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. 2022 Dec 7;25(1):37.
doi: 10.3892/ol.2022.13623. eCollection 2023 Jan.

Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer

Santiago Cabezas-Camarero  1 , Salomé Merino-Menéndez  2 , María Nieves Cabrera-Martín  3 , Miguel J Sotelo  4   5   6 , José Carlos Plaza-Hernández  7 , Farzin Falahat  8 , María Cruz Iglesias-Moreno  9 , Pedro Pérez-Segura  1
Affiliations

Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer

Santiago Cabezas-Camarero et al. Oncol Lett. .

Abstract

Novel chemo-immunotherapy (chemo-IO) combinations should be evaluated, which may be suitable for cisplatin-unfit or fluoropyrimide-ineligible patients with recurrent or metastatic squamous cell carcinoma of head and neck (R/M SCCHN) to guarantee higher and deeper responses than IO alone. The aim of the present study was to review our experience using pembrolizumab-carboplatin-paclitaxel (pembro + CP) in patients with R/M SCCHN. This was a retrospective study of patients with R/M SCCHN who received pembro + CP in any-line via a compassionate-use program. The present study evaluated safety using Common Terminology Criteria for Adverse Events v4.0, compliance, overall response rate (ORR) and disease control rate (DCR) using Response Evaluation Criteria in Solid Tumors 1.1, duration of treatment, progression-free survival (PFS) and overall survival (OS). Between March 2020 and August 2021, 10 patients were identified (median age, 64 years; female, 60%; Eastern Cooperative Oncology Group 2, 80%). A total of 8 patients received pembro + 3-weekly carboplatin-paclitaxel (3wkCP). A total of 2 patients received pembro + weekly carboplatin-paclitaxel (wkCP). Patients received a median of 3 lines (range, 0-6) of systemic therapy prior to pembro + CP and 80% received IO in previous lines. Grade 1-2 adverse events (AEs) occurred in 100% of patients. Grade 3-5 AEs occurred in 30% of patients [all grade 3 (anemia, neutropenia, thrombopenia, hypertension)]. The mean numbers of pembro + wkCP and pembro + 3wkCP cycles were 2.5 and 6. The ORR (n=7) was 14% (1/7) with one complete response. The DCR was 43% (3/7). The median PFS (n=7) and OS (n=10) times since pembro + CP were 5 months (95% CI, 1-9) and 6 months (95% CI, 0.5-14), respectively. In this small retrospective series of heavily pretreated patients, pembro + CP was well tolerated, and compliance was high. Studies should be conducted to prospectively evaluate the safety and efficacy of this combination in patients with R/M SCCHN.

Keywords: anti-programmed cell death protein 1; carboplatin; chemoimmunotherapy; head and neck cancer; paclitaxel; pembrolizumab.

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Conflict of interest statement

SCC has worked as a consultant and as a Speaker's Bureau representative for Bristol-Myers Squibb, Merck and MSD, and has received grant/research support from clinical trials with AstraZeneca, MSD and Merck. PPS has also worked as a consultant and as a Speaker's Bureau representative for Bristol-Myers Squibb, Merck and MSD, and received grant/research support from clinical trials with Bristol-Myers Squibb, AstraZeneca and MSD. The remainder of the authors declare that they have no competing interests.

Figures

Figure 1.
Figure 1.
(A) OS (blue) and DOT (orange) since the start of pembro + CP for each individual patient. (B) OS since the start of first-line treatment for each individual patient. Time is shown in months. Patient 8 died from COVID19 pneumonia 2 weeks after starting pembro + CP. DOT, duration of treatment; OS, overall survival; pembro + CP, pembrolizumab-carboplatin-paclitaxel.
Figure 2.
Figure 2.
Treatment history since the start of pembro + CP in 2 patients. (A) Patient 3 and (B) patient 10 (see Table V for more information on each of the cases). Yellow arrows indicate the tumor lesions in each patient. AWD, alive with disease; CT, computed tomography; pembro + CP, pembrolizumab-carboplatin-paclitaxel; PET, positron emission tomography.
Figure 3.
Figure 3.
(A) Kaplan-Meier curves for PFS and OS in the whole population for pembro + CP and OS since first-line of therapy. (B) Kaplan-Meier curves for PFS and OS in the 8 patients treated with pembro + 3wkCP. 3wkCP, 3-weekly carboplatin-paclitaxel; OS, overall survival; pembro + CP, pembrolizumab-carboplatin-paclitaxel; PFS, progression-free survival.
Figure 4.
Figure 4.
Treatment history since the start of first-line therapy in the 10 patients treated with pembro + CP. Segmented bars show different colors that correspond to the different therapeutic regimens used during the treatment journey of each patient. The colors are as follows: Violet, cetuximab-based chemotherapy; blue, nivolumab-based treatment; yellow, pembrolizumab + CP; and green, pembrolizumab alone. Time is shown in months. Patient 4 received 6 cycles of pembro + 3-weekly carboplatin-paclitaxel (appears in yellow) followed by maintenance therapy with pembrolizumab (appears in green; still ongoing), which has been described in a previous publication (19). Patient 8 died from COVID19 pneumonia 2 weeks after starting pembro + CP. CIS-C, weekly cisplatin + weekly cetuximab; CT, clinical trial; N, nivolumab; NC, nivolumab + weekly cetuximab; P (green), pembrolizumab; PC (violet), weekly paclitaxel and cetuximab; PC (green), pembrolizumab + weekly cetuximab; PCC (violet), weekly carboplatin, paclitaxel and cetuximab; PCP, pembro + CP; PDL1, anti-PDL1 agent; pembro + CP, pembrolizumab-carboplatin-paclitaxel; TPEx, 3-weekly docetaxel + 3-weekly platinum + weekly cetuximab.
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