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In chemotherapy-naive patients with metastatic melanoma, progression-free survival (PFS) was significantly longer with nab-paclitaxel, compared with dacarbazine, according to results from a phase III trial.
Median PFS for the nab-paclitaxel arm vs. the dacarbazine arm was 4.8 vs. 2.5 months, respectively (hazard ratio, 0.792; 95% confidence interval, 0.631-0.992; P = .044). Overall survival was similar in the two arms: 12.6 months for nab-paclitaxel vs. 10.5 months for dacarbazine (P = .27). The nab-paclitaxel group had an increased, but not significant, overall response rate (15% vs. 11%) and a significantly improved disease control rate (P = .004). The disease control rate reflects the number of complete responses plus partial responses plus stable disease for 16 or more weeks.
Nab-paclitaxel benefited patients regardless of BRAF mutation status, noted Dr. Evan Hersh, professor of medicine at the University of Arizona, Tucson, and colleagues.
“Additionally, in a post hoc analysis of this trial, nab-paclitaxel was shown to benefit a subgroup of patients with low or absent TILs [tumor-infiltrating lymphocytes], a poor prognostic factor in melanoma,” they wrote (Ann Oncol 2015 Sep 26. doi: 10.1093/annonc/mdv324).
The most common treatment-related adverse events of grade 3 or greater were neuropathy (25% vs. 0%), neutropenia (20% vs. 10%), and leukopenia (12% vs. 7%) for the nab-paclitaxel and dacarbazine arms, respectively. The median onset of grade 3 or greater peripheral neuropathy was 101 days after treatment began.
Between April 2009 and June 2011, the multicenter, phase III, randomized, controlled trial enrolled 529 adults with stage IV malignant melanoma who had no prior cytotoxic therapy.
A majority of participants from both treatment arms underwent post-study therapy, including newer agents such as BRAF inhibitors and ipilimumab. This may account for the diminished treatment affect of nab-paclitaxel on overall survival, compared with the more significant benefit in PFS observed early in the study.
A biomarker analysis found no correlation between tumor expression of the albumin-binding protein SPARC and PFS with nab-paclitaxel treatment. SPARC was hypothesized to enrich nab-paclitaxel in the tumor microenvironment thereby increasing its efficacy.
The study by Hersh et al. was conceived prior to the success of immune checkpoint inhibitors and targeted therapies for melanoma. The treatment landscape has changed rapidly, and the current role of chemotherapy, and nab-paclitaxel specifically, is uncertain.
In the last 5 years, four classes of therapies have significantly improved overall survival over dacarbazine: ipilimumab (HR, 0.72; P less than .001), vemurafenib (HR, 0.37; P less than .001), trametinib (HR, 0.54; P = .01), and nivolumab (HR, 0.42; P less than .001).
For the large majority of patients, chemotherapy would not be considered for the first line of therapy. Patients typically considered for chemotherapy would have failed or would have been intolerant to ipilimumab and an anti-PD1 agent, as well as BRAF/MEK inhibitors if the tumors were BRAF-mutation positive. In these heavily pretreated patients, however, toxicities associated with chemotherapy may outweigh benefits.
In patients with a history of autoimmune disease, some have suggested checkpoint inhibitors may exacerbate these conditions. However, recent retrospective studies suggest that ipilimumab is safe for patients with autoimmune disorders such as inflammatory bowel disease and rheumatoid arthritis.
The current study did not include quality of life data, and given the lack of improvement in overall survival, the superiority of nab-paclitaxel over dacarbazine has not been shown definitively.
Chemotherapy may have a role in combination with targeted or immunotherapeutic agents. Checkpoint inhibitors may be more active in patients with baseline tumor-infiltrating lymphocytes (TILs) and tumor PDL1 expression. Chemotherapy may induce TILs in tumors where the cells are low or absent, and nab-paclitaxel may be a good candidate to explore such combinations.
It remains to be determined if chemotherapy offers greater benefit than the many other strategies under consideration. This brings to the forefront the urgent need for preclinical models to enable comparisons of combination strategies.
Dr. Matteo Carlino is a clinical senior lecturer at the Sydney Medical School, University of Sydney and a medical oncologist at Westmead Hospital and Blacktown Hospital, Australia. Dr. Georgina Long is an associate professor and medical oncologist at Melanoma Institute Australia, University of Sydney. These remarks were part of an editorial accompanying the report (Ann Oncol. 2015 Sep 15. doi: 10.1093/annonc/mdv361). Dr. Carlino and Dr. Long reported having no disclosures.
The study by Hersh et al. was conceived prior to the success of immune checkpoint inhibitors and targeted therapies for melanoma. The treatment landscape has changed rapidly, and the current role of chemotherapy, and nab-paclitaxel specifically, is uncertain.
In the last 5 years, four classes of therapies have significantly improved overall survival over dacarbazine: ipilimumab (HR, 0.72; P less than .001), vemurafenib (HR, 0.37; P less than .001), trametinib (HR, 0.54; P = .01), and nivolumab (HR, 0.42; P less than .001).
For the large majority of patients, chemotherapy would not be considered for the first line of therapy. Patients typically considered for chemotherapy would have failed or would have been intolerant to ipilimumab and an anti-PD1 agent, as well as BRAF/MEK inhibitors if the tumors were BRAF-mutation positive. In these heavily pretreated patients, however, toxicities associated with chemotherapy may outweigh benefits.
In patients with a history of autoimmune disease, some have suggested checkpoint inhibitors may exacerbate these conditions. However, recent retrospective studies suggest that ipilimumab is safe for patients with autoimmune disorders such as inflammatory bowel disease and rheumatoid arthritis.
The current study did not include quality of life data, and given the lack of improvement in overall survival, the superiority of nab-paclitaxel over dacarbazine has not been shown definitively.
Chemotherapy may have a role in combination with targeted or immunotherapeutic agents. Checkpoint inhibitors may be more active in patients with baseline tumor-infiltrating lymphocytes (TILs) and tumor PDL1 expression. Chemotherapy may induce TILs in tumors where the cells are low or absent, and nab-paclitaxel may be a good candidate to explore such combinations.
It remains to be determined if chemotherapy offers greater benefit than the many other strategies under consideration. This brings to the forefront the urgent need for preclinical models to enable comparisons of combination strategies.
Dr. Matteo Carlino is a clinical senior lecturer at the Sydney Medical School, University of Sydney and a medical oncologist at Westmead Hospital and Blacktown Hospital, Australia. Dr. Georgina Long is an associate professor and medical oncologist at Melanoma Institute Australia, University of Sydney. These remarks were part of an editorial accompanying the report (Ann Oncol. 2015 Sep 15. doi: 10.1093/annonc/mdv361). Dr. Carlino and Dr. Long reported having no disclosures.
The study by Hersh et al. was conceived prior to the success of immune checkpoint inhibitors and targeted therapies for melanoma. The treatment landscape has changed rapidly, and the current role of chemotherapy, and nab-paclitaxel specifically, is uncertain.
In the last 5 years, four classes of therapies have significantly improved overall survival over dacarbazine: ipilimumab (HR, 0.72; P less than .001), vemurafenib (HR, 0.37; P less than .001), trametinib (HR, 0.54; P = .01), and nivolumab (HR, 0.42; P less than .001).
For the large majority of patients, chemotherapy would not be considered for the first line of therapy. Patients typically considered for chemotherapy would have failed or would have been intolerant to ipilimumab and an anti-PD1 agent, as well as BRAF/MEK inhibitors if the tumors were BRAF-mutation positive. In these heavily pretreated patients, however, toxicities associated with chemotherapy may outweigh benefits.
In patients with a history of autoimmune disease, some have suggested checkpoint inhibitors may exacerbate these conditions. However, recent retrospective studies suggest that ipilimumab is safe for patients with autoimmune disorders such as inflammatory bowel disease and rheumatoid arthritis.
The current study did not include quality of life data, and given the lack of improvement in overall survival, the superiority of nab-paclitaxel over dacarbazine has not been shown definitively.
Chemotherapy may have a role in combination with targeted or immunotherapeutic agents. Checkpoint inhibitors may be more active in patients with baseline tumor-infiltrating lymphocytes (TILs) and tumor PDL1 expression. Chemotherapy may induce TILs in tumors where the cells are low or absent, and nab-paclitaxel may be a good candidate to explore such combinations.
It remains to be determined if chemotherapy offers greater benefit than the many other strategies under consideration. This brings to the forefront the urgent need for preclinical models to enable comparisons of combination strategies.
Dr. Matteo Carlino is a clinical senior lecturer at the Sydney Medical School, University of Sydney and a medical oncologist at Westmead Hospital and Blacktown Hospital, Australia. Dr. Georgina Long is an associate professor and medical oncologist at Melanoma Institute Australia, University of Sydney. These remarks were part of an editorial accompanying the report (Ann Oncol. 2015 Sep 15. doi: 10.1093/annonc/mdv361). Dr. Carlino and Dr. Long reported having no disclosures.
In chemotherapy-naive patients with metastatic melanoma, progression-free survival (PFS) was significantly longer with nab-paclitaxel, compared with dacarbazine, according to results from a phase III trial.
Median PFS for the nab-paclitaxel arm vs. the dacarbazine arm was 4.8 vs. 2.5 months, respectively (hazard ratio, 0.792; 95% confidence interval, 0.631-0.992; P = .044). Overall survival was similar in the two arms: 12.6 months for nab-paclitaxel vs. 10.5 months for dacarbazine (P = .27). The nab-paclitaxel group had an increased, but not significant, overall response rate (15% vs. 11%) and a significantly improved disease control rate (P = .004). The disease control rate reflects the number of complete responses plus partial responses plus stable disease for 16 or more weeks.
Nab-paclitaxel benefited patients regardless of BRAF mutation status, noted Dr. Evan Hersh, professor of medicine at the University of Arizona, Tucson, and colleagues.
“Additionally, in a post hoc analysis of this trial, nab-paclitaxel was shown to benefit a subgroup of patients with low or absent TILs [tumor-infiltrating lymphocytes], a poor prognostic factor in melanoma,” they wrote (Ann Oncol 2015 Sep 26. doi: 10.1093/annonc/mdv324).
The most common treatment-related adverse events of grade 3 or greater were neuropathy (25% vs. 0%), neutropenia (20% vs. 10%), and leukopenia (12% vs. 7%) for the nab-paclitaxel and dacarbazine arms, respectively. The median onset of grade 3 or greater peripheral neuropathy was 101 days after treatment began.
Between April 2009 and June 2011, the multicenter, phase III, randomized, controlled trial enrolled 529 adults with stage IV malignant melanoma who had no prior cytotoxic therapy.
A majority of participants from both treatment arms underwent post-study therapy, including newer agents such as BRAF inhibitors and ipilimumab. This may account for the diminished treatment affect of nab-paclitaxel on overall survival, compared with the more significant benefit in PFS observed early in the study.
A biomarker analysis found no correlation between tumor expression of the albumin-binding protein SPARC and PFS with nab-paclitaxel treatment. SPARC was hypothesized to enrich nab-paclitaxel in the tumor microenvironment thereby increasing its efficacy.
In chemotherapy-naive patients with metastatic melanoma, progression-free survival (PFS) was significantly longer with nab-paclitaxel, compared with dacarbazine, according to results from a phase III trial.
Median PFS for the nab-paclitaxel arm vs. the dacarbazine arm was 4.8 vs. 2.5 months, respectively (hazard ratio, 0.792; 95% confidence interval, 0.631-0.992; P = .044). Overall survival was similar in the two arms: 12.6 months for nab-paclitaxel vs. 10.5 months for dacarbazine (P = .27). The nab-paclitaxel group had an increased, but not significant, overall response rate (15% vs. 11%) and a significantly improved disease control rate (P = .004). The disease control rate reflects the number of complete responses plus partial responses plus stable disease for 16 or more weeks.
Nab-paclitaxel benefited patients regardless of BRAF mutation status, noted Dr. Evan Hersh, professor of medicine at the University of Arizona, Tucson, and colleagues.
“Additionally, in a post hoc analysis of this trial, nab-paclitaxel was shown to benefit a subgroup of patients with low or absent TILs [tumor-infiltrating lymphocytes], a poor prognostic factor in melanoma,” they wrote (Ann Oncol 2015 Sep 26. doi: 10.1093/annonc/mdv324).
The most common treatment-related adverse events of grade 3 or greater were neuropathy (25% vs. 0%), neutropenia (20% vs. 10%), and leukopenia (12% vs. 7%) for the nab-paclitaxel and dacarbazine arms, respectively. The median onset of grade 3 or greater peripheral neuropathy was 101 days after treatment began.
Between April 2009 and June 2011, the multicenter, phase III, randomized, controlled trial enrolled 529 adults with stage IV malignant melanoma who had no prior cytotoxic therapy.
A majority of participants from both treatment arms underwent post-study therapy, including newer agents such as BRAF inhibitors and ipilimumab. This may account for the diminished treatment affect of nab-paclitaxel on overall survival, compared with the more significant benefit in PFS observed early in the study.
A biomarker analysis found no correlation between tumor expression of the albumin-binding protein SPARC and PFS with nab-paclitaxel treatment. SPARC was hypothesized to enrich nab-paclitaxel in the tumor microenvironment thereby increasing its efficacy.
FROM ANNALS OF ONCOLOGY
Key clinical point: Nab-pacilitaxel had significantly longer PFS than dacarbazine in chemotherapy-naive patients with metastatic melanoma.
Major finding: Median PFS in the nab-paclitaxel vs. dacarbazine arms was 4.8 vs. 2.5 months, respectively (HR, 0.792; 95% CI, 0.631-0.992; P = .044).
Data source: The phase III, randomized, controlled trial enrolled 529 patients between April 2009 and June 2011.
Disclosures: Dr. Hersh reported research funding from Celgene. His coauthors reported financial ties to several industry sources.
