Photo by Larry Young
SAN FRANCISCO—Interim results of a phase 3 trial suggest 2 treatment regimens may provide comparable efficacy in patients with extranodal natural killer/T-cell lymphoma (ENKTL), though 1 regimen appears more toxic than the other.
In this ongoing trial, investigators are comparing pegaspargase, gemcitabine, oxaliplatin, and thalidomide (P-Gemox+Thal) to pegaspargase, methotrexate, calcium folinate, and dexamethasone (AspaMetDex).
In some patients, either regimen may be followed by extensive involved-field radiotherapy (EIFRT) or autologous hematopoietic stem cell transplant (ASCT).
Thus far, P-Gemox+Thal and AspaMetDex have proven similarly effective for patients with newly diagnosed, stage I/II ENKTL.
And both regimens have produced unsatisfying survival outcomes in patients with advanced or relapsed/refractory ENKTL, according to investigator Huiqiang Huang, MD, of Sun Yat-sen Institute of Hematology in Guangzhou, China.
In addition, P-Gemox+Thal seems to be less toxic, overall, than AspaMetDex.
However, Dr Huang said it is still too early to draw any firm conclusions about these regimens.
He presented results from this trial at the 9th Annual T-cell Lymphoma Forum. Results were previously presented at the 2016 ASH Annual Meeting (abstract 1819).
Dr Huang noted that AspaMetDex and SMILE (dexamethasone, methotrexate, ifosfamide, lL-asparaginase, and etoposide) are frequently administered to patients with ENKTL. And P-Gemox is recommended in the 2016 NCCN guidelines.
“But optimal regimens still have not been fully defined,” he said.
Therefore, he and his colleagues decided to compare AspaMetDex to P-Gemox+Thal in this non-inferiority trial, which has enrolled 110 patients from 12 centers in China.
Treatment
Fifty-six patients have been randomized to receive P-Gemox+Thal. Every 3 weeks, they received pegaspargase at 2000 U/m2 on day 1, gemcitabine at 1000 mg/m2 on days 1 and 8, and oxaliplatin at 130 mg/m2 on days 1 and 8. They also received thalidomide at 100 mg every day for 1 year.
Fifty-four patients have been randomized to receive AspaMetDex. Every 3 weeks, they received pegaspargase at 2000 U/m2 on day 1, methotrexate at 3000 mg/m2 on day 1, calcium folinate at 30 mg every 6 hours until a safe serum methotrexate concentration was reached, and dexamethasone at 40 mg every day on days 1 to 4.
Newly diagnosed patients with stage I/II disease received either regimen as induction for a maximum of 4 cycles. Responders went on to receive EIFRT at 56 Gy in 28 fractions over 4 weeks.
Patients with newly diagnosed, stage III/IV ENKTL or relapsed/refractory ENKTL received either chemotherapy regimen for a maximum of 6 cycles. If they achieved a complete response (CR), these patients could proceed to ASCT.
Stage I/II ENKTL
Of the 63 stage I/II patients, 33 were randomized to P-Gemox+Thal, and 30 received AspaMetDex. In both arms, most patients were male (69.7% and 70%, respectively) and younger than 60 (78.8% and 90%, respectively).
Ninety-seven percent of patients in the P-Gemox+Thal arm had an ECOG status of 0-1, as did 100% of patients in the AspaMetDex arm.
The overall response rate (ORR) was 85.2% in the P-Gemox+Thal arm and 81.5% in the AspaMetDex arm. The CR rate was 59.3% in both arms. The rate of stable disease was 3.7% in the P-Gemox+Thal arm and 11.1% in the AspaMetDex arm.
After EIFRT, the ORR increased to 92.6% in the P-Gemox+Thal arm, and the CR rate increased to 88.8%. In the AspaMetDex arm, the ORR increased to 88.8%, and the CR rate increased to 85.1%.
At a median follow-up of 13.5 months, the 2-year progression-free survival rate was 82.9% in the P-Gemox+Thal arm and 84.5% in the AspaMetDex arm (P=0.791).
The 2-year overall survival rates were 95.0% in the P-Gemox+Thal arm and 75.8% in the AspaMetDex arm (P=0.089).
Advanced, rel/ref ENKTL
Of the 47 patients with stage III/IV or relapsed/refractory ENKTL, 24 were randomized to P-Gemox+Thal, and 23 to AspaMetDex. In both arms, most patients were male (75% and 87%, respectively) and younger than 60 (95.8% and 91.3%, respectively).
ECOG status was 0 for 62.5% of patients in the P-Gemox+Thal arm and 73.9% of those in the AspaMetDex arm. ECOG status was 1 for 33.3% and 17.4%, respectively.
The ORR was 86.3% in the P-Gemox+Thal arm and 70% in the AspaMetDex arm. The CR rate was 50% in both arms.
The partial response rate was 36.3% in the P-Gemox+Thal arm and 20% in the AspaMetDex arm. And the rate of stable disease was 13.6% and 15%, respectively.
Three patients in each treatment arm went on to ASCT after CR. A total of 3 patients relapsed within 6 months of ASCT—2 in the P-Gemox+Thal arm and 1 in the AspaMetDex arm. Two patients died of disease progression.
At a median follow-up of 14.5 months, the 2-year progression-free survival was 12.2 months in the P-Gemox+Thal arm and 7.6 months in the AspaMetDex arm (P=0.365).
The 2-year overall survival was 52.5% in the P-Gemox+Thal arm and 48.9% in the AspaMetDex arm (P=0.935).
Overall safety
Rates of leukopenia, thrombocytopenia, and ALT/AST increase were all significantly higher with P-Gemox+Thal than with AspaMetDex—100% vs 66.7% (P<0.001), 64.2% vs 35.2% (P=0.005), and 69.6% vs 64.8% (P=0.004), respectively.
Rates of anemia and edema were significantly higher with AspaMetDex than with P-Gemox+Thal—51.8% vs 77.8% (P=0.005) and 37.5% vs 66.7% (P=0.003), respectively.
There were 3 treatment-related deaths in the AspaMetDex arm but none in the P-Gemox+Thal arm. Two of the treatment-related deaths—from severe acute renal failure and sepsis—occurred in the first cycle, and 1 death—due to severe sepsis—occurred in the third cycle.
The median hospitalization time was significantly shorter in the P-Gemox+Thal arm than the AspaMetDex arm—1.9 days and 4.9 days, respectively (P<0.01).
Based on these results, Dr Huang said P-Gemox+Thal may be more tolerable and provide more convenient administration than AspaMetDex.
