Nanoparticle Albumin-bound Paclitaxel Plus Carboplatin Induction Followed by Nanoparticle Albumin-bound Paclitaxel Maintenance in Squamous Non–Small-cell Lung Cancer (ABOUND.sqm): A Phase III Randomized Clinical Trial

BackgroundWe evaluated maintenance nanoparticle albumin-bound (nab) paclitaxel in the treatment of advanced squamous non–small-cell lung cancer.Patients and MethodsPatients with treatment-naive squamous non–small-cell lung cancer received four 21-day cycles of nab-paclitaxel 100 mg/m² on days 1, 8, 15 plus carboplatin area under the curve 6 on day 1 as induction therapy. Patients without disease progression after induction were randomized 2:1 to maintenance nab-paclitaxel 100 mg/m² (days 1 and 8 every 21 days) plus best supportive care (BSC) or BSC alone. The primary endpoint was progression-free survival (PFS). Secondary endpoints included safety and overall survival (OS).ResultsOverall, 420 patients had received induction therapy; 202 (nab-paclitaxel plus BSC, 136; BSC, 66) had received maintenance therapy. Enrollment was discontinued after a preplanned interim futility analysis (patients could remain in the study at the investigator’s discretion). The median PFS was 3.12 months for nab-paclitaxel plus BSC and 2.60 months for BSC; the difference was not statistically significant (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.61-1.19; P = .36). The median OS (median follow-up, 24.2 months) was 17.18 months for nab-paclitaxel plus BSC and 12.16 months for BSC (HR, 0.70; 95% CI, 0.48-1.02; nominal P = .07). An updated analysis (median follow-up, 28.4 months) revealed a median OS of 17.61 months for nab-paclitaxel plus BSC and 12.16 months for BSC (HR, 0.68; 95% CI, 0.47-0.98; nominal P = .037). The most frequent grade 3 and 4 treatment-emergent adverse events for the entire study were neutropenia (53.1% [nab-paclitaxel plus BSC] vs. 50.0% [BSC]) and anemia (33.1% [nab-paclitaxel plus BSC] vs. 32.3% [BSC]). Only peripheral neuropathy had occurred in ≥ 5% of patients during maintenance therapy (13.1%; nab-paclitaxel plus BSC).ConclusionsThe results of the ABOUND.sqm did not meet the primary endpoint of PFS. An updated OS analysis revealed a trend favoring nab-paclitaxel plus BSC.     

Nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma after Folfirinox failure: an AGEO prospective multicentre cohort

Background:

There is currently no standard second-line treatment for metastatic pancreatic adenocarcinoma (MPA), and progression-free survival is consistently <4 months in this setting. The aim of this study was to evaluate the efficacy and tolerability of Nab-paclitaxel plus gemcitabine (A+G) after Folfirinox failure in MPA.

Methods:

From February 2013 to July 2014, all consecutive patients treated with A+G for histologically proven MPA after Folfirinox failure were prospectively enrolled in 12 French centres. A+G was delivered as described in the MPACT trial, until disease progression, patient refusal or unacceptable toxicity.

Results:

Fifty-seven patients were treated with Nab-paclitaxel plus gemcitabine, for a median of 4 cycles (range 1–12). The disease control rate was 58%, with a 17.5% objective response rate. Median overall survival (OS) was 8.8 months (95% CI: 6.2–9.7) and median progression-free survival was 5.1 months (95% CI: 3.2–6.2). Since the start of first-line chemotherapy, median OS was 18 months (95% CI: 16–21). No toxic deaths occurred. Grade 3–4 toxicities were reported in 40% of patients, consisting of neutropenia (12.5%), neurotoxicity (12.5%), asthenia (9%) and thrombocytopenia (6.5%).

Conclusions:

A+G seems to be effective, with a manageable toxicity profile, after Folfirinox failure in patients with MPA.     

Tumor treating fields in combination with gemcitabine or gemcitabine plus nab-paclitaxel in pancreatic cancer: Results of the PANOVA phase 2 study

Background

Tumor Treating Fields (TTFields), low intensity alternating electric fields with antimitotic activity, have demonstrated survival benefit in patients with glioblastoma. This phase 2 PANOVA study was conducted to examine the combination of TTFields plus chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC).

Respect - A multicenter retrospective study on preoperative chemotherapy in locally advanced and borderline resectable pancreatic cancer

BackgroundNeoadjuvant chemotherapy has become a powerful tool to convert borderline resectable (BRPC) and locally advanced pancreatic cancers (LAPC) into a resectable scenario. However, data analyzing the optimal type of therapy are scarce. In the present multicenter retrospective study, we evaluated the influence of FOLFIRINOX (FFX) and gemcitabine (GEM)-based neoadjuvant therapy on patient prognosis.MethodsData on 239 patients from 7 centers across Europe was gathered using an online database. Patients having received their first cycle of chemotherapy for BRPC/LAPC before 06/2017, with a minimum follow-up of 12 months, were included in the intention-to-treat analysis.ResultsPatients treated with neoadjuvant FFX (n = 135) or gemcitabine + nab-paclitaxel (GNP) (n = 38) had significantly improved radiological response according to RECIST criteria as compared to single-agent GEM (n = 16), with a partial/complete response of 59.3%, 55.3% and 6.25% respectively (p = 0.001). Treatment with FFX (n = 135) and GNP (n = 38) resulted in higher resection rates compared to GEM (73.3%, 81.6% and 43.8%; p = 0.01 and p = 0.005). Regardless of regimen, patients who were resected had significantly prolonged overall survival compared to non-resected patients (p < 0.01). Complete pathological responses (ypT0 ypN0) were predominantly observed with FFX (p = 0.01). Adjuvant GNP in addition to successful neoadjuvant therapy and surgery resulted in a trend towards improved median survival as compared to postoperative observation (47.0 vs. 30.1 months, p = 0.06).ConclusionsRepresenting one of the largest studies published so far, our results reveal that patients with BRPC/LAPC should be offered either FFX or GNP to improve chances of resection and with this also survival.     

Efficacy and tolerance of gemcitabine and nab-paclitaxel in elderly patients with advanced pancreatic ductal adenocarcinoma

BackgroundThe efficacy and safety of gemcitabine and nab-paclitaxel (GnP) among elderly patients with advanced pancreatic ductal adenocarcinoma (PDAC) remains poorly understood. We aimed to evaluate the safety and efficacy of GnP in this setting.Patients and methodsWe retrospectively included all consecutive patients aged ≥65 years with histologically proven PDAC who received at least one cycle of GnP (January 2014 to May 2018) in four academic centers. The primary endpoints were toxicity and overall survival (OS). Secondary endpoints were progression-free survival (PFS) and objective response rate. We compared patients aged ≥ or <75 years.ResultsThe study included 127 patients; among them 42 (33.1%) were aged ≥ 75 years. Fifty-seven and seventy patients received GnP as the first-line and the second-line treatment or beyond, respectively. Sixty-seven patients had at least one grade 3/4 adverse event, the most frequent being neutropenia and peripheral neuropathy. No deaths were related to toxicity. OS (median, 8.0 months; 95% confidence interval (CI), 5.8–10.2) and PFS (median, 5.5 months; 95% CI, 4.8–6.2) were similar for patients aged <75 or ≥75 years in the whole cohort and among patients receiving GnP as the first-line treatment. Cephalic PDAC, liver metastases, hypoalbuminemia, and GnP received beyond the first-line were associated with a significantly shorter OS on the multivariate analysis.ConclusionGnP is well tolerated and effective in elderly patients with advanced PDAC, even patients aged ≥75 years. The data from daily clinical practice are consistent with the results reported with first-line treatment and highlight the relevance of GnP administration in elderly patients.     

Efficacy of chemotherapy for patients with metastatic or recurrent pancreatic adenosquamous carcinoma: A multicenter retrospective analysis

Background/objectivesPancreatic adenosquamous carcinoma (PASC) is a rare variant of pancreatic ductal adenocarcinoma (PDAC). The usual treatment for metastatic or recurrent PASC is systemic chemotherapy in accordance with the PDAC treatment strategy. This study aimed to investigate the efficacy of chemotherapy, especially the benefit of recent combination therapies, in patients with metastatic or recurrent PASC.MethodsWe conducted a multicenter retrospective analysis of 116 patients with metastatic or recurrent PASC treated with first-line chemotherapy between April 2001 and December 2017 at 24 Japanese institutions.ResultsCombination chemotherapies included gemcitabine + nab-paclitaxel (GnP, n = 28), fluorouracil/leucovorin + irinotecan + oxaliplatin (FFX, n = 10), gemcitabine + S-1 (GS, n = 10), and others (n = 9). Monotherapies included gemcitabine (n = 51) and S-1 (n = 8). The median overall survival (OS) was 6.5, 7.3, and 4.3 months for the whole cohort, the combination therapy group, and the monotherapy group, respectively. Multivariate analysis indicated that combination therapy showed a better trend in OS than monotherapy (hazard ratio = 0.68; 95% confidence interval, 0.38–1.20). GnP or FFX were selected in 58.7% of patients after FFX was approved in Japan, and revealed a median OS, median progression-free survival, and objective response rate of 7.3 months, 2.8 months, and 26.9% in GnP and 7.2 months, 2.3 months, and 20.0% in FFX respectively.ConclusionsThis study suggests that combination therapy may be more effective than monotherapy. GnP and FFX showed similar and clinically meaningful efficacy for patients with metastatic or recurrent PASC.