survival (PFS) and OS, compared with those of platinum-based chemotherapy, and had fewer adverse events after a median of 11.2 months of follow-up in the open-label trial. In 305 patients with advanced NSCLC, high PD-L1 expression, and an absence of targetable epidermal growth factor or anaplastic lymphoma kinase gene alterations, median PFS was 10.3 months vs. 6.0 months, and estimated OS was 80.2% vs. 72.4% in the groups, respectively (hazard ratios, 0.50 and 0.60, respectively).

At 3 years after treatment initiation, median OS was 26.3 months vs. 14.2 months in patients treated with pembrolizumab or chemotherapy (HR, 0.65), respectively, and the OS rates were 43.7% and 24.9%, Martin Reck, MD, reported at the World Conference on Lung Cancer.

This was despite 98 of 151 patients assigned to chemotherapy crossing over to pembrolizumab, Dr. Reck, head of the department of thoracic oncology and the clinical trial department in the department of thoracic oncology at the Lung Clinic Grosshansdorf (Germany), noted at the conference, which was sponsored by the International Association for the Study of Lung Cancer.

Additionally, despite longer mean treatment duration in the pembrolizumab arm than in the chemotherapy arm (11.1 vs. 4.4 months), grade 3-5 treatment-related adverse events were less frequent with pembrolizumab than with chemotherapy (31.2% vs. 53.3%), he said.

Of 38 patients in the pembrolizumab arm who completed 2 years of therapy, 34 were alive at 3 years, and 31 (81.6%) had an objective response, including 2 who had a complete response. Median duration of response was not reached, and OS was 97.4%.

Grade 3-5 adverse events occurred in 5 (13.2%) of those patients; no fatal treatment-related adverse events occurred.

Of note, 7 of 10 patients who completed 2 years of treatment, but who subsequently progressed, experienced an objective response with a second course of pembrolizumab, and 8 remain alive, he said.

Patients in KEYNOTE-024 were randomized to receive 200 mg of pembrolizumab every 3 weeks for 2 years or investigator’s choice of platinum doublet for 4-6 cycles plus optional maintenance, with stratification by performance status, tumor histology, and region.

The findings confirm the long-term efficacy of pembrolizumab, compared with platinum-based chemotherapy, demonstrate “consistent benefit in overall survival ... despite a crossover of 65%,” and show the first signs of efficacy with reexposure to pembrolizumab at the time of progression.

“This is work in progress; currently we have data from 10 [reexposed] patients, but what we do see is clinical activity even after [reexposure] to pembrolizumab, so we do see a stabilization of response to the disease in 70% of the patients, and 50% are ongoing.”

The findings highlight a new reality: “There are really some patients who have this disease as a chronic disease induced by immunotherapy.” Dr. Reck said.

KEYNOTE-024 was funded by Merck Sharp & Dohme. Dr. Reck reported receiving personal fees/honoraria for consultancy and lectures from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Merck Sharp & Dohme, MSD, Eli Lilly, Pfizer, AbbVie, Roche, and Novartis.

SOURCE: Reck M et al. WCLC 2019, Abstract OA14.01.

BARCELONA – First-line pembrolizumab provides a durable long-term overall survival (OS) benefit, compared with that of chemotherapy, in patients with advanced nonsquamous non–small cell lung cancer (NSCLC), according to 3-year data from the phase 3 Keynote-024 trial.

As previously reported, first-line treatment with the programmed death-1 (PD-1) inhibitor significantly improved progression-free survival (PFS) and OS, compared with those of platinum-based chemotherapy, and had fewer adverse events after a median of 11.2 months of follow-up in the open-label trial. In 305 patients with advanced NSCLC, high PD-L1 expression, and an absence of targetable epidermal growth factor or anaplastic lymphoma kinase gene alterations, median PFS was 10.3 months vs. 6.0 months, and estimated OS was 80.2% vs. 72.4% in the groups, respectively (hazard ratios, 0.50 and 0.60, respectively).

At 3 years after treatment initiation, median OS was 26.3 months vs. 14.2 months in patients treated with pembrolizumab or chemotherapy (HR, 0.65), respectively, and the OS rates were 43.7% and 24.9%, Martin Reck, MD, reported at the World Conference on Lung Cancer.

This was despite 98 of 151 patients assigned to chemotherapy crossing over to pembrolizumab, Dr. Reck, head of the department of thoracic oncology and the clinical trial department in the department of thoracic oncology at the Lung Clinic Grosshansdorf (Germany), noted at the conference, which was sponsored by the International Association for the Study of Lung Cancer.

Additionally, despite longer mean treatment duration in the pembrolizumab arm than in the chemotherapy arm (11.1 vs. 4.4 months), grade 3-5 treatment-related adverse events were less frequent with pembrolizumab than with chemotherapy (31.2% vs. 53.3%), he said.

Of 38 patients in the pembrolizumab arm who completed 2 years of therapy, 34 were alive at 3 years, and 31 (81.6%) had an objective response, including 2 who had a complete response. Median duration of response was not reached, and OS was 97.4%.

Grade 3-5 adverse events occurred in 5 (13.2%) of those patients; no fatal treatment-related adverse events occurred.

Of note, 7 of 10 patients who completed 2 years of treatment, but who subsequently progressed, experienced an objective response with a second course of pembrolizumab, and 8 remain alive, he said.

Patients in KEYNOTE-024 were randomized to receive 200 mg of pembrolizumab every 3 weeks for 2 years or investigator’s choice of platinum doublet for 4-6 cycles plus optional maintenance, with stratification by performance status, tumor histology, and region.

The findings confirm the long-term efficacy of pembrolizumab, compared with platinum-based chemotherapy, demonstrate “consistent benefit in overall survival ... despite a crossover of 65%,” and show the first signs of efficacy with reexposure to pembrolizumab at the time of progression.

“This is work in progress; currently we have data from 10 [reexposed] patients, but what we do see is clinical activity even after [reexposure] to pembrolizumab, so we do see a stabilization of response to the disease in 70% of the patients, and 50% are ongoing.”

The findings highlight a new reality: “There are really some patients who have this disease as a chronic disease induced by immunotherapy.” Dr. Reck said.

KEYNOTE-024 was funded by Merck Sharp & Dohme. Dr. Reck reported receiving personal fees/honoraria for consultancy and lectures from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Merck Sharp & Dohme, MSD, Eli Lilly, Pfizer, AbbVie, Roche, and Novartis.

SOURCE: Reck M et al. WCLC 2019, Abstract OA14.01.

BARCELONA – Final overall survival (OS) did not differ significantly among patients with stage IV squamous non–small cell lung carcinoma who were treated with either first-line atezolizumab + chemotherapy or chemotherapy alone in the phase 3 IMpower131 trial.

Sharon Worcester/MDedge News

Median OS in the intent-to-treat population was 14.2 months vs. 13.5 months with vs. without the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab, respectively (hazard ratio, 0.88), Federico Cappuzzo, MD, director of medical oncology at Azienda Unità Sanitaria Locale della Romagna-Ravenna, Italy, reported at the World Conference on Lung Cancer.

However, patients with high PD-L1 expression (14% and 13% of patients in the groups, respectively), experienced a clinically meaningful improvement in OS with atezolizumab + chemotherapy vs. chemotherapy alone (median of 23.4 vs. 10.2 months; HR, 0.48), Dr. Cappuzzo said at the conference, which was sponsored by the International Association for the Study of Lung Cancer.

“This means we had a reduction in the risk of death that was more than 50%,” he said, adding that no new or unexpected safety signals were reported.

IMpower131 randomized 1,021 patients with a median age of 65 years 1:1:1 to receive either atezolizumab (1,200 mg) + carboplatin (area under the curve 6) + paclitaxel (200 mg/m2) every 3 weeks, or atezolizumab + carboplatin + nab-paclitaxel (100 mg/m² every week), or carboplatin + nab-paclitaxel for four or six cycles. Patients in the first two arms (A and B) received atezolizumab maintenance therapy until loss of clinical benefit or progressive disease occurred, and those in latter arm (C) received best supportive care after completing the treatment cycles.

SOURCE: Cappuzzo F et al. WCLC 2019, Abstract OS14.02 .

BARCELONA – Final overall survival (OS) did not differ significantly among patients with stage IV squamous non–small cell lung carcinoma who were treated with either first-line atezolizumab + chemotherapy or chemotherapy alone in the phase 3 IMpower131 trial.

Sharon Worcester/MDedge News

Median OS in the intent-to-treat population was 14.2 months vs. 13.5 months with vs. without the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab, respectively (hazard ratio, 0.88), Federico Cappuzzo, MD, director of medical oncology at Azienda Unità Sanitaria Locale della Romagna-Ravenna, Italy, reported at the World Conference on Lung Cancer.

However, patients with high PD-L1 expression (14% and 13% of patients in the groups, respectively), experienced a clinically meaningful improvement in OS with atezolizumab + chemotherapy vs. chemotherapy alone (median of 23.4 vs. 10.2 months; HR, 0.48), Dr. Cappuzzo said at the conference, which was sponsored by the International Association for the Study of Lung Cancer.

“This means we had a reduction in the risk of death that was more than 50%,” he said, adding that no new or unexpected safety signals were reported.

IMpower131 randomized 1,021 patients with a median age of 65 years 1:1:1 to receive either atezolizumab (1,200 mg) + carboplatin (area under the curve 6) + paclitaxel (200 mg/m2) every 3 weeks, or atezolizumab + carboplatin + nab-paclitaxel (100 mg/m² every week), or carboplatin + nab-paclitaxel for four or six cycles. Patients in the first two arms (A and B) received atezolizumab maintenance therapy until loss of clinical benefit or progressive disease occurred, and those in latter arm (C) received best supportive care after completing the treatment cycles.

SOURCE: Cappuzzo F et al. WCLC 2019, Abstract OS14.02 .

BARCELONA – Final overall survival (OS) did not differ significantly among patients with stage IV squamous non–small cell lung carcinoma who were treated with either first-line atezolizumab + chemotherapy or chemotherapy alone in the phase 3 IMpower131 trial.

Sharon Worcester/MDedge News

Median OS in the intent-to-treat population was 14.2 months vs. 13.5 months with vs. without the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab, respectively (hazard ratio, 0.88), Federico Cappuzzo, MD, director of medical oncology at Azienda Unità Sanitaria Locale della Romagna-Ravenna, Italy, reported at the World Conference on Lung Cancer.

However, patients with high PD-L1 expression (14% and 13% of patients in the groups, respectively), experienced a clinically meaningful improvement in OS with atezolizumab + chemotherapy vs. chemotherapy alone (median of 23.4 vs. 10.2 months; HR, 0.48), Dr. Cappuzzo said at the conference, which was sponsored by the International Association for the Study of Lung Cancer.

“This means we had a reduction in the risk of death that was more than 50%,” he said, adding that no new or unexpected safety signals were reported.

IMpower131 randomized 1,021 patients with a median age of 65 years 1:1:1 to receive either atezolizumab (1,200 mg) + carboplatin (area under the curve 6) + paclitaxel (200 mg/m2) every 3 weeks, or atezolizumab + carboplatin + nab-paclitaxel (100 mg/m² every week), or carboplatin + nab-paclitaxel for four or six cycles. Patients in the first two arms (A and B) received atezolizumab maintenance therapy until loss of clinical benefit or progressive disease occurred, and those in latter arm (C) received best supportive care after completing the treatment cycles.

SOURCE: Cappuzzo F et al. WCLC 2019, Abstract OS14.02 .

BARCELONA – Tissue tumor mutational burden (TMB) was not significantly associated with treatment efficacy in patients with metastatic nonsquamous non–small cell lung cancer (NSCLC) in the phase 3 KEYNOTE-189 study and the phase 2 KEYNOTE-021 study.

In 293 patients with evaluable TMB data in KEYNOTE-189, including 207 who were treated with pembrolizumab plus chemotherapy and 86 who received placebo plus chemotherapy, TMB as a continuous variable showed no significant association with either overall survival (OS), progression-free survival (PFS), or objective response rate (ORR), Marina C. Garassino, MD, of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, reported at the World Conference on Lung Cancer.

Pembrolizumab plus chemotherapy improved OS both in patients with TMB of 175 mutations/exome and greater and in those with TMB of fewer than 175 mutations/exome (hazard ratio for OS, 0.64 for both), and similar results were seen for PFS and ORR, Dr. Garassino said at the conference, which is sponsored by the International Association for the Study of Lung Cancer. Similar results were also seen for those with tissue TMB of 150 mutations/exome or greater and those with fewer than 150 mutations/exome, she noted.

The double-blind KEYNOTE-189 study compared first-line pembrolizumab plus chemotherapy with placebo plus chemotherapy in 616 patients who were randomized 2:1 to the treatment arms, respectively, and showed that adding pembrolizumab to pemetrexed and platinum significantly improved OS (HR, 0.49), PFS (HR, 0.52), and ORR (47.6% vs. 18.9%). Benefit was observed in all analyzed subgroups, including patients with programmed death-ligand 1 (PD-L1) Tissue Polypeptide-specific (TPS) antigen of less than 1%, 1-49%, and 50% or greater, she noted.

In the current analysis, performed to assess the effect of tissue TMB on response rates, a similar benefit was seen in both TMB-high and -low subgroups.

“Our data suggest that tissue TMB may not help select patients who would have better outcomes with pembrolizumab plus pemetrexed and a platinum given as first-line therapy for metastatic nonsquamous NSCLC,” she concluded.

Similarly, an exploratory analysis of data from the open-label, phase 2 KEYNOTE-021 trial – the first trial to show the efficacy and safety of the anti–PD-1 immune checkpoint inhibitor pembrolizumab given with chemotherapy – showed no association between tissue TMB and OS, PFS, or ORR in 70 patients with metastatic nonsquamous NSCLC who were treated with either pembrolizumab plus carboplatin and pemetrexed or with carboplatin and pemetrexed alone, Corey Langer, MD, reported at the conference.

“As you’re well aware,TMB has been widely evaluated as a biomarker for immunotherapy in advanced [NSCLC] and may identify patients who are more likely to respond to immune checkpoint inhibitors,” said Dr. Langer, professor of medicine and director of thoracic surgery at the Hospital of the University of Pennsylvania, Philadelphia. “But we have very limited data on whether TMB is of any value as a biomarker for chemo, either alone or given with an immune checkpoint inhibitor.”

In this analysis, pembrolizumab plus chemotherapy was associated with a high response rate, regardless of tissue TMB status; in those with tissue TMB of 175 mutations/exome or greater and fewer than 175 mutations/exome, the response rates were 71% and 61%, respectively.

“So, tissue TMB assessed by whole-exome sequencing was not significantly associated with efficacy for pembro and combination pem-carbo, or for chemotherapy alone, for first-line treatment of patients with metastatic nonsquamous [NSCLC], nor was there any significant association with PD-L1 expression,” he said. “Obviously an analysis of much larger datasets is needed to assess whether the benefit of pembro plus chemo relative to chemo alone differs in patients with TMB-high or TMB-low tumors,” he said.

For now, tissue TMB should not be used – “at least not yet” – in therapeutic decision making, he said, adding that it is important to distinguish between blood TMB and tissue TMB because the latter “may be more reflective of the entire tumor.”

Dr. Langer noted that he still thinks TMB has a potential role.

“We just haven’t figured it out yet,” he said.

Both KEYNOTE-189 and KEYNOTE-021 were supported by Merck. Dr. Garassino and Dr. Langer reported relationships with several pharmaceutical companies.

SOURCES: Garassino MC et al. WCLC 2019, Abstract OA04.06; Langer C et al. WCLC 2019, Abstract OA04.05.

.

BARCELONA – Tissue tumor mutational burden (TMB) was not significantly associated with treatment efficacy in patients with metastatic nonsquamous non–small cell lung cancer (NSCLC) in the phase 3 KEYNOTE-189 study and the phase 2 KEYNOTE-021 study.

In 293 patients with evaluable TMB data in KEYNOTE-189, including 207 who were treated with pembrolizumab plus chemotherapy and 86 who received placebo plus chemotherapy, TMB as a continuous variable showed no significant association with either overall survival (OS), progression-free survival (PFS), or objective response rate (ORR), Marina C. Garassino, MD, of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, reported at the World Conference on Lung Cancer.

Pembrolizumab plus chemotherapy improved OS both in patients with TMB of 175 mutations/exome and greater and in those with TMB of fewer than 175 mutations/exome (hazard ratio for OS, 0.64 for both), and similar results were seen for PFS and ORR, Dr. Garassino said at the conference, which is sponsored by the International Association for the Study of Lung Cancer. Similar results were also seen for those with tissue TMB of 150 mutations/exome or greater and those with fewer than 150 mutations/exome, she noted.

The double-blind KEYNOTE-189 study compared first-line pembrolizumab plus chemotherapy with placebo plus chemotherapy in 616 patients who were randomized 2:1 to the treatment arms, respectively, and showed that adding pembrolizumab to pemetrexed and platinum significantly improved OS (HR, 0.49), PFS (HR, 0.52), and ORR (47.6% vs. 18.9%). Benefit was observed in all analyzed subgroups, including patients with programmed death-ligand 1 (PD-L1) Tissue Polypeptide-specific (TPS) antigen of less than 1%, 1-49%, and 50% or greater, she noted.

In the current analysis, performed to assess the effect of tissue TMB on response rates, a similar benefit was seen in both TMB-high and -low subgroups.

“Our data suggest that tissue TMB may not help select patients who would have better outcomes with pembrolizumab plus pemetrexed and a platinum given as first-line therapy for metastatic nonsquamous NSCLC,” she concluded.

Similarly, an exploratory analysis of data from the open-label, phase 2 KEYNOTE-021 trial – the first trial to show the efficacy and safety of the anti–PD-1 immune checkpoint inhibitor pembrolizumab given with chemotherapy – showed no association between tissue TMB and OS, PFS, or ORR in 70 patients with metastatic nonsquamous NSCLC who were treated with either pembrolizumab plus carboplatin and pemetrexed or with carboplatin and pemetrexed alone, Corey Langer, MD, reported at the conference.

“As you’re well aware,TMB has been widely evaluated as a biomarker for immunotherapy in advanced [NSCLC] and may identify patients who are more likely to respond to immune checkpoint inhibitors,” said Dr. Langer, professor of medicine and director of thoracic surgery at the Hospital of the University of Pennsylvania, Philadelphia. “But we have very limited data on whether TMB is of any value as a biomarker for chemo, either alone or given with an immune checkpoint inhibitor.”

In this analysis, pembrolizumab plus chemotherapy was associated with a high response rate, regardless of tissue TMB status; in those with tissue TMB of 175 mutations/exome or greater and fewer than 175 mutations/exome, the response rates were 71% and 61%, respectively.

“So, tissue TMB assessed by whole-exome sequencing was not significantly associated with efficacy for pembro and combination pem-carbo, or for chemotherapy alone, for first-line treatment of patients with metastatic nonsquamous [NSCLC], nor was there any significant association with PD-L1 expression,” he said. “Obviously an analysis of much larger datasets is needed to assess whether the benefit of pembro plus chemo relative to chemo alone differs in patients with TMB-high or TMB-low tumors,” he said.

For now, tissue TMB should not be used – “at least not yet” – in therapeutic decision making, he said, adding that it is important to distinguish between blood TMB and tissue TMB because the latter “may be more reflective of the entire tumor.”

Dr. Langer noted that he still thinks TMB has a potential role.

“We just haven’t figured it out yet,” he said.

Both KEYNOTE-189 and KEYNOTE-021 were supported by Merck. Dr. Garassino and Dr. Langer reported relationships with several pharmaceutical companies.

SOURCES: Garassino MC et al. WCLC 2019, Abstract OA04.06; Langer C et al. WCLC 2019, Abstract OA04.05.

.

BARCELONA – Tissue tumor mutational burden (TMB) was not significantly associated with treatment efficacy in patients with metastatic nonsquamous non–small cell lung cancer (NSCLC) in the phase 3 KEYNOTE-189 study and the phase 2 KEYNOTE-021 study.

In 293 patients with evaluable TMB data in KEYNOTE-189, including 207 who were treated with pembrolizumab plus chemotherapy and 86 who received placebo plus chemotherapy, TMB as a continuous variable showed no significant association with either overall survival (OS), progression-free survival (PFS), or objective response rate (ORR), Marina C. Garassino, MD, of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, reported at the World Conference on Lung Cancer.

Pembrolizumab plus chemotherapy improved OS both in patients with TMB of 175 mutations/exome and greater and in those with TMB of fewer than 175 mutations/exome (hazard ratio for OS, 0.64 for both), and similar results were seen for PFS and ORR, Dr. Garassino said at the conference, which is sponsored by the International Association for the Study of Lung Cancer. Similar results were also seen for those with tissue TMB of 150 mutations/exome or greater and those with fewer than 150 mutations/exome, she noted.

The double-blind KEYNOTE-189 study compared first-line pembrolizumab plus chemotherapy with placebo plus chemotherapy in 616 patients who were randomized 2:1 to the treatment arms, respectively, and showed that adding pembrolizumab to pemetrexed and platinum significantly improved OS (HR, 0.49), PFS (HR, 0.52), and ORR (47.6% vs. 18.9%). Benefit was observed in all analyzed subgroups, including patients with programmed death-ligand 1 (PD-L1) Tissue Polypeptide-specific (TPS) antigen of less than 1%, 1-49%, and 50% or greater, she noted.

In the current analysis, performed to assess the effect of tissue TMB on response rates, a similar benefit was seen in both TMB-high and -low subgroups.

“Our data suggest that tissue TMB may not help select patients who would have better outcomes with pembrolizumab plus pemetrexed and a platinum given as first-line therapy for metastatic nonsquamous NSCLC,” she concluded.

Similarly, an exploratory analysis of data from the open-label, phase 2 KEYNOTE-021 trial – the first trial to show the efficacy and safety of the anti–PD-1 immune checkpoint inhibitor pembrolizumab given with chemotherapy – showed no association between tissue TMB and OS, PFS, or ORR in 70 patients with metastatic nonsquamous NSCLC who were treated with either pembrolizumab plus carboplatin and pemetrexed or with carboplatin and pemetrexed alone, Corey Langer, MD, reported at the conference.

“As you’re well aware,TMB has been widely evaluated as a biomarker for immunotherapy in advanced [NSCLC] and may identify patients who are more likely to respond to immune checkpoint inhibitors,” said Dr. Langer, professor of medicine and director of thoracic surgery at the Hospital of the University of Pennsylvania, Philadelphia. “But we have very limited data on whether TMB is of any value as a biomarker for chemo, either alone or given with an immune checkpoint inhibitor.”

In this analysis, pembrolizumab plus chemotherapy was associated with a high response rate, regardless of tissue TMB status; in those with tissue TMB of 175 mutations/exome or greater and fewer than 175 mutations/exome, the response rates were 71% and 61%, respectively.

“So, tissue TMB assessed by whole-exome sequencing was not significantly associated with efficacy for pembro and combination pem-carbo, or for chemotherapy alone, for first-line treatment of patients with metastatic nonsquamous [NSCLC], nor was there any significant association with PD-L1 expression,” he said. “Obviously an analysis of much larger datasets is needed to assess whether the benefit of pembro plus chemo relative to chemo alone differs in patients with TMB-high or TMB-low tumors,” he said.

For now, tissue TMB should not be used – “at least not yet” – in therapeutic decision making, he said, adding that it is important to distinguish between blood TMB and tissue TMB because the latter “may be more reflective of the entire tumor.”

Dr. Langer noted that he still thinks TMB has a potential role.

“We just haven’t figured it out yet,” he said.

Both KEYNOTE-189 and KEYNOTE-021 were supported by Merck. Dr. Garassino and Dr. Langer reported relationships with several pharmaceutical companies.

SOURCES: Garassino MC et al. WCLC 2019, Abstract OA04.06; Langer C et al. WCLC 2019, Abstract OA04.05.

.

BARCELONA – Adding a blood microRNA (miRNA) assay to low-dose computed tomography (LDCT)–based lung cancer screening in heavy smokers bolsters lung cancer prevention efforts, according to findings from the prospective bioMILD trial.

Specifically, the addition of the miRNA assay appears to reduce unnecessary repeat LDCT scans based on individual risk profiles without adversely affecting lung cancer detection or mortality, Ugo Pastorino, MD, director of thoracic surgery at the Istituto Nazionale dei Tumori Foundation, Milan, reported at the World Conference on Lung Cancer.

Of 4,119 volunteers with a median age of 60 years and a median of 42 pack-years who were enrolled between January 2013 and March 2016, 2,384 (58%) were assigned a 3-year LDCT repeat according to their double-negative baseline LDCT and miRNA profile, whereas 1,526 (37%) with a single-positive screen (either a positive miRNA or indeterminate/positive LDCT) and 209 (5%) with double positive (both a positive miRNA and indeterminate/positive LDCT) were assigned to annual or shorter LDCT repeat.

After four screening runs, a total of 115 lung cancers were diagnosed. The cumulative lung cancer rates “were enormously different” in the 3 groups, despite similar group composition with respect to age, gender, and tobacco consumption (0.6% for double-negative screening, 3.8% for single-positive screening, and 20.1% for double-positive screening), and lung cancer mortality was 0.1%, 0.6%, and 3.8% in the groups, respectively, Dr. Pastorino said at the conference, which is sponsored by the International Association for the Study of Lung Cancer.

However, no significant differences were seen in the proportion of stage I lung cancers, resection rates, or interval cancer incidence in subjects sent to 3-year LDCT repeat, he noted.

The bioMILD trial was designed in the wake of the National Lung Screening Trial (NLST), which showed that three annual LDCT rounds for lung cancer screening reduced lung cancer mortality, and the Multicentric Italian Lung Detection (MILD) trial, which provided additional evidence that intervention beyond 5 years with annual or biennial rounds enhanced the benefit of screening.

Dr. Pastorino, the lead author on the MILD trial, previously reported that miRNA expression profiles in tumors and in normal lung tissue indicate aggressive lung cancer development and that specific miRNA signatures can be identified in plasma samples up to 2 years before spiral-CT detection of the disease.

The bioMILD trial tested the additional value of an miRNA assay at the time of LDCT.

Subjects were current (79%) or former heavy smokers, and 39% were women.

The findings suggest that adding the miRNA assay to LDCT for lung cancer screening is a “valuable and safe tool to assess individual risk profile and reduce unnecessary LDCT repeats in lung cancer screening,” Dr. Pastorino said.

“But what is more important for us [is that] the knowledge of individual biologic risk can improve the efficacy of screening, but can [also] guide prevention strategies because the problem in a heavy smoker is not to just detect lung cancer, it’s to reduce mortality,” he said at a press conference highlighting the findings. “And so, personalized prevention is a real option now, and that means diagnosis, but also preventive measures [such as] smoking cessation and chemoprevention.”

Invited discussant Harry J. de Koning, MD, PhD, professor of public health and screening evaluation at Erasmus Medical Center, Rotterdam, the Netherlands, noted that no other studies have evaluated screening intervals longer than 2 years, but he agreed that “reducing regular follow-up scans based on additional risk information is a way forward.”

However, the approach would increase costs, he said, adding that large, prospective, randomized, controlled trials are needed to confirm the safety of such approaches in nationwide programs.

Dr. Pastorino and Dr. de Koning each reported having no disclosures.

SOURCE: Pastorino U et al. WCLC 2019, Abstract PL02.04

BARCELONA – Adding a blood microRNA (miRNA) assay to low-dose computed tomography (LDCT)–based lung cancer screening in heavy smokers bolsters lung cancer prevention efforts, according to findings from the prospective bioMILD trial.

Specifically, the addition of the miRNA assay appears to reduce unnecessary repeat LDCT scans based on individual risk profiles without adversely affecting lung cancer detection or mortality, Ugo Pastorino, MD, director of thoracic surgery at the Istituto Nazionale dei Tumori Foundation, Milan, reported at the World Conference on Lung Cancer.

Of 4,119 volunteers with a median age of 60 years and a median of 42 pack-years who were enrolled between January 2013 and March 2016, 2,384 (58%) were assigned a 3-year LDCT repeat according to their double-negative baseline LDCT and miRNA profile, whereas 1,526 (37%) with a single-positive screen (either a positive miRNA or indeterminate/positive LDCT) and 209 (5%) with double positive (both a positive miRNA and indeterminate/positive LDCT) were assigned to annual or shorter LDCT repeat.

After four screening runs, a total of 115 lung cancers were diagnosed. The cumulative lung cancer rates “were enormously different” in the 3 groups, despite similar group composition with respect to age, gender, and tobacco consumption (0.6% for double-negative screening, 3.8% for single-positive screening, and 20.1% for double-positive screening), and lung cancer mortality was 0.1%, 0.6%, and 3.8% in the groups, respectively, Dr. Pastorino said at the conference, which is sponsored by the International Association for the Study of Lung Cancer.

However, no significant differences were seen in the proportion of stage I lung cancers, resection rates, or interval cancer incidence in subjects sent to 3-year LDCT repeat, he noted.

The bioMILD trial was designed in the wake of the National Lung Screening Trial (NLST), which showed that three annual LDCT rounds for lung cancer screening reduced lung cancer mortality, and the Multicentric Italian Lung Detection (MILD) trial, which provided additional evidence that intervention beyond 5 years with annual or biennial rounds enhanced the benefit of screening.

Dr. Pastorino, the lead author on the MILD trial, previously reported that miRNA expression profiles in tumors and in normal lung tissue indicate aggressive lung cancer development and that specific miRNA signatures can be identified in plasma samples up to 2 years before spiral-CT detection of the disease.

The bioMILD trial tested the additional value of an miRNA assay at the time of LDCT.

Subjects were current (79%) or former heavy smokers, and 39% were women.

The findings suggest that adding the miRNA assay to LDCT for lung cancer screening is a “valuable and safe tool to assess individual risk profile and reduce unnecessary LDCT repeats in lung cancer screening,” Dr. Pastorino said.

“But what is more important for us [is that] the knowledge of individual biologic risk can improve the efficacy of screening, but can [also] guide prevention strategies because the problem in a heavy smoker is not to just detect lung cancer, it’s to reduce mortality,” he said at a press conference highlighting the findings. “And so, personalized prevention is a real option now, and that means diagnosis, but also preventive measures [such as] smoking cessation and chemoprevention.”

Invited discussant Harry J. de Koning, MD, PhD, professor of public health and screening evaluation at Erasmus Medical Center, Rotterdam, the Netherlands, noted that no other studies have evaluated screening intervals longer than 2 years, but he agreed that “reducing regular follow-up scans based on additional risk information is a way forward.”

However, the approach would increase costs, he said, adding that large, prospective, randomized, controlled trials are needed to confirm the safety of such approaches in nationwide programs.

Dr. Pastorino and Dr. de Koning each reported having no disclosures.

SOURCE: Pastorino U et al. WCLC 2019, Abstract PL02.04

BARCELONA – Adding a blood microRNA (miRNA) assay to low-dose computed tomography (LDCT)–based lung cancer screening in heavy smokers bolsters lung cancer prevention efforts, according to findings from the prospective bioMILD trial.

Specifically, the addition of the miRNA assay appears to reduce unnecessary repeat LDCT scans based on individual risk profiles without adversely affecting lung cancer detection or mortality, Ugo Pastorino, MD, director of thoracic surgery at the Istituto Nazionale dei Tumori Foundation, Milan, reported at the World Conference on Lung Cancer.

Of 4,119 volunteers with a median age of 60 years and a median of 42 pack-years who were enrolled between January 2013 and March 2016, 2,384 (58%) were assigned a 3-year LDCT repeat according to their double-negative baseline LDCT and miRNA profile, whereas 1,526 (37%) with a single-positive screen (either a positive miRNA or indeterminate/positive LDCT) and 209 (5%) with double positive (both a positive miRNA and indeterminate/positive LDCT) were assigned to annual or shorter LDCT repeat.

After four screening runs, a total of 115 lung cancers were diagnosed. The cumulative lung cancer rates “were enormously different” in the 3 groups, despite similar group composition with respect to age, gender, and tobacco consumption (0.6% for double-negative screening, 3.8% for single-positive screening, and 20.1% for double-positive screening), and lung cancer mortality was 0.1%, 0.6%, and 3.8% in the groups, respectively, Dr. Pastorino said at the conference, which is sponsored by the International Association for the Study of Lung Cancer.

However, no significant differences were seen in the proportion of stage I lung cancers, resection rates, or interval cancer incidence in subjects sent to 3-year LDCT repeat, he noted.

The bioMILD trial was designed in the wake of the National Lung Screening Trial (NLST), which showed that three annual LDCT rounds for lung cancer screening reduced lung cancer mortality, and the Multicentric Italian Lung Detection (MILD) trial, which provided additional evidence that intervention beyond 5 years with annual or biennial rounds enhanced the benefit of screening.

Dr. Pastorino, the lead author on the MILD trial, previously reported that miRNA expression profiles in tumors and in normal lung tissue indicate aggressive lung cancer development and that specific miRNA signatures can be identified in plasma samples up to 2 years before spiral-CT detection of the disease.

The bioMILD trial tested the additional value of an miRNA assay at the time of LDCT.

Subjects were current (79%) or former heavy smokers, and 39% were women.

The findings suggest that adding the miRNA assay to LDCT for lung cancer screening is a “valuable and safe tool to assess individual risk profile and reduce unnecessary LDCT repeats in lung cancer screening,” Dr. Pastorino said.

“But what is more important for us [is that] the knowledge of individual biologic risk can improve the efficacy of screening, but can [also] guide prevention strategies because the problem in a heavy smoker is not to just detect lung cancer, it’s to reduce mortality,” he said at a press conference highlighting the findings. “And so, personalized prevention is a real option now, and that means diagnosis, but also preventive measures [such as] smoking cessation and chemoprevention.”

Invited discussant Harry J. de Koning, MD, PhD, professor of public health and screening evaluation at Erasmus Medical Center, Rotterdam, the Netherlands, noted that no other studies have evaluated screening intervals longer than 2 years, but he agreed that “reducing regular follow-up scans based on additional risk information is a way forward.”

However, the approach would increase costs, he said, adding that large, prospective, randomized, controlled trials are needed to confirm the safety of such approaches in nationwide programs.

Dr. Pastorino and Dr. de Koning each reported having no disclosures.

SOURCE: Pastorino U et al. WCLC 2019, Abstract PL02.04

BARCELONA – Mutations in the tumor suppressor KEAP1 or STK11 genes in patients with metastatic non–small cell lung cancer (mNSCLC) in the randomized, phase 3 MYSTIC trial experienced poorer outcomes than did patients without the mutations, according to an exploratory analysis of trial data.

Sharon Worcester/MDedge News

Mutations in ARID1a, however, were associated with improved overall survival (OS) among patients in the trial who were treated with durvalumab + tremelimumab.

Profiling of circulating tumor DNA from 943 evaluable baseline plasma specimens showed median OS of 7.4 vs. 12.9 months among 170 patients with KEAP1 mutations (m) vs. in 773 with KEAP1 wild type (hazard ratio, 1.64), and 6.8 vs. 12.6 months in patients with STK11m vs. 796 with STK11wt (HR, 1.52), Naiyer A. Rizvi, MD, the Price Family Professor of Medicine, director of Thoracic Oncology, and codirector of Cancer Immunotherapy at Columbia University Irving Medical Center, New York, reported at the World Conference on Lung Cancer.

Objective response rates (ORR) in the groups, respectively, were 17.6% vs. 27.7% for KEAP1m vs. KEAP1wt, and 16.3% vs. 27.6% for STK11m vs. STK11wt, Dr. Rizvi said at the conference, sponsored by the International Association for the Study of Lung Cancer.

This was regardless of MYSTIC trial treatment arm; the open-label, multicenter, global trial compared durvalumab monotherapy or durvalumab plus tremelimumab with platinum-based chemotherapy for the first-line treatment of patients with epidermal growth factor receptor and anaplastic lymphoma kinase wild-type, locally-advanced or metastatic NSCLC.

Mutations in the ARID1a gene, however, had no impact on OS (12.6 vs. 11.4 months in 114 vs. 829 patients with ARID1am vs. ARID1awt; HR, 0.94), and ORRs, respectively, were 35.1% vs. 24.6%.

When comparing outcomes by treatment arm, the ORRs with chemotherapy were 15.1% vs. 34% for KEAP1m vs. KEAP1wt, 12.2% vs. 33.6% for STK11m vs. STK1wt, and 28.1% vs. 31% for ARID1am vs. ARID1awt.

The ORRs in the durvalumab arm were 16.7% vs. 25.2% for KEAP1m vs. KEAP1st, 14.5% vs. 25.7% for STK11m vs. STK11wt and 25.6% vs. 23.4%, respectively, and in the durvalumab + tremelimumab arm they were 20.6% vs. 23.9% for KEAP1m vs. KEAP1wt, 21.6% vs. 23.6% for STK11m vs. STK11wt.

“The key finding here is really the ARID1a response,” Dr. Rizvi said, noting the “pretty impressive response rates” of 51.3% with ARID1am vs. 19.4% for ARID1awt.

The relationship between gene alterations and response to anti-programmed death-1 (PD-1) therapy with and without anti-CTLA-4 therapy is not well characterized. These findings, which suggest that KEAP1 and STK11 mutations are prognostic for OS in mNSCLC, and that ARID1am may be predictive of OS benefit in patients receiving durvalumab + tremelimumab, provide insights to the potential impact of specific mutations on response to immunotherapy, Dr. Rizvi said.

“STK11 and KEAP1 mutations ... are relatively common mutations – they are actually the third and fourth most common mutations in lung cancer after p53 and KRAS,” he said, adding that they influence outcomes and need to be factored in to analyses of outcomes in lung cancer. “ARID1am patients were about 10% of the population and they did particularly well with durvalumab and tremelimumab, and I think these exploratory analyses can help us think about how we use [tumor mutational burden] and outcomes among cancer patients in future trials.”

The MYSTIC trial was sponsored by AstraZeneca. Dr. Rizvi disclosed royalties related to intellectual property/patents filed by MSKCC and Personal Genome Diagnostics.

SOURCE: Rizvi N et al. WCLC 2019: Abstract OA04.07.

BARCELONA – Mutations in the tumor suppressor KEAP1 or STK11 genes in patients with metastatic non–small cell lung cancer (mNSCLC) in the randomized, phase 3 MYSTIC trial experienced poorer outcomes than did patients without the mutations, according to an exploratory analysis of trial data.

Sharon Worcester/MDedge News

Mutations in ARID1a, however, were associated with improved overall survival (OS) among patients in the trial who were treated with durvalumab + tremelimumab.

Profiling of circulating tumor DNA from 943 evaluable baseline plasma specimens showed median OS of 7.4 vs. 12.9 months among 170 patients with KEAP1 mutations (m) vs. in 773 with KEAP1 wild type (hazard ratio, 1.64), and 6.8 vs. 12.6 months in patients with STK11m vs. 796 with STK11wt (HR, 1.52), Naiyer A. Rizvi, MD, the Price Family Professor of Medicine, director of Thoracic Oncology, and codirector of Cancer Immunotherapy at Columbia University Irving Medical Center, New York, reported at the World Conference on Lung Cancer.

Objective response rates (ORR) in the groups, respectively, were 17.6% vs. 27.7% for KEAP1m vs. KEAP1wt, and 16.3% vs. 27.6% for STK11m vs. STK11wt, Dr. Rizvi said at the conference, sponsored by the International Association for the Study of Lung Cancer.

This was regardless of MYSTIC trial treatment arm; the open-label, multicenter, global trial compared durvalumab monotherapy or durvalumab plus tremelimumab with platinum-based chemotherapy for the first-line treatment of patients with epidermal growth factor receptor and anaplastic lymphoma kinase wild-type, locally-advanced or metastatic NSCLC.

Mutations in the ARID1a gene, however, had no impact on OS (12.6 vs. 11.4 months in 114 vs. 829 patients with ARID1am vs. ARID1awt; HR, 0.94), and ORRs, respectively, were 35.1% vs. 24.6%.

When comparing outcomes by treatment arm, the ORRs with chemotherapy were 15.1% vs. 34% for KEAP1m vs. KEAP1wt, 12.2% vs. 33.6% for STK11m vs. STK1wt, and 28.1% vs. 31% for ARID1am vs. ARID1awt.

The ORRs in the durvalumab arm were 16.7% vs. 25.2% for KEAP1m vs. KEAP1st, 14.5% vs. 25.7% for STK11m vs. STK11wt and 25.6% vs. 23.4%, respectively, and in the durvalumab + tremelimumab arm they were 20.6% vs. 23.9% for KEAP1m vs. KEAP1wt, 21.6% vs. 23.6% for STK11m vs. STK11wt.

“The key finding here is really the ARID1a response,” Dr. Rizvi said, noting the “pretty impressive response rates” of 51.3% with ARID1am vs. 19.4% for ARID1awt.

The relationship between gene alterations and response to anti-programmed death-1 (PD-1) therapy with and without anti-CTLA-4 therapy is not well characterized. These findings, which suggest that KEAP1 and STK11 mutations are prognostic for OS in mNSCLC, and that ARID1am may be predictive of OS benefit in patients receiving durvalumab + tremelimumab, provide insights to the potential impact of specific mutations on response to immunotherapy, Dr. Rizvi said.

“STK11 and KEAP1 mutations ... are relatively common mutations – they are actually the third and fourth most common mutations in lung cancer after p53 and KRAS,” he said, adding that they influence outcomes and need to be factored in to analyses of outcomes in lung cancer. “ARID1am patients were about 10% of the population and they did particularly well with durvalumab and tremelimumab, and I think these exploratory analyses can help us think about how we use [tumor mutational burden] and outcomes among cancer patients in future trials.”

The MYSTIC trial was sponsored by AstraZeneca. Dr. Rizvi disclosed royalties related to intellectual property/patents filed by MSKCC and Personal Genome Diagnostics.

SOURCE: Rizvi N et al. WCLC 2019: Abstract OA04.07.

BARCELONA – Mutations in the tumor suppressor KEAP1 or STK11 genes in patients with metastatic non–small cell lung cancer (mNSCLC) in the randomized, phase 3 MYSTIC trial experienced poorer outcomes than did patients without the mutations, according to an exploratory analysis of trial data.

Sharon Worcester/MDedge News

Mutations in ARID1a, however, were associated with improved overall survival (OS) among patients in the trial who were treated with durvalumab + tremelimumab.

Profiling of circulating tumor DNA from 943 evaluable baseline plasma specimens showed median OS of 7.4 vs. 12.9 months among 170 patients with KEAP1 mutations (m) vs. in 773 with KEAP1 wild type (hazard ratio, 1.64), and 6.8 vs. 12.6 months in patients with STK11m vs. 796 with STK11wt (HR, 1.52), Naiyer A. Rizvi, MD, the Price Family Professor of Medicine, director of Thoracic Oncology, and codirector of Cancer Immunotherapy at Columbia University Irving Medical Center, New York, reported at the World Conference on Lung Cancer.

Objective response rates (ORR) in the groups, respectively, were 17.6% vs. 27.7% for KEAP1m vs. KEAP1wt, and 16.3% vs. 27.6% for STK11m vs. STK11wt, Dr. Rizvi said at the conference, sponsored by the International Association for the Study of Lung Cancer.

This was regardless of MYSTIC trial treatment arm; the open-label, multicenter, global trial compared durvalumab monotherapy or durvalumab plus tremelimumab with platinum-based chemotherapy for the first-line treatment of patients with epidermal growth factor receptor and anaplastic lymphoma kinase wild-type, locally-advanced or metastatic NSCLC.

Mutations in the ARID1a gene, however, had no impact on OS (12.6 vs. 11.4 months in 114 vs. 829 patients with ARID1am vs. ARID1awt; HR, 0.94), and ORRs, respectively, were 35.1% vs. 24.6%.

When comparing outcomes by treatment arm, the ORRs with chemotherapy were 15.1% vs. 34% for KEAP1m vs. KEAP1wt, 12.2% vs. 33.6% for STK11m vs. STK1wt, and 28.1% vs. 31% for ARID1am vs. ARID1awt.

The ORRs in the durvalumab arm were 16.7% vs. 25.2% for KEAP1m vs. KEAP1st, 14.5% vs. 25.7% for STK11m vs. STK11wt and 25.6% vs. 23.4%, respectively, and in the durvalumab + tremelimumab arm they were 20.6% vs. 23.9% for KEAP1m vs. KEAP1wt, 21.6% vs. 23.6% for STK11m vs. STK11wt.

“The key finding here is really the ARID1a response,” Dr. Rizvi said, noting the “pretty impressive response rates” of 51.3% with ARID1am vs. 19.4% for ARID1awt.

The relationship between gene alterations and response to anti-programmed death-1 (PD-1) therapy with and without anti-CTLA-4 therapy is not well characterized. These findings, which suggest that KEAP1 and STK11 mutations are prognostic for OS in mNSCLC, and that ARID1am may be predictive of OS benefit in patients receiving durvalumab + tremelimumab, provide insights to the potential impact of specific mutations on response to immunotherapy, Dr. Rizvi said.

“STK11 and KEAP1 mutations ... are relatively common mutations – they are actually the third and fourth most common mutations in lung cancer after p53 and KRAS,” he said, adding that they influence outcomes and need to be factored in to analyses of outcomes in lung cancer. “ARID1am patients were about 10% of the population and they did particularly well with durvalumab and tremelimumab, and I think these exploratory analyses can help us think about how we use [tumor mutational burden] and outcomes among cancer patients in future trials.”

The MYSTIC trial was sponsored by AstraZeneca. Dr. Rizvi disclosed royalties related to intellectual property/patents filed by MSKCC and Personal Genome Diagnostics.

SOURCE: Rizvi N et al. WCLC 2019: Abstract OA04.07.

BARCELONA – Molecular testing to guide treatment in patients with lung cancer remains underused, and awareness of related evidence-based guidelines is suboptimal, results of an international survey suggest.

Sharon Worcester/ MDedge News

Overall, 61% of the 2,537 respondents from 102 countries and across multiple relevant medical specialties reported that molecular testing rates in their country were less than 50%, with the lowest rates reported in Latin America. And 33% of those requesting molecular testing said they were unaware of the most updated guidelines supporting the use of such testing in lung cancer, Matthew Smeltzer, PhD, of the University of Memphis (Tenn.) reported during a press conference at the World Conference on Lung Cancer.

The findings from the International Association for the Study of Lung Cancer (IASLC) Global Survey on Molecular Testing in Lung Cancer also showed that 41% of respondents who perform or interpret molecular testing assays report being dissatisfied with the conditions of molecular testing in their country, 17% said they feel that patients are not satisfied, and 35% said they aren’t sure about the state of testing in their country.

Specific concerns reported by respondents included trouble understanding results, the time it takes to receive the results, and the reliability of samples.

The top five barriers to molecular testing included cost, quality, access, awareness, and time, Dr. Smeltzer said at the meeting which is sponsored by the IASLC.

“These five were the same five top barriers in each region of the world,” he said, noting that the ordering of the barriers differed somewhat among regions.

The survey included a seven-question introduction, with 32 additional questions for respondents who request tests and treat patients, 45 questions on performing and interpreting assays, and 24 questions on tissue acquisition. Additionally, all respondents were asked to list barriers that impede their country’s ability to offer molecular testing.

“I’d say we got a pretty good geographic distribution of responses; 56% of these responses were from developing countries, 44% from developed countries,” he said, noting that medical oncologists constituted the highest percentage of respondents, followed by pulmonologists, thoracic surgeons, pathologists, and other scientists.

When asked specifically what would prompt molecular testing, respondents most often listed adenocarcinoma, never-smoker status, female gender, and young age, Dr. Smeltzer said.

“Overall, we’re still finding that many in the lung cancer community are not satisfied with the current state of molecular testing. We’ve got suboptimal awareness of the evidence-based guidelines. We have barriers that remain to molecular testing, which we’ve identified, and [we’re] recommending continuous education around molecular testing, and that should be intensified on a national and international level to ensure that patients receive optimal therapy,” he concluded.

The IASLC survey was funded by AstraZeneca. Dr. Smeltzer reported receiving research support from the Bristol Myers Squibb Foundation.

[email protected]

BARCELONA – Molecular testing to guide treatment in patients with lung cancer remains underused, and awareness of related evidence-based guidelines is suboptimal, results of an international survey suggest.

Sharon Worcester/ MDedge News

Overall, 61% of the 2,537 respondents from 102 countries and across multiple relevant medical specialties reported that molecular testing rates in their country were less than 50%, with the lowest rates reported in Latin America. And 33% of those requesting molecular testing said they were unaware of the most updated guidelines supporting the use of such testing in lung cancer, Matthew Smeltzer, PhD, of the University of Memphis (Tenn.) reported during a press conference at the World Conference on Lung Cancer.

The findings from the International Association for the Study of Lung Cancer (IASLC) Global Survey on Molecular Testing in Lung Cancer also showed that 41% of respondents who perform or interpret molecular testing assays report being dissatisfied with the conditions of molecular testing in their country, 17% said they feel that patients are not satisfied, and 35% said they aren’t sure about the state of testing in their country.

Specific concerns reported by respondents included trouble understanding results, the time it takes to receive the results, and the reliability of samples.

The top five barriers to molecular testing included cost, quality, access, awareness, and time, Dr. Smeltzer said at the meeting which is sponsored by the IASLC.

“These five were the same five top barriers in each region of the world,” he said, noting that the ordering of the barriers differed somewhat among regions.

The survey included a seven-question introduction, with 32 additional questions for respondents who request tests and treat patients, 45 questions on performing and interpreting assays, and 24 questions on tissue acquisition. Additionally, all respondents were asked to list barriers that impede their country’s ability to offer molecular testing.

“I’d say we got a pretty good geographic distribution of responses; 56% of these responses were from developing countries, 44% from developed countries,” he said, noting that medical oncologists constituted the highest percentage of respondents, followed by pulmonologists, thoracic surgeons, pathologists, and other scientists.

When asked specifically what would prompt molecular testing, respondents most often listed adenocarcinoma, never-smoker status, female gender, and young age, Dr. Smeltzer said.

“Overall, we’re still finding that many in the lung cancer community are not satisfied with the current state of molecular testing. We’ve got suboptimal awareness of the evidence-based guidelines. We have barriers that remain to molecular testing, which we’ve identified, and [we’re] recommending continuous education around molecular testing, and that should be intensified on a national and international level to ensure that patients receive optimal therapy,” he concluded.

The IASLC survey was funded by AstraZeneca. Dr. Smeltzer reported receiving research support from the Bristol Myers Squibb Foundation.

[email protected]

BARCELONA – Molecular testing to guide treatment in patients with lung cancer remains underused, and awareness of related evidence-based guidelines is suboptimal, results of an international survey suggest.

Sharon Worcester/ MDedge News

Overall, 61% of the 2,537 respondents from 102 countries and across multiple relevant medical specialties reported that molecular testing rates in their country were less than 50%, with the lowest rates reported in Latin America. And 33% of those requesting molecular testing said they were unaware of the most updated guidelines supporting the use of such testing in lung cancer, Matthew Smeltzer, PhD, of the University of Memphis (Tenn.) reported during a press conference at the World Conference on Lung Cancer.

The findings from the International Association for the Study of Lung Cancer (IASLC) Global Survey on Molecular Testing in Lung Cancer also showed that 41% of respondents who perform or interpret molecular testing assays report being dissatisfied with the conditions of molecular testing in their country, 17% said they feel that patients are not satisfied, and 35% said they aren’t sure about the state of testing in their country.

Specific concerns reported by respondents included trouble understanding results, the time it takes to receive the results, and the reliability of samples.

The top five barriers to molecular testing included cost, quality, access, awareness, and time, Dr. Smeltzer said at the meeting which is sponsored by the IASLC.

“These five were the same five top barriers in each region of the world,” he said, noting that the ordering of the barriers differed somewhat among regions.

The survey included a seven-question introduction, with 32 additional questions for respondents who request tests and treat patients, 45 questions on performing and interpreting assays, and 24 questions on tissue acquisition. Additionally, all respondents were asked to list barriers that impede their country’s ability to offer molecular testing.

“I’d say we got a pretty good geographic distribution of responses; 56% of these responses were from developing countries, 44% from developed countries,” he said, noting that medical oncologists constituted the highest percentage of respondents, followed by pulmonologists, thoracic surgeons, pathologists, and other scientists.

When asked specifically what would prompt molecular testing, respondents most often listed adenocarcinoma, never-smoker status, female gender, and young age, Dr. Smeltzer said.

“Overall, we’re still finding that many in the lung cancer community are not satisfied with the current state of molecular testing. We’ve got suboptimal awareness of the evidence-based guidelines. We have barriers that remain to molecular testing, which we’ve identified, and [we’re] recommending continuous education around molecular testing, and that should be intensified on a national and international level to ensure that patients receive optimal therapy,” he concluded.

The IASLC survey was funded by AstraZeneca. Dr. Smeltzer reported receiving research support from the Bristol Myers Squibb Foundation.

[email protected]

BARCELONA – All cancer patients should be screened for tobacco use and advised about the benefits of tobacco cessation, and evidence-based tobacco cessation assistance should be provided to those who continue using tobacco, according to a new declaration from the International Association for the Study of Lung Cancer (IASLC).

Sharon Worcester/ MDedge News

Such assistance should be “routinely and integrally incorporated into multidisciplinary cancer care for the patients and their family members,” according to the declaration, which was developed by the IASLC Tobacco Control and Smoking Cessation Committee in part to increase physician involvement in tobacco control and was officially released at the World Conference on Lung Cancer.

“The consequences of smoking continuation by cancer patients and cancer survivors are many,” presenting author Jacek Jassem, MD, PhD, professor and head of the department of oncology and radiotherapy at the Medical University of Gdansk (Poland), said during a press conference at the meeting, which is sponsored by the IASLC.

Smoking after a cancer diagnosis increases cancer-related and overall mortality, the risk of developing additional cancers, and the risk of treatment toxicity, he explained.

“And of course [continued smoking is] associated with much higher treatment costs, mostly due to complications,” he added.

The IASLC addresses both the challenges and opportunities associated with tobacco cessation, including the fact that most cancer patients who smoke continue to do so during and after treatment and that health care providers often don’t provide patients with cessation assistance to help them quit.

In addition to the screening and tobacco cessation assistance recommendations, the declaration also states the following:

• Educational programs regarding cancer management should include tobacco cessation training, empathetic communication around the history of tobacco use and cessation, and utilization of existing evidence-based tobacco cessation resources.
• Smoking cessation counseling and treatment should be a reimbursable service.
• Smoking status, both initially and during the study, should be a required data element for all prospective clinical studies.
• Clinical trials of patients with cancer should consider designs that could also determine the most effective tobacco cessation interventions.

Dr. Jassem is on the speakers bureau for MSD, Takeda, BMS, Astra-Zeneca, and Pfizer.

[email protected]

BARCELONA – All cancer patients should be screened for tobacco use and advised about the benefits of tobacco cessation, and evidence-based tobacco cessation assistance should be provided to those who continue using tobacco, according to a new declaration from the International Association for the Study of Lung Cancer (IASLC).

Sharon Worcester/ MDedge News

Such assistance should be “routinely and integrally incorporated into multidisciplinary cancer care for the patients and their family members,” according to the declaration, which was developed by the IASLC Tobacco Control and Smoking Cessation Committee in part to increase physician involvement in tobacco control and was officially released at the World Conference on Lung Cancer.

“The consequences of smoking continuation by cancer patients and cancer survivors are many,” presenting author Jacek Jassem, MD, PhD, professor and head of the department of oncology and radiotherapy at the Medical University of Gdansk (Poland), said during a press conference at the meeting, which is sponsored by the IASLC.

Smoking after a cancer diagnosis increases cancer-related and overall mortality, the risk of developing additional cancers, and the risk of treatment toxicity, he explained.

“And of course [continued smoking is] associated with much higher treatment costs, mostly due to complications,” he added.

The IASLC addresses both the challenges and opportunities associated with tobacco cessation, including the fact that most cancer patients who smoke continue to do so during and after treatment and that health care providers often don’t provide patients with cessation assistance to help them quit.

In addition to the screening and tobacco cessation assistance recommendations, the declaration also states the following:

• Educational programs regarding cancer management should include tobacco cessation training, empathetic communication around the history of tobacco use and cessation, and utilization of existing evidence-based tobacco cessation resources.
• Smoking cessation counseling and treatment should be a reimbursable service.
• Smoking status, both initially and during the study, should be a required data element for all prospective clinical studies.
• Clinical trials of patients with cancer should consider designs that could also determine the most effective tobacco cessation interventions.

Dr. Jassem is on the speakers bureau for MSD, Takeda, BMS, Astra-Zeneca, and Pfizer.

[email protected]

BARCELONA – All cancer patients should be screened for tobacco use and advised about the benefits of tobacco cessation, and evidence-based tobacco cessation assistance should be provided to those who continue using tobacco, according to a new declaration from the International Association for the Study of Lung Cancer (IASLC).

Sharon Worcester/ MDedge News

Such assistance should be “routinely and integrally incorporated into multidisciplinary cancer care for the patients and their family members,” according to the declaration, which was developed by the IASLC Tobacco Control and Smoking Cessation Committee in part to increase physician involvement in tobacco control and was officially released at the World Conference on Lung Cancer.

“The consequences of smoking continuation by cancer patients and cancer survivors are many,” presenting author Jacek Jassem, MD, PhD, professor and head of the department of oncology and radiotherapy at the Medical University of Gdansk (Poland), said during a press conference at the meeting, which is sponsored by the IASLC.

Smoking after a cancer diagnosis increases cancer-related and overall mortality, the risk of developing additional cancers, and the risk of treatment toxicity, he explained.

“And of course [continued smoking is] associated with much higher treatment costs, mostly due to complications,” he added.

The IASLC addresses both the challenges and opportunities associated with tobacco cessation, including the fact that most cancer patients who smoke continue to do so during and after treatment and that health care providers often don’t provide patients with cessation assistance to help them quit.

In addition to the screening and tobacco cessation assistance recommendations, the declaration also states the following:

• Educational programs regarding cancer management should include tobacco cessation training, empathetic communication around the history of tobacco use and cessation, and utilization of existing evidence-based tobacco cessation resources.
• Smoking cessation counseling and treatment should be a reimbursable service.
• Smoking status, both initially and during the study, should be a required data element for all prospective clinical studies.
• Clinical trials of patients with cancer should consider designs that could also determine the most effective tobacco cessation interventions.

Dr. Jassem is on the speakers bureau for MSD, Takeda, BMS, Astra-Zeneca, and Pfizer.

[email protected]