Docetaxel Plus Ramucirumab After Standard Frontline Treatment Elicits Responses in NSCLC

The use of docetaxel and ramucirumab (Cyramza) yielded antitumor activity and showcased a manageable safety profile in patients with non–small cell lung cancer (NSCLC) who progressed on platinum-based chemotherapy and immune checkpoint inhibitors, according to data from the phase 2 SCORPION study (jCRTs041190077) presented at the 2023 European Lung Cancer Congress.

The doublet elicited an overall response rate (ORR) of 34.4% (80% CI, 23.1-47.2%; 95% CI, 18.6%-53.2%) in evaluable patients (n = 32), meeting the primary end point of the trial. Moreover, the disease control rate in these patients was 81.3% (95% CI, 63.6%-92.8%).

Notably, 4 patients did not meet criteria for the safety analysis of the trial, as the last dose of anticancer drug was required to be at least 28 days before registration. With these patients excluded, the ORR with the combination was 32.1% (80% CI, 20.4%-45.9%; n = 28).

Additionally, patients who responded to previous treatment with chemoimmunotherapy (n = 15) achieved an ORR of 40.0% with the doublet; those who did not respond to prior treatment (n = 17) had a lower ORR of 29.4%.

“Docetaxel plus ramucirumab demonstrated encouraging antitumor activity with a manageable safety profile in patients who have failed with front-line platinum-based chemotherapy plus immune checkpoint inhibitors,” lead study author Reiko Matsuzawa, MD, of Nagoya University Graduate School of Medicine, in Nagoya, Japan, and colleagues, wrote in a poster on the data.

Platinum-based chemotherapy with immune checkpoint inhibitors serves as the frontline standard of care for patients with NSCLC. Findings from retrospective studies suggest that increased efficacy is achievable with the use of docetaxel plus ramucirumab following single-agent checkpoint inhibition. However, the safety profile of this approach has not yet been confirmed.

The single-arm, multicenter, open-label phase 2 trial enrolled patients with stage IV or recurrent NSCLC whose disease progressed on or after platinum-based chemotherapy and immune checkpoint inhibitors. Patients were enrolled if they were at least of 20 years of age, had an ECOG performance status of 0 or 1, and a minimum of 1 measurable lesion by RECIST v1.1 criteria. Patients also needed to have acceptable hematologic and organ function.

If patients underwent any major surgical procedure within 28 days of the trial; had radiographic evidence of intratumor cavitation, irrespective of tumor histology; a history of severe thromboembolic events within 3 months of the trial; or a history of hemoptysis within 2 months prior to registration, they were excluded. Patients also could not have a medication history comprised of antiplatelet, anti-vitamin K, or anticoagulation therapy within 14 days of the study, nor could they have uncontrolled hypertension of greater than or equal to 150/90 mmHg. Other exclusion criteria included having significant bleeding disorders or grade 3 or 4 gastrointestinal bleeding within 3 months of enrollment.

Study participants received 60 mg/m² of docetaxel plus 10 mg/kg of ramucirumab on day 1, followed by 3.6 mg of pegfilgrastim (Neulasta) on day 2, every 3 weeks. Treatment continued until patients experienced disease progression or intolerable toxicity.

In addition to ORR serving as the trial’s primary end point, secondary end points comprised overall survival (OS), progression-free survival (PFS), and safety.

Patients were recruited between January 2020 and August 2021 and were enrolled at 8 institutions. Among the 32 patients who comprised the efficacy analysis, the median age was 66 years (range, 42-79), with 47% of patients under 65 years of age. The majority of patients were male (78%). Regarding ECOG performance status, 59% of patients had a status of 0, and 41% of patients had a status of 1. Seventy-five percent of patients were ever smokers. In terms of histologic subtype, 88% of patients had nonsquamous disease and the remainder had squamous disease.

Regarding EGFR mutational status, 75% of patients had wild-type disease, 22% had mutant disease, and 3% of patients had unknown status. Forty-seven percent of patients experienced a complete or partial response as their best response to previous immune checkpoint inhibitor combination therapy, and 53% had stable disease or disease progression. Additionally, 37% of patients received a previous taxane, 25% received prior bevacizumab (Avastin), and 16% received prior radiation. Seventy-eight percent of patients received their last immune checkpoint inhibitor in fewer than 60 days prior to enrollment.

Additional data showed that in evaluable patients (n = 32), the median PFS with the regimen was 6.5 months (95% CI, 4.4-8.2); the estimated PFS rates at 6 months and 12 months were 53.1% and 21.9%, respectively. Moreover, the median OS was 17.5 months (95% CI, 11.3-not reached [NR]), with estimated 6- and 12-month rates of 68.5% and 49.0%, respectively. The median duration of response with the combination was 5.1 months (95% CI, 2.9-11.2; n = 11). Half of patients who responded to treatment were anticipated to still be in response at 6 months; the estimated 12-month DOR rate was 10.0%.

In the 15 patients who responded to prior chemoimmunotherapy, the median PFS with the doublet was 6.9 months (95% CI, 3.0-12.6); in this group, the estimated PFS rates were 60.0% at 6 months and 33.3% at 12 months. In these patients, the median OS was NR (95% CI, 8.0-NR); the estimated OS rate was 65.2% for both 6 months and 12 months. The median DOR in this group was 11.1 months (95% CI, 4.9-NR), with 60% of patients expected to still be in response to treatment at 6 months.

Those who did not respond to prior chemoimmunotherapy (n = 17), experienced a median PFS of 6.0 months (95% CI, 4.2-8.5) with docetaxel plus ramucirumab; here, the estimated 6- and 12-month PFS rates were 47.1% and 11.8%, respectively. In this group, the median OS was 15.8 months (95% CI, 7.7-NR); the estimated OS rates at 6 months and 12 months were 70.6% and 34.9%, respectively. The median DOR in this subset was 4.6 months (95% CI, 2.9-NR) with the doublet with 40% of patients estimated to still be in response to treatment at 12 months.

A total of 33 patients were included in the safety set; all patients experienced a toxicity of any grade and 58% reported a grade 3 or higher adverse effect (AE). The most common grade 3 or higher AEs included neutropenia (24%), anorexia (15%), hyponatremia (9%), pneumonitis (9%), febrile neutropenia (9%), edema limbs (6%), anemia (6%), bleeding or hemorrhage (6%), hypertension (6%), stomatitis (3%), increased alanine aminotransferase (3%), weight gain (3%), decreased white blood cell count (3%), thrombocytopenia (3%), pulmonary hemorrhage events (3%), gastrointestinal hemorrhage (3%), and proteinuria (3%).

Reference

Matsuzawa R, Morise M, Ito K, et al. Multi-center, phase II study of docetaxel (DTX) plus ramucirumab (RAM) following platinum-based chemotherapy plus ICIs in patients with NSCLC: SCORPION study. Presented at: 2023 European Lung Cancer Congress; March 29-April 1, 2023; Copenhagen, Denmark. Poster 46P.