Iniparib Adds No Survival Benefit in Lung Cancer Trial

STOCKHOLM – Adding the investigational drug iniparib to a gemcitabine and cisplatin doublet failed to improve outcomes significantly in a phase II study of 119 patients with advanced non–small-cell lung cancer.

The disappointing result follows a phase III trial in which iniparib failed to confirm survival gains when added to gemcitabine (Gemzar) and carboplatin chemotherapy in patients with metastatic triple-negative breast cancer.

Iniparib (BSI-201) had been the leading agent in a new class of therapeutics known as PARP (poly [ADP (adenosine diphosphate)–ribose] polymerase) inhibitors, but the phase III flop in breast cancer left researchers questioning whether it has a different mechanism of action.

In the current lung cancer trial, median progression-free survival was slightly longer at 5.7 months in those who received iniparib in addition to gemcitabine/cisplatinchemotherapy, compared with 4.3 months for those on gemcitabine/cisplatin alone. The difference was not statistically significant, however (hazard ratio, 0.89; P = .48).

Based on preliminary data at a median follow-up of 8.4 months, median overall survival was 8.5 months for the doublet-only arm and 11.2 months for the iniparib arm, Dr. Silvia Novello reported at the European Multidisciplinary Cancer Congress. Both survival measures were secondary end points.

"Be cautious when interpreting the 1.4-month increase in median progression-free survival and when interpreting the preliminary 2.7 months in median OS [overall survival] seen in the investigational arm vs. the chemotherapy arm because this could be due to differences in baseline patient characteristics," Dr. Novello told attendees at the joint congress of the European Cancer Organization, the European Society for Medical Oncology, and the European Society for Radiotherapy and Oncology.

In particular, ECOG (Eastern Cooperative Oncology Group) performance status and sex were not balanced, with more patients having a performance status of 0 (61% vs. 49%) and more men (80% vs. 67%) in the investigational arm than in the control group, explained Dr. Novello, a thoracic oncologist at the University of Torino (Italy).

The study’s primary end point was overall response rate as determined by investigators using RECIST 1.1. The investigators previously reported this measure of complete and partial responses was higher in the control group – 26% for those on gemcitabine/cisplatin alone and 20% for those in the doublet plus iniparib group. The only complete response was in a patient given iniparib.

The study included patients who had measurable, untreated stage IV non–small-cell lung cancer (NSCLC) and an ECOG performance status of 0-1. They were randomized 2:1 to receive gemcitabine/cisplatin plus iniparib (80 patients) or gemcitabine/cisplatin alone (39 patients).

Roughly half of patients in each group completed five to six cycles – 44% vs. 50% for the chemotherapy and investigational arms.

Gemcitabine 1,250 mg/m² was given intravenously on days 1 and 8, and cisplatin was given 75 mg/m² intravenously on day 1 in 21-day cycles. Iniparib 5.6 mg/kg also was given intravenously on days 1, 4, 8, and 11 in the experimental arm. Patients underwent a maximum of six cycles, with no maintenance phase.

Safety data showed 82% of the chemotherapy arm and 85% of the iniparib arm had any grade 3/4 treatment-emergent adverse events.

Anemia and nausea were more common in the iniparib arm, but other common adverse events were essentially the same.

Biomarker studies are ongoing potentially to define a subgroup of patients who may benefit from iniparib treatment, according to Dr. Novello.

Invited discussant Dr. Luis Paz-Ares, medial oncology chief of service at Hospital Universitario Virgen del Rocio in Seville, Spain, emphasized the importance of this substudy. "I think it would be very relevant to know if there are some subsets of patients that may benefit," he said. "I think the main part of this trial is the markers, and I will be very interested to see the results of this."

The study is sponsored by Sanofi-Aventis in collaboration with BiPar Sciences. Dr. Novello has previously reported that she has no relevant financial disclosures.

STOCKHOLM – Adding the investigational drug iniparib to a gemcitabine and cisplatin doublet failed to improve outcomes significantly in a phase II study of 119 patients with advanced non–small-cell lung cancer.

The disappointing result follows a phase III trial in which iniparib failed to confirm survival gains when added to gemcitabine (Gemzar) and carboplatin chemotherapy in patients with metastatic triple-negative breast cancer.

Iniparib (BSI-201) had been the leading agent in a new class of therapeutics known as PARP (poly [ADP (adenosine diphosphate)–ribose] polymerase) inhibitors, but the phase III flop in breast cancer left researchers questioning whether it has a different mechanism of action.

In the current lung cancer trial, median progression-free survival was slightly longer at 5.7 months in those who received iniparib in addition to gemcitabine/cisplatinchemotherapy, compared with 4.3 months for those on gemcitabine/cisplatin alone. The difference was not statistically significant, however (hazard ratio, 0.89; P = .48).

Based on preliminary data at a median follow-up of 8.4 months, median overall survival was 8.5 months for the doublet-only arm and 11.2 months for the iniparib arm, Dr. Silvia Novello reported at the European Multidisciplinary Cancer Congress. Both survival measures were secondary end points.

"Be cautious when interpreting the 1.4-month increase in median progression-free survival and when interpreting the preliminary 2.7 months in median OS [overall survival] seen in the investigational arm vs. the chemotherapy arm because this could be due to differences in baseline patient characteristics," Dr. Novello told attendees at the joint congress of the European Cancer Organization, the European Society for Medical Oncology, and the European Society for Radiotherapy and Oncology.

In particular, ECOG (Eastern Cooperative Oncology Group) performance status and sex were not balanced, with more patients having a performance status of 0 (61% vs. 49%) and more men (80% vs. 67%) in the investigational arm than in the control group, explained Dr. Novello, a thoracic oncologist at the University of Torino (Italy).

The study’s primary end point was overall response rate as determined by investigators using RECIST 1.1. The investigators previously reported this measure of complete and partial responses was higher in the control group – 26% for those on gemcitabine/cisplatin alone and 20% for those in the doublet plus iniparib group. The only complete response was in a patient given iniparib.

The study included patients who had measurable, untreated stage IV non–small-cell lung cancer (NSCLC) and an ECOG performance status of 0-1. They were randomized 2:1 to receive gemcitabine/cisplatin plus iniparib (80 patients) or gemcitabine/cisplatin alone (39 patients).

Roughly half of patients in each group completed five to six cycles – 44% vs. 50% for the chemotherapy and investigational arms.

Gemcitabine 1,250 mg/m² was given intravenously on days 1 and 8, and cisplatin was given 75 mg/m² intravenously on day 1 in 21-day cycles. Iniparib 5.6 mg/kg also was given intravenously on days 1, 4, 8, and 11 in the experimental arm. Patients underwent a maximum of six cycles, with no maintenance phase.

Safety data showed 82% of the chemotherapy arm and 85% of the iniparib arm had any grade 3/4 treatment-emergent adverse events.

Anemia and nausea were more common in the iniparib arm, but other common adverse events were essentially the same.

Biomarker studies are ongoing potentially to define a subgroup of patients who may benefit from iniparib treatment, according to Dr. Novello.

Invited discussant Dr. Luis Paz-Ares, medial oncology chief of service at Hospital Universitario Virgen del Rocio in Seville, Spain, emphasized the importance of this substudy. "I think it would be very relevant to know if there are some subsets of patients that may benefit," he said. "I think the main part of this trial is the markers, and I will be very interested to see the results of this."

The study is sponsored by Sanofi-Aventis in collaboration with BiPar Sciences. Dr. Novello has previously reported that she has no relevant financial disclosures.

STOCKHOLM – Adding the investigational drug iniparib to a gemcitabine and cisplatin doublet failed to improve outcomes significantly in a phase II study of 119 patients with advanced non–small-cell lung cancer.

The disappointing result follows a phase III trial in which iniparib failed to confirm survival gains when added to gemcitabine (Gemzar) and carboplatin chemotherapy in patients with metastatic triple-negative breast cancer.

Iniparib (BSI-201) had been the leading agent in a new class of therapeutics known as PARP (poly [ADP (adenosine diphosphate)–ribose] polymerase) inhibitors, but the phase III flop in breast cancer left researchers questioning whether it has a different mechanism of action.

In the current lung cancer trial, median progression-free survival was slightly longer at 5.7 months in those who received iniparib in addition to gemcitabine/cisplatinchemotherapy, compared with 4.3 months for those on gemcitabine/cisplatin alone. The difference was not statistically significant, however (hazard ratio, 0.89; P = .48).

Based on preliminary data at a median follow-up of 8.4 months, median overall survival was 8.5 months for the doublet-only arm and 11.2 months for the iniparib arm, Dr. Silvia Novello reported at the European Multidisciplinary Cancer Congress. Both survival measures were secondary end points.

"Be cautious when interpreting the 1.4-month increase in median progression-free survival and when interpreting the preliminary 2.7 months in median OS [overall survival] seen in the investigational arm vs. the chemotherapy arm because this could be due to differences in baseline patient characteristics," Dr. Novello told attendees at the joint congress of the European Cancer Organization, the European Society for Medical Oncology, and the European Society for Radiotherapy and Oncology.

In particular, ECOG (Eastern Cooperative Oncology Group) performance status and sex were not balanced, with more patients having a performance status of 0 (61% vs. 49%) and more men (80% vs. 67%) in the investigational arm than in the control group, explained Dr. Novello, a thoracic oncologist at the University of Torino (Italy).

The study’s primary end point was overall response rate as determined by investigators using RECIST 1.1. The investigators previously reported this measure of complete and partial responses was higher in the control group – 26% for those on gemcitabine/cisplatin alone and 20% for those in the doublet plus iniparib group. The only complete response was in a patient given iniparib.

The study included patients who had measurable, untreated stage IV non–small-cell lung cancer (NSCLC) and an ECOG performance status of 0-1. They were randomized 2:1 to receive gemcitabine/cisplatin plus iniparib (80 patients) or gemcitabine/cisplatin alone (39 patients).

Roughly half of patients in each group completed five to six cycles – 44% vs. 50% for the chemotherapy and investigational arms.

Gemcitabine 1,250 mg/m² was given intravenously on days 1 and 8, and cisplatin was given 75 mg/m² intravenously on day 1 in 21-day cycles. Iniparib 5.6 mg/kg also was given intravenously on days 1, 4, 8, and 11 in the experimental arm. Patients underwent a maximum of six cycles, with no maintenance phase.

Safety data showed 82% of the chemotherapy arm and 85% of the iniparib arm had any grade 3/4 treatment-emergent adverse events.

Anemia and nausea were more common in the iniparib arm, but other common adverse events were essentially the same.

Biomarker studies are ongoing potentially to define a subgroup of patients who may benefit from iniparib treatment, according to Dr. Novello.

Invited discussant Dr. Luis Paz-Ares, medial oncology chief of service at Hospital Universitario Virgen del Rocio in Seville, Spain, emphasized the importance of this substudy. "I think it would be very relevant to know if there are some subsets of patients that may benefit," he said. "I think the main part of this trial is the markers, and I will be very interested to see the results of this."

The study is sponsored by Sanofi-Aventis in collaboration with BiPar Sciences. Dr. Novello has previously reported that she has no relevant financial disclosures.