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Adverse events limited the dose intensity or schedule of chemotherapy when added to nivolumab in patients with treatment-naive advanced gastric cancer, according to results from a small, phase 2 trial.
Fully 95% of patients delayed or reduced the dose of chemotherapy because of adverse events. Serious (grade 3 or higher) treatment-related adverse events affected 15% of patients and 13% of patients stopped treatment because of adverse events, said Narikazu Boku, MD, PhD, of National Cancer Center Hospital in Tokyo, together with his associates. The findings were published in Annals of Oncology.
Nivolumab (Opdivo) is not approved for treating gastric cancer in the United States but is approved as third-line or later therapy in several other countries. In the phase 2 ATTRACTION-4 trial, 39 patients with previously untreated, unresectable, advanced, or recurrent gastric or gastroesophageal junction cancer received nivolumab (360 mg intravenously every 3 weeks), plus either S-1 (40 mg/m2 orally twice daily for 14 days followed by 7 days off) or capecitabine (1000 mg/m2 orally twice daily for 14 days followed by 7 days off), plus oxaliplatin (130 mg/m2 intravenously on day 1 every 3 weeks).
For the regimen containing S-1, the most common serious adverse events requiring delays or reductions in chemotherapy were thrombocytopenia (57%), neutropenia (48%), and nausea (19%), followed by diarrhea, vomiting, abdominal pain, peripheral sensory neuropathy, and fatigue (14% each). For the regimen containing capecitabine, the most common of these adverse events were neutropenia (44%), decreased appetite (28%), and palmar-plantar erythrodysesthesia syndrome (22%), followed by nausea, vomiting, diarrhea, and peripheral sensory neuropathy (17% each). There were no treatment-related deaths.
Efficacy endpoints were secondary and limited by small sample size. Nonetheless, regardless of which of the two chemotherapy regimens patients received, about two-thirds had a complete or partial treatment response, which is “numerically higher” than that reported for either chemotherapy regimen alone, the researchers wrote. After a median follow-up of 13.2 months, median overall survival was not reached, while median progression-free survival was 9.7 months for the S-1-based regimen and 10.6 months for the capecitabine-based regimen. Antitumor response appeared to be unrelated to programmed death–ligand 1 status.
Based on the findings, both nivolumab-chemotherapy regimens have “manageable safety profile and clinically relevant antitumor profile,” Dr. Boku and his coinvestigators stated. The second part of ATTRACTION-4 has recruited a larger group of patients and should shed more light on efficacy.
Ono Pharmaceutical and Bristol-Myers Squibb funded the work. Dr. Boku reported financial ties to both companies and to AstraZeneca and Chugai Pharmaceutical.
SOURCE: Boku N et al. Ann Oncol. 2018 Dec 19. doi: 10.1093/annonc/mdy540.
Although ATTRACTION-4 investigators called the safety profile of nivolumab plus chemotherapy in gastric cancer “manageable,” 95% of patients required chemotherapy dose delays or reductions because of treatment-emergent adverse events, noted Elizabeth Cartwright, MBBS, and Ian Chau, MD, in an editorial accompanying the study.
“Given the small safety population in the study, comparisons between arms cannot be made; nonetheless, the overall high rate of treatment-related adverse events across arms could impact patient care and standard chemotherapy dose intensity,” they wrote.
The small cohort sizes also limit conclusions regarding efficacy, they added. Although the data seem encouraging, the efficacy population of 38 patients “is more reflective of a safety run-in rather than a true randomized, phase 2 design, and the results are too preliminary to draw comparisons or conclusions against first-line standard-of-care chemotherapy.”
Finally, the study lacked quality-of-life data and was conducted exclusively in Japan and Korea. Gastric cancers from Asian and non-Asian patients show differences in the expression of genes related to immune function, which could affect treatment response, the experts wrote. Hence, they await results not only from the larger second part of ATTRACTION-4, but also from CheckMate 649, which “will provide a large, randomized, global parallel.”
Both editorialists are with Royal Marsden Hospital in London. Dr. Cartwright reported having no conflicts of interest. Dr. Chau reported ties to Bristol-Myers Squibb, which markets nivolumab in the United States, and to several other pharmaceutical companies. These comments are from their editorial (Ann Oncol. 2018 Dec 28. doi: 10.1093/annonc/mdy555).
Although ATTRACTION-4 investigators called the safety profile of nivolumab plus chemotherapy in gastric cancer “manageable,” 95% of patients required chemotherapy dose delays or reductions because of treatment-emergent adverse events, noted Elizabeth Cartwright, MBBS, and Ian Chau, MD, in an editorial accompanying the study.
“Given the small safety population in the study, comparisons between arms cannot be made; nonetheless, the overall high rate of treatment-related adverse events across arms could impact patient care and standard chemotherapy dose intensity,” they wrote.
The small cohort sizes also limit conclusions regarding efficacy, they added. Although the data seem encouraging, the efficacy population of 38 patients “is more reflective of a safety run-in rather than a true randomized, phase 2 design, and the results are too preliminary to draw comparisons or conclusions against first-line standard-of-care chemotherapy.”
Finally, the study lacked quality-of-life data and was conducted exclusively in Japan and Korea. Gastric cancers from Asian and non-Asian patients show differences in the expression of genes related to immune function, which could affect treatment response, the experts wrote. Hence, they await results not only from the larger second part of ATTRACTION-4, but also from CheckMate 649, which “will provide a large, randomized, global parallel.”
Both editorialists are with Royal Marsden Hospital in London. Dr. Cartwright reported having no conflicts of interest. Dr. Chau reported ties to Bristol-Myers Squibb, which markets nivolumab in the United States, and to several other pharmaceutical companies. These comments are from their editorial (Ann Oncol. 2018 Dec 28. doi: 10.1093/annonc/mdy555).
Although ATTRACTION-4 investigators called the safety profile of nivolumab plus chemotherapy in gastric cancer “manageable,” 95% of patients required chemotherapy dose delays or reductions because of treatment-emergent adverse events, noted Elizabeth Cartwright, MBBS, and Ian Chau, MD, in an editorial accompanying the study.
“Given the small safety population in the study, comparisons between arms cannot be made; nonetheless, the overall high rate of treatment-related adverse events across arms could impact patient care and standard chemotherapy dose intensity,” they wrote.
The small cohort sizes also limit conclusions regarding efficacy, they added. Although the data seem encouraging, the efficacy population of 38 patients “is more reflective of a safety run-in rather than a true randomized, phase 2 design, and the results are too preliminary to draw comparisons or conclusions against first-line standard-of-care chemotherapy.”
Finally, the study lacked quality-of-life data and was conducted exclusively in Japan and Korea. Gastric cancers from Asian and non-Asian patients show differences in the expression of genes related to immune function, which could affect treatment response, the experts wrote. Hence, they await results not only from the larger second part of ATTRACTION-4, but also from CheckMate 649, which “will provide a large, randomized, global parallel.”
Both editorialists are with Royal Marsden Hospital in London. Dr. Cartwright reported having no conflicts of interest. Dr. Chau reported ties to Bristol-Myers Squibb, which markets nivolumab in the United States, and to several other pharmaceutical companies. These comments are from their editorial (Ann Oncol. 2018 Dec 28. doi: 10.1093/annonc/mdy555).
Adverse events limited the dose intensity or schedule of chemotherapy when added to nivolumab in patients with treatment-naive advanced gastric cancer, according to results from a small, phase 2 trial.
Fully 95% of patients delayed or reduced the dose of chemotherapy because of adverse events. Serious (grade 3 or higher) treatment-related adverse events affected 15% of patients and 13% of patients stopped treatment because of adverse events, said Narikazu Boku, MD, PhD, of National Cancer Center Hospital in Tokyo, together with his associates. The findings were published in Annals of Oncology.
Nivolumab (Opdivo) is not approved for treating gastric cancer in the United States but is approved as third-line or later therapy in several other countries. In the phase 2 ATTRACTION-4 trial, 39 patients with previously untreated, unresectable, advanced, or recurrent gastric or gastroesophageal junction cancer received nivolumab (360 mg intravenously every 3 weeks), plus either S-1 (40 mg/m2 orally twice daily for 14 days followed by 7 days off) or capecitabine (1000 mg/m2 orally twice daily for 14 days followed by 7 days off), plus oxaliplatin (130 mg/m2 intravenously on day 1 every 3 weeks).
For the regimen containing S-1, the most common serious adverse events requiring delays or reductions in chemotherapy were thrombocytopenia (57%), neutropenia (48%), and nausea (19%), followed by diarrhea, vomiting, abdominal pain, peripheral sensory neuropathy, and fatigue (14% each). For the regimen containing capecitabine, the most common of these adverse events were neutropenia (44%), decreased appetite (28%), and palmar-plantar erythrodysesthesia syndrome (22%), followed by nausea, vomiting, diarrhea, and peripheral sensory neuropathy (17% each). There were no treatment-related deaths.
Efficacy endpoints were secondary and limited by small sample size. Nonetheless, regardless of which of the two chemotherapy regimens patients received, about two-thirds had a complete or partial treatment response, which is “numerically higher” than that reported for either chemotherapy regimen alone, the researchers wrote. After a median follow-up of 13.2 months, median overall survival was not reached, while median progression-free survival was 9.7 months for the S-1-based regimen and 10.6 months for the capecitabine-based regimen. Antitumor response appeared to be unrelated to programmed death–ligand 1 status.
Based on the findings, both nivolumab-chemotherapy regimens have “manageable safety profile and clinically relevant antitumor profile,” Dr. Boku and his coinvestigators stated. The second part of ATTRACTION-4 has recruited a larger group of patients and should shed more light on efficacy.
Ono Pharmaceutical and Bristol-Myers Squibb funded the work. Dr. Boku reported financial ties to both companies and to AstraZeneca and Chugai Pharmaceutical.
SOURCE: Boku N et al. Ann Oncol. 2018 Dec 19. doi: 10.1093/annonc/mdy540.
Adverse events limited the dose intensity or schedule of chemotherapy when added to nivolumab in patients with treatment-naive advanced gastric cancer, according to results from a small, phase 2 trial.
Fully 95% of patients delayed or reduced the dose of chemotherapy because of adverse events. Serious (grade 3 or higher) treatment-related adverse events affected 15% of patients and 13% of patients stopped treatment because of adverse events, said Narikazu Boku, MD, PhD, of National Cancer Center Hospital in Tokyo, together with his associates. The findings were published in Annals of Oncology.
Nivolumab (Opdivo) is not approved for treating gastric cancer in the United States but is approved as third-line or later therapy in several other countries. In the phase 2 ATTRACTION-4 trial, 39 patients with previously untreated, unresectable, advanced, or recurrent gastric or gastroesophageal junction cancer received nivolumab (360 mg intravenously every 3 weeks), plus either S-1 (40 mg/m2 orally twice daily for 14 days followed by 7 days off) or capecitabine (1000 mg/m2 orally twice daily for 14 days followed by 7 days off), plus oxaliplatin (130 mg/m2 intravenously on day 1 every 3 weeks).
For the regimen containing S-1, the most common serious adverse events requiring delays or reductions in chemotherapy were thrombocytopenia (57%), neutropenia (48%), and nausea (19%), followed by diarrhea, vomiting, abdominal pain, peripheral sensory neuropathy, and fatigue (14% each). For the regimen containing capecitabine, the most common of these adverse events were neutropenia (44%), decreased appetite (28%), and palmar-plantar erythrodysesthesia syndrome (22%), followed by nausea, vomiting, diarrhea, and peripheral sensory neuropathy (17% each). There were no treatment-related deaths.
Efficacy endpoints were secondary and limited by small sample size. Nonetheless, regardless of which of the two chemotherapy regimens patients received, about two-thirds had a complete or partial treatment response, which is “numerically higher” than that reported for either chemotherapy regimen alone, the researchers wrote. After a median follow-up of 13.2 months, median overall survival was not reached, while median progression-free survival was 9.7 months for the S-1-based regimen and 10.6 months for the capecitabine-based regimen. Antitumor response appeared to be unrelated to programmed death–ligand 1 status.
Based on the findings, both nivolumab-chemotherapy regimens have “manageable safety profile and clinically relevant antitumor profile,” Dr. Boku and his coinvestigators stated. The second part of ATTRACTION-4 has recruited a larger group of patients and should shed more light on efficacy.
Ono Pharmaceutical and Bristol-Myers Squibb funded the work. Dr. Boku reported financial ties to both companies and to AstraZeneca and Chugai Pharmaceutical.
SOURCE: Boku N et al. Ann Oncol. 2018 Dec 19. doi: 10.1093/annonc/mdy540.
FROM ANNALS OF ONCOLOGY
Key clinical point: Adverse events limited the dose intensity of chemotherapy when added to nivolumab in patients with treatment-naive advanced gastric cancer.
Major finding: Almost all (95%) patients required dose delays or reductions because of adverse events. Serious adverse events affected 15% of patients and in most cases led to treatment discontinuation.
Study details: A phase 2 trial of nivolumab, plus either S-1 or capecitabine, plus oxaliplatin in 39 patients with previously untreated, unresectable, advanced, or recurrent gastric or gastroesophageal junction cancer.
Disclosures: Ono Pharmaceutical and Bristol-Myers Squibb funded the work. Dr. Boku reported financial ties to both companies and to AstraZeneca and Chugai Pharmaceutical.
Source: Boku N et al. Ann Oncol. 2018 Dec 19. doi: 10.1093/annonc/mdy540.