Impact Of First-line Chemotherapy Research Articles

P-74 The impact of first-line chemotherapy in elderly patients with advanced pancreatic cancer: A mono-institutional retrospective study

Pancreatic cancer median age at diagnosis is 70 years old. However, elderly patients (pts) are underrepresented in randomized clinical trials (RCTs) and chemotherapy efficacy and safety data in this population are limited. Herein, we present a retrospective analysis of an elderly population treated at our institution, investigating the role of baseline clinical factors in guiding treatment decision-making. Pts aged ≥70 years old receiving first-line chemotherapy for advanced pancreatic cancer (APC) were included in the analysis. The primary end-points were progression-free survival (PFS) and overall survival (OS). The following variables were collected: gender; age (≥ 70 and < 75 years vs ≥ 75 years); baseline ECOG PS (0-1 vs 2-3); site of primary tumor (head/uncinate process vs body/tail); disease stage (locally advanced vs metastatic); baseline CA 19.9 (< vs ≥ 200); chemotherapy regimen; comorbidities (yes vs no); number of comorbidities (0-1 vs ≥ 2). Univariate and multivariate analysis for PFS and OS were performed. A total of 169 APC pts aged ≥70 years old, receiving first-line chemotherapy between March 2015 and August 2020, were included in the analysis. The median age was 76 years (70-89), ECOG PS was 0-1 in 77% of pts; 70% were metastatic; 70% of pts had a head/uncinate process primary tumor; 25% had baseline CA 19.9 ≥ 200; 9.4% of pts had no comorbidities and 50% had ≥2 comorbidities. The majority of pts received gemcitabine nab-paclitaxel (60%), other regimes included gemcitabine (28%), FOLFIRINOX (5%), capecitabine (4%), FOLFOX (2%) and FOLFIRI (1%). The overall population median PFS and OS were 6.5 (median follow-up 19.1 months) and 11 months (median follow-up 21.8 months), respectively. Out of 164 pts evaluable, 38 (23%) pts achieved a partial response and 58 (35%) a stable disease, with a disease control rate of 58%. At the multivariate analysis, ECOG PS 0-1 was independently associated with both improved PFS (p=0.005) and OS (p=0.0084). At the multivariate analysis for PFS, locally advanced stage was also significantly associated with better PFS (p=0.036). In pts with ECOG PS 0-1 vs 3-4 the median PFS was 6.7 vs 3.3 months (p=0.0004) and median OS was 11.3 vs 5.5 moths (p=0.003), respectively. Despite the retrospective nature of the analysis and the limited sample size, we observed that elderly APC pts can benefit from first-line treatment, achieving survival outcomes comparable to the ones reported for younger pts in RCTs. On the basis of our results, the baseline ECOG PS can be considered a prognostic factor for both PFS and OS. In conclusion, elderly pts should not be precluded from active treatment, and careful patient selection, mainly according to baseline ECOG PS, should guide treatment indication.

The impact of first-line chemotherapy in elderly patients (pts) with advanced pancreatic cancer (APC): A mono-institutional retrospective study.

e16229 Background: Pancreatic cancer median age at diagnosis is 70 years old. However, elderly pts are underrepresented in randomized clinical trials (RCTs) and chemotherapy efficacy and safety data in this population are limited. Herein, we present a retrospective analysis of an elderly population treated at our Institution, investigating the role of baseline clinical factors in guiding treatment decision making. Methods: Pts aged ≥70 years old receiving a first-line chemotherapy for APC were included in the analysis. The primary end-points were progression-free survival (PFS) and overall survival (OS). The following variables were collected: gender; age (≥ 70 and &lt; 75 years vs ≥ 75 years); baseline ECOG PS (0-1 vs 2-3); site of primary tumor (head/uncinate process vs body/tail); disease stage (locally advanced vs metastatic); baseline CA 19.9 ( &lt; vs ≥ 200); chemotherapy regimen; comorbidities (yes vs no); number of comorbidities (0-1 vs ≥ 2). Univariate and multivariate analysis for PFS and OS were performed. Results: A total of 169 APC pts aged ≥70 years old, receiving first-line chemotherapy between March 2015 and August 2020, were included in the analysis. The median age was 76 years (70-89), ECOG PS was 0-1 in 77% of pts; 70% were metastatic; 70% of pts had a head/uncinate process primary tumor; 25% had baseline CA 19.9 ≥ 200; 9.4% of pts had no comorbidities and 50% had ≥2 comorbidities. The majority of pts received gemcitabine nab-paclitaxel (60%), other regimes included gemcitabine (28%), FOLFIRINOX (5%), capecitabine (4%), FOLFOX (2%) and FOLFIRI (1%). The overall population median PFS and OS were 6.5 (median follow-up 19.1 months) and 11 months (median follow-up 21.8 months), respectively. Out of 164 pts evaluable, 38 (23%) pts achieved a partial response and 58 (35%) a stable disease, with a disease control rate of 58%. At the multivariate analysis, ECOG PS 0-1 resulted independently associated both with improved PFS (p 0.005) and OS (p 0.0084). At the multivariate analysis for PFS, also locally advanced stage resulted significantly associated with better PFS (p = 0.036). In pts with ECOG PS 0-1 vs 3-4 the median PFS was 6.7 vs 3.3 months (p 0.0004) and median OS was 11.3 vs 5.5 moths (p 0.003), respectively. Conclusions: Despite the retrospective nature of the analysis and the limited sample size, we observed that elderly APC pts can benefit from a first-line treatment achieving survival outcomes comparable to the one reported for younger pts in RCTs. On the basis of our results, the baseline ECOG PS can be considered a prognostic factor for both PFS and OS. In conclusion, elderly pts should not be precluded from an active treatment and careful patient selection, mainly according to baseline ECOG PS, should guide treatment indication.

Oligometastatic colorectal cancer: prognosis, role of locoregional treatments and impact of first-line chemotherapy—a pooled analysis of TRIBE and TRIBE2 studies by Gruppo Oncologico del Nord Ovest

BackgroundOligometastatic disease (OMD) identifies tumours with limited metastatic spread. OMD definition is not univocal and no data from clinical trials are available about the prognostic effect of OMD in metastatic colorectal cancer (mCRC), the impact of locoregional treatments (LRTs) and the effect of chemotherapy intensification in these patients. The role of tumour burden (TB) in driving therapeutic choices is also debated. Patients and methodsWe performed a pooled analysis of phase III TRIBE and TRIBE2 studies comparing FOLFOXIRI/bevacizumab (bev) to doublets (FOLFOX or FOLFIRI)/bev. Patients were grouped in OMD versus non-OMD based on the European Society for Medical Oncology definition. Among patients with OMD, those with OMD/low TB were compared with all the others. ResultsOf 1187 patients enrolled, 1096 were classified as OMD (N = 312 [28%]) or non-OMD (N = 784 [72%]). Among patients with OMD, 126 (40%) were OMD/low TB. OMD was associated with longer progression-free survival (14.0 versus 10.1 months; p < 0.01) and overall survival (38.2 versus 22.0 months; p < 0.01). These results were confirmed in multivariable models. The benefit provided by FOLFOXIRI/bev compared with doublets/bev did not differ in accordance with OMD and TB (p for interaction >0.05). Patients with OMD underwent LRTs more frequently (p < 0.01) and those with OMD/low TB had higher chance to undergo LRTs after the first progression (p < 0.01). ConclusionsOMD is a positive prognostic factor in mCRC. The benefit from the upfront treatment intensification is independent of the metastatic spread extent and TB. LRTs should be highly considered in these patients, mainly during the first-line therapy but also at later stages of treatment history in selected cases.

Treating Patients With EGFR-Sensitizing Mutations: First Line or Second Line—Is There a Difference?

First-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) is a standard treatment for patients with activating EGFR mutations. Six randomized studies have demonstrated consistent improvement in tumor response rate and progression-free survival over platinum-based combination chemotherapy. The only reason to consider EGFR TKI as second-line therapy is that none of the six comparative studies has shown improvement in overall survival, which can be explained by the high proportion of patients from the chemotherapy arm crossing over to the EGFR TKI arm on progression. It is true that patients with EGFR mutations may benefit from second-line EGFR TKI therapy, but we cannot conclude that the benefit is either equal to or inferior to first-line EGFR TKI therapy. To date, there are no direct comparative data between first- and second-line EGFR TKI in patients with activating EGFR mutations. Tumor response rates to second-line EGFR TKI have been inconsistent, which could potentially be explained by the impact of first-line chemotherapy on the abundance of tumor cells with activating EGFR mutations. However, numerous arguments, including assurance on drug exposure, improvement in quality of life, better tolerance by patients with poor performance status, and deferral of whole-brain radiation therapy for patients with brain metastasis, support the general application of first-line EGFR TKI.

Use of the Monoclonal Antibody Anti-HER2 Trastuzumab in the Treatment of Metastatic Breast Cancer

This open controlled prospective study aimed at evaluating the medical and economical impact of first line chemotherapy for metastatic breast cancer (MBC). Two groups of HER +++ MBC patients were compared: 26 were treated by a combination of trastuzumab and paclitaxel in 4 "prescriber" centers (group A) and 19 patients were treated by any chemotherapy without addition of trastuzumab, in 6 control centers (group B). The cost of chemotherapy and related hospitalizations was taken into account during the first 8 cycles. Forty-five patients, mean age 51 years have been included. The objective response rate was significantly higher in group A (42% vs. 6%, P = 0.036). The median overall survival was 17 months longer in the group A (29 vs. 12 months). The median progression free survival rate was 12.2 months longer in the group A (19 vs. 7 months). The 1-year survival rate was 85% in the group A and 47% in the group B. The mean overall care cost was 33.271 euro per patient in group A versus 11.191 euro per patient in group B. The additional cost per saved year of life expressed as the incremental cost-effectiveness ratio is 15.370 euro 2002. The related additional cost seems affordable for an European health care system and justifies the recommendation for its use in the subpopulation overexpressing HER2.