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Lurbinectedin induces response in small cell lung cancer

CHICAGO — Lurbinectedin improved overall response rate and survival outcomes for patients with small cell lung cancer, according to findings from the phase 2 BASKET trial presented at ASCO Annual Meeting.

Topotecan has been the only treatment approved for second-line, platinum-sensitive small cell lung cancer for over 2 decades. However, the agent has modest clinical benefit, with an ORR ranging from 5% to 24% and median OS of 6 to 8 months.

“Lurbinectedin is an active single-agent treatment alternative for second-line small cell lung cancer where, until now, no progress has been made for more than 2 decades. Lurbinectedin has now emerged as a potential new treatment alternative for these patients,” Luis G. Paz-Ares, MD, PhD, chair of the department of medical oncology at Hospital 12 de Octubre, associate professor at Universidad Complutense, and head of the lung cancer unit at the National Oncology Research Center in Madrid, said during the presentation.

A previous phase 1/phase 2 trial showed the combination of lurbinectedin (PM1183, PharmaMar) — a RNA polymerase II inhibitor — and doxorubicin induced a 37% ORR rate with a 5.2-month duration of response among patients with small cell lung cancer.

In March, the FDA granted orphan drug status to lurbinectedin.

For the current trial, investigators assessed 3.2 mg/m² lurbinectedin IV every 3 weeks among 105 patients (median age, 60 years; 60% men) with small cell lung cancer. Forty-three percent of patients (n = 45) had a chemotherapy-free interval of less than 90 days, which researchers considered resistant disease. Fifty-seven percent (n = 60) had a chemotherapy-interval of 90 days or longer, indicating sensitive disease.

Patients received a median four cycles (range, 1-24) of lurbinectedin therapy.

ORR served as the primary endpoint. Secondary endpoints included PFS and OS.

Median follow-up was 17.1 months.

ORR was 35.2% (95% CI, 26.2-45.2) among all patients, 45% (95% CI, 32.1-58.4) among those with sensitive disease, and 22.2% (95% CI, 11.2-37.1) among those with resistant disease.

Overall, 65% of patients showed some degree of tumor shrinkage on trial.

Median PFS was 3.9 (95% CI, 2.6-4.6) months among all patients, 4.6 months (95% CI, 3-6.5) among those with sensitive disease, and 2.6 months (95% CI, 1.3-3.9) among those with resistant disease. Median OS was 9.3 months (95% CI, 6.3-11.8) among all patients, 11.9 months (95% CI, 9.7-16.2) among those with sensitive disease, and 5 months (95% CI, 4.1-6.3) among those with resistant disease.

Moreover, the overall disease control rate was 68.6% (95% CI, 58.5-77.3), including 81.7% (95% CI, 69.6-90.5) among those with sensitive disease and 51.1% (95% CI, 35.8-66.3) among those with resistant disease.

Median duration of response was 5.3 months (95% CI, 4.1-6.4) among all patients, 6.2 months (95% CI, 3.5-7.3) among those with sensitive disease, and 4.7 months (95% CI, 2.6-5.6) among those with resistant disease.

The most common grade 3 or higher adverse events included febrile neutropenia (4.8%), anemia (6.7%) and thrombocytopenia (4.8%). – by Jennifer Southall

Reference:

Paz-Ares, et al. Abstract 8506. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.

Disclosures: Paz-Ares reports honoraria from Adacap, Amgen, AstraZeneca, Bayer, Blueprint, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Incyte, Ipsen, Merck, Merck Sharpe & Dohme, Novartis, Pfizer, PharmaMar, Roche, Sanofi, Servier, and Sysmex; research grants to his institution from AstraZeneca, Bristol-Myers Squibb, Merck Sharpe & Dohme and Pfizer; serving on the board for Genomica; and being a co-founder of Altum Sequencing. Please see the abstract for all other authors’ relevant financial disclosures.

CHICAGO — Lurbinectedin improved overall response rate and survival outcomes for patients with small cell lung cancer, according to findings from the phase 2 BASKET trial presented at ASCO Annual Meeting.

Topotecan has been the only treatment approved for second-line, platinum-sensitive small cell lung cancer for over 2 decades. However, the agent has modest clinical benefit, with an ORR ranging from 5% to 24% and median OS of 6 to 8 months.

“Lurbinectedin is an active single-agent treatment alternative for second-line small cell lung cancer where, until now, no progress has been made for more than 2 decades. Lurbinectedin has now emerged as a potential new treatment alternative for these patients,” Luis G. Paz-Ares, MD, PhD, chair of the department of medical oncology at Hospital 12 de Octubre, associate professor at Universidad Complutense, and head of the lung cancer unit at the National Oncology Research Center in Madrid, said during the presentation.

A previous phase 1/phase 2 trial showed the combination of lurbinectedin (PM1183, PharmaMar) — a RNA polymerase II inhibitor — and doxorubicin induced a 37% ORR rate with a 5.2-month duration of response among patients with small cell lung cancer.

In March, the FDA granted orphan drug status to lurbinectedin.

For the current trial, investigators assessed 3.2 mg/m² lurbinectedin IV every 3 weeks among 105 patients (median age, 60 years; 60% men) with small cell lung cancer. Forty-three percent of patients (n = 45) had a chemotherapy-free interval of less than 90 days, which researchers considered resistant disease. Fifty-seven percent (n = 60) had a chemotherapy-interval of 90 days or longer, indicating sensitive disease.

Patients received a median four cycles (range, 1-24) of lurbinectedin therapy.

ORR served as the primary endpoint. Secondary endpoints included PFS and OS.

Median follow-up was 17.1 months.

ORR was 35.2% (95% CI, 26.2-45.2) among all patients, 45% (95% CI, 32.1-58.4) among those with sensitive disease, and 22.2% (95% CI, 11.2-37.1) among those with resistant disease.

Overall, 65% of patients showed some degree of tumor shrinkage on trial.

Median PFS was 3.9 (95% CI, 2.6-4.6) months among all patients, 4.6 months (95% CI, 3-6.5) among those with sensitive disease, and 2.6 months (95% CI, 1.3-3.9) among those with resistant disease. Median OS was 9.3 months (95% CI, 6.3-11.8) among all patients, 11.9 months (95% CI, 9.7-16.2) among those with sensitive disease, and 5 months (95% CI, 4.1-6.3) among those with resistant disease.

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Moreover, the overall disease control rate was 68.6% (95% CI, 58.5-77.3), including 81.7% (95% CI, 69.6-90.5) among those with sensitive disease and 51.1% (95% CI, 35.8-66.3) among those with resistant disease.

Median duration of response was 5.3 months (95% CI, 4.1-6.4) among all patients, 6.2 months (95% CI, 3.5-7.3) among those with sensitive disease, and 4.7 months (95% CI, 2.6-5.6) among those with resistant disease.

The most common grade 3 or higher adverse events included febrile neutropenia (4.8%), anemia (6.7%) and thrombocytopenia (4.8%). – by Jennifer Southall

Reference:

Paz-Ares, et al. Abstract 8506. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.

Disclosures: Paz-Ares reports honoraria from Adacap, Amgen, AstraZeneca, Bayer, Blueprint, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Incyte, Ipsen, Merck, Merck Sharpe & Dohme, Novartis, Pfizer, PharmaMar, Roche, Sanofi, Servier, and Sysmex; research grants to his institution from AstraZeneca, Bristol-Myers Squibb, Merck Sharpe & Dohme and Pfizer; serving on the board for Genomica; and being a co-founder of Altum Sequencing. Please see the abstract for all other authors’ relevant financial disclosures.

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