Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study

Garassino, Marina Chiara; Cho, Byoung Chul; Kim, Joo-Hang; Mazières, Julien; Vansteenkiste, Johan; Léna, H.; Jaime, Jesús Corral; Gray, Jhanelle E.; Powderly, John D.; Chouaïd, C.; Bidoli, Paolo; Wheatley‐Price, Paul; Park, Keunchil; Soo, Ross A.; Huang, Yifan; Wadsworth, Catherine; Dennis, Phillip A.; Rizvi, Naiyer A.; Rodríguez, Luis Paz-Ares; Novello, Silvia; Hiret, Sandrine; Schmid, Peter; Laack, Eckart; Califano, Raffaele; Maemondo, Makoto; Kim, Sang‐We; Chaft, Jamie E.; Baz, David Vicente; Berghmans, Thierry; Kim, Dong-Wan; Surmont, Veerle; Reck, Martin; Han, Ji‐Youn; Martin, Esther Holgado; Iniesta, Cristóbal Belda; Oe, Y.; Chella, Antonio; Chopra, Akhil; Robinet, G.; Parra, H. Soto; Thomas, Michael J.; Cheema, Parneet K.; Katakami, Nobuyuki; Su, Wu-Chou; Kim, Young‐Chul; Wolf, Juergen; Lee, Jong-Seok; Sasaki, Hideo; Milella, Michele Stanislaw; García, Inmaculada Ramos; Sibille, Anne; Yokoi, Takashi; Kang, Eun Joo; Atagi, Shinji; Spaeth-Schwalbe, Ernst; Nishio, Makoto; Imamura, Fumio; Gabrail, Nashat; Veillon, Rémi; Derijcke, Sofie; Maeda, Tadashi; Zylla, Dylan; Kubiak, Kendra; Santoro, Armando; Uy, Ma. Noemi; Geater, Sarayut Lucien; Italiano, Antoîne; Kowalski, Dariusz M.; Barlési, Fabrice; Chen, Yuh‐Min; Spigel, David R.; Chewaskulyong, Busyamas; Gómez, Ramón García; Álvarez, Rosa; Yang, Chih-Hsin; Hsia, Te‐Chun; Denis, Fabrice; Sakai, Hiroshi; Vincent, Mark; Goto, Kōichi; Bosch-Barrera, Joaquim; Weiss, Glen J.; Canon, Jean-Luc; Scholz, Christian W.; Aglietta, Massimo; Kemmotsu, Hirotsugu; Azuma, Koichi; Bradbury, Penelope Ann; Feld, Ronald; Chachoua, Abraham; Jassem, Jacek; Juergens, Rosalyn A.; Palmero, Ramón; Malcolm, Albert; Vrindavanam, Nandagopal; Kubota, Keiichi; Waller, Cornelius F.; Waterhouse, David; Coudert, B.; Mark, Z.; Satouchi, Miyako; Chang, Gee‐Chen; Herzmann, Christian; Chaudhry, Arvind; Giridharan, S.; Hesketh, Paul J.; Ikeda, Norihiko; Boccia, Ralph V.; Iannotti, Nichola; Haigentz, Missak; Reynolds, John A.; Querol, J. Marruecos; Nakagawa, Kazuhiko; Sugawara, Shunichi; Tan, Eng Huat; Hirashima, Tomonori; Gettinger, Scott; Kato, Terufumi; Takeda, Koji; Vidal, Òscar; Mohn-Staudner, Andrea; Panwalkar, Amit; Daniel, Davey B.; Kobayashi, Kunihiko; Ladrera, Guia; Schulte, Clemens; Sebastian, Martin; Černovská, Markéta; Ćetković, Helena; Havel, Libor; Pauk, Norbert; Singh, Joginder; Murakami, Shuji; Csőszi, Tibor; Losonczy, György; Price, Allan; Anderson, Ian C.; Iqbal, Mussawar; Torri, V.; Juhász, Erzsébet; Khanani, S.; Koubková, Leona; Levy, Benjamin; Page, Ray D.; Böcskei, Csaba; Crinò, Lucio; Einspahr, David E.; Hagenstad, Christopher; Juat, Necy; Overton, Lindsay; Garrison, Mitchell; Szalai, Zsuzsanna

doi:10.1016/s1470-2045(18)30144-x

Cited by 462 publications

(386 citation statements)

References 27 publications

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“…22 Most recently, in the Supplementary data of a large scale phase 2 study (ATLANTIC) that included 15 ALK-positive NSCLC patients treated with durvalumab as third-line or later therapy, ALK-positive NSCLC patients had a tendency of poor OS and PFS compared to EGFR-positive patients. 23 These findings are consistent with our study.…”

Section: Discussionsupporting

confidence: 93%

“…A retrospective study including six ALK‐positive NSCLC patients found ALK rearrangement to be associated with low overall response rates to PD‐1/PD‐L1 blockade . Most recently, in the Supplementary data of a large scale phase 2 study (ATLANTIC) that included 15 ALK‐positive NSCLC patients treated with durvalumab as third‐line or later therapy, ALK‐positive NSCLC patients had a tendency of poor OS and PFS compared to EGFR‐positive patients . These findings are consistent with our study.…”

Section: Discussionmentioning

confidence: 99%

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The efficacy of immune checkpoint inhibitors in anaplastic lymphoma kinase‐positive non‐small cell lung cancer

et al. 2019

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Background Despite recent advances in treating non‐small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs), their role in ALK‐positive NSCLC patients is unclear. We investigated the efficacy of ICIs in patients with ALK‐positive NSCLC. Methods Between 2011 and 2018, a total of 14 ALK‐positive NSCLC patients treated with ICIs were evaluated retrospectively. Clinicopathologic features including age, PD‐L1 expression, and treatment outcomes were analyzed. RNA expression level and cytolytic activity by ALK positivity were analyzed using The Cancer Genome Atlas (TCGA) and National Cancer Center Research Institute (NCCRI) data sets. Results A total of 13 patients (92.9%) received ALK inhibitors. Patients received a median of three (range 2–8) courses of therapy. The study included nine patients (64.3%) who were PD‐L1‐high (>50%) and four (28.6%) who were PD‐L1‐low (<50%). The objective response rate was 14.3% (2/14). The median progression‐free survival time was 2.18 months (95% confidence interval [CI] 1.13 months‐not reached [NR]). The median overall survival time was 5.67 months (95% CI 3.00 months‐NR). RNA expression levels of CD274 were similar between the ALK‐positive and negative groups in both TCGA and NCCRI datasets. RNA levels of CD8A in both TCGA and NCCRI data sets were nonsignificantly lower in the ALK‐positive group. Cytolytic activity scores including interferon‐γ‐related response were lower in the ALK‐positive group in the NCCRI but not TCGA dataset. Conclusions Despite high PD‐L1‐positive rates, ICIs show limited efficacy in ALK‐positive NSCLC. Decreased interferon‐γ‐related response may underlie these findings.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

The efficacy of immune checkpoint inhibitors in anaplastic lymphoma kinase‐positive non‐small cell lung cancer

et al. 2019

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“…Median sPD-L1 titer was below the LLOQ at the end of infusion on day 1 of dose 1 and again at the end of treatment for all dose groups. At 3 months after the end of treatment, one of one evaluable patient in the 1.0 mg/kg q2w dose group and one of two evaluable patients in the 20 mg/kg q4w dose group had a detectable sPD-L1 titer, with titers of 82.3 and 142, respectively.4 | D ISCUSS I ONOverall, durvalumab was generally well tolerated without DLT in these patients with a range of solid tumor types, including gastric/ gastroesophageal cancer, NSCLC, and other advanced solid tumors.Number of patients with trAE was similar across the dose groups, and consistent with previous reports of PD-1/PD-L1 blockade in general[17][18][19][20][21] and durvalumab specifically;13,15,22,23 the most frequently occurring trAE in accordance with their immune-mediated mechanism were rash and pruritus. Few treatment-related grade ≥3 events occurred in any of the dosing groups.…”

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confidence: 89%

Tolerability and efficacy of durvalumab in Japanese patients with advanced solid tumors

et al. 2019

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Blockade of programmed cell death ligand‐1 with durvalumab has shown efficacy and safety in large, international studies of patients with advanced solid tumors. A phase 1, non‐randomized, open‐label multicenter study was initiated to evaluate durvalumab in a Japanese population. The first part of this study used a standard 3 + 3 dose‐escalation design to determine the optimal dosing schedule of durvalumab. Primary objective was evaluation of safety and tolerability of durvalumab monotherapy. Secondary objectives were to evaluate maximum tolerated dose ( MTD ), immunogenicity, pharmacokinetics, and efficacy. Twenty‐two patients (median age, 61.5 years; range, 41‐76; 64% male) received durvalumab at doses of 1, 3, or 10 mg/kg every 2 weeks (q2w), 15 mg/kg q3w, or 20 mg/kg q4w. Twenty patients discontinued before completing 12 months of treatment as a result of progressive disease and two due to adverse events ( AE ). The most common treatment‐related AE (tr AE ) were rash (18%) and pruritus (14%); two patients had grade ≥3 tr AE including one patient each with hyponatremia and hypothyroidism. No patient experienced a dose‐limiting toxicity ( DLT ) during the DLT evaluation period and the MTD was not identified. There were no AE leading to a fatal outcome during study treatment. Durvalumab showed dose‐proportional pharmacokinetics across the 1‐20 mg/kg dose range; incidence of positive titers for antidrug antibodies was 9%. One patient with lung cancer had a partial response and disease control rate at 12 weeks was 36%. In conclusion, durvalumab at the doses and regimens evaluated was safe and well tolerated in Japanese patients with advanced solid tumors.

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“…These results suggested the efficacy of atezolizumab in the third‐line treatment for patients with advanced NSCLC. In another phase II trial (ATLANTIC), the ORR of durvalumab in patients with NSCLC with EGFR and ALK positivity and ≥25% of tumor cells expressing PD‐L1 was 12.2%, which was lower than those with EGFR and ALK negativity (16.4%) or those with ≥90% PD‐L1 expression of tumor cells (30.9%) . Because the clinical trials in this stage are limited, the efficacy of PD‐1/PD‐L1 blockade therapy might be warranted with more phase III trials.…”

Section: Pd‐1/pd‐l1 Blockade Therapy In Advanced Nsclcmentioning

confidence: 99%

PD-1/PD-L1 Blockade Therapy in Advanced Non-Small-Cell Lung Cancer: Current Status and Future Directions

2019

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This article summarizes the latest clinical applications of PD‐1/PD‐L1 blockade therapy in advanced non‐small cell lung cancer (NSCLC) worldwide and in China, reporting the bottlenecks related to the use of this therapy in clinic. An exploration of the underlying mechanism of PD‐1/PD‐L1 blockade therapy and biomarker identification will maximize the application of immune checkpoint inhibitors in advanced NSCLC and facilitate bedside‐to‐bench studies in cancer immunotherapy.

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Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study

Abstract: AstraZeneca.

Cited by 462 publications

References 27 publications

The efficacy of immune checkpoint inhibitors in anaplastic lymphoma kinase‐positive non‐small cell lung cancer

The efficacy of immune checkpoint inhibitors in anaplastic lymphoma kinase‐positive non‐small cell lung cancer

Tolerability and efficacy of durvalumab in Japanese patients with advanced solid tumors

PD-1/PD-L1 Blockade Therapy in Advanced Non-Small-Cell Lung Cancer: Current Status and Future Directions

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