Rechallenge for Patients With <i>RAS</i> and <i>BRAF</i> Wild-Type Metastatic Colorectal Cancer With Acquired Resistance to First-line Cetuximab and Irinotecan

Cremolini, Chiara; Rossini, Daniele; Dell’Aquila, Emanuela; Lonardi, Sara; Conca, Elena; Re, Marzia Del; Busico, Adele; Pietrantonio, Filippo; Danesi, Romano; Aprile, Giuseppe; Tamburini, Emiliano; Barone, Carlo; Masi, Gianluca; Pantano, Francesco; Pucci, Francesca; Corsi, Domenico; Pella, Nicoletta; Bergamo, Francesca; Rofi, Eleonora; Barbara, C.; Falcone, Alfredo; Santini, Daniele

doi:10.1001/jamaoncol.2018.5080

Cited by 287 publications

(251 citation statements)

References 36 publications

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“…However, the benefit of retreatment with such antibodies has been unclear [64]. A recent phase II CRICKET study examined the possibility of rechallenge with antibodies to EGFR in the third-line setting for RAS wild-type mCRC [65]. The study recruited patients, who benefited from first-line treatment with anti-EGFR antibody cetuximab before the development of resistance and administration of chemotherapy as a second-line treatment.…”

Section: Advantages Of Trastuzumab Deruxtecanmentioning

confidence: 99%

Emerging Targeted Therapies for HER2 Positive Gastric Cancer That Can Overcome Trastuzumab Resistance

Mitani

Kawakami

2020

Cancers

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Trastuzumab, a monoclonal antibody to human epidermal growth factor receptor 2 (HER2), has improved survival in patients with HER2-positive advanced gastric or gastroesophageal junction cancer (AGC). The inevitable development of resistance to trastuzumab remains a problem, however, with several treatment strategies that have proven effective in breast cancer having failed to show clinical benefit in AGC. In this review, we summarize the mechanisms underlying resistance to HER2-targeted therapy and outline past and current challenges in the treatment of HER2-positive AGC refractory to trastuzumab. We further describe novel agents such as HER2 antibody-drug conjugates that are under development and have shown promising antitumor activity in early studies. basis of these results, trastuzumab was approved for AGC with a high HER2 expression level, and trastuzumab-containing regimens are now a standard option for the first-line treatment of such patients, who accounted for 7% to 17% of all individuals with gastric cancer [3-5]. Derivatives of the ToGA Regimen in the First-Line SettingThe ToGA trial adopted a regimen of cisplatin combined with either 5-fluorouracil (5-FU) or capecitabine, whereas subsequent prospective studies found similar treatment outcomes with regimens containing oxaliplatin or tegafur-gimeracil-oteracil (S-1). In a single-arm, nonrandomized phase II trial (HER2-based strategy in stomach cancer (HERBIS)-1) performed in Japan [6], trastuzumab in combination with S-1 plus cisplatin yielded a confirmed ORR of 68%, with a median OS and a median PFS of 16.0 and 7.8 months, respectively, in HER2-positive AGC patients with measurable lesions, with these results being similar to those of the ToGA trial [2]. Similar efficacy was also apparent in AGC patients without measurable lesions (HERBIS-1B study) [7]. Three phase II studies that assessed the combination of trastuzumab with capecitabine plus oxaliplatin reported a median OS, a median PFS, and an ORR of 13.8 to 21.0 months, 7.1 to 9.8 months, and 46.7% to 67.3%, respectively [8][9][10]. Trastuzumab in combination with S-1 plus oxaliplatin was also shown to provide a similar treatment outcome in a phase II study, with a median OS, a median PFS, and an ORR of 18.1 months, 8.8 months, and 70.7%, respectively [11]. A meta-analysis of data from these trials revealed that S-1 or oxaliplatin can substitute effectively for capecitabine or 5-FU or for cisplatin, respectively [12].Immune checkpoint inhibitors such as antibodies to programmed cell death-1 (PD-1) have recently revolutionized treatment strategies for advanced cancer. Given that trastuzumab was found to stimulate T cell responses [13], the combination of trastuzumab-containing regimens with antibodies to PD-1 is receiving attention. A phase II study including 37 patients with HER2-positive AGC treated in the first-line setting with capecitabine, oxaliplatin, and trastuzumab in combination with the anti-PD-1 antibody pembrolizumab reported an ORR of 83%, with a median PFS of 11.4 months and a median ...

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Section: Advantages Of Trastuzumab Deruxtecanmentioning

confidence: 99%

Emerging Targeted Therapies for HER2 Positive Gastric Cancer That Can Overcome Trastuzumab Resistance

Mitani

Kawakami

2020

Cancers

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“…A longer oxaliplatin‐free interval may permit recovery from any persistent peripheral neuropathy. Decay of mutant RAS over time, as demonstrated in circulating tumor DNA analysis, also suggests that extending the time interval between an initial EGFR inhibitor and rechallenge may enhance patient benefit 31‐33 …”

Section: Practical Guidancementioning

confidence: 99%

Trifluridine/tipiracil: A practical guide to its use in the management of refractory metastatic colorectal cancer in Australia

Price

Burge

Chantrill

et al. 2020

Asia-Pac J Clncl Oncology

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Trifluridine/tipiracil is available on the Australian Pharmaceutical Benefits Scheme for the treatment of patients with metastatic colorectal cancer (mCRC) previously treated with, or not considered candidates for, fluoropyrimidine-, oxaliplatin-and irinotecan-based chemotherapies, antivascular endothelial growth factor agents and anti-epidermal growth factor receptor agents. This article reviews trifluridine/tipiracil clinical data and presents practical information on its use in the management of refractory mCRC in Australia. Whereas the primary mechanism of action of fluoropyrimidines such as fluorouracil (5-FU) and capecitabine is enzyme inhibition of nucleotide synthesis, trifluridine/tipiracil primarily acts by incorporation into DNA, resulting in DNA dysfunction.Trifluridine/tipiracil has activity in patients with 5-FU-resistant tumors and can be considered in patients with prior intolerance or toxicity to 5-FU. In the pivotal phase III RECOURSE trial evaluating trifluridine/tipiracil in chemotherapy-refractory mCRC, efficacy benefits were observed across all a priori prognostic subgroups including those defined by age (≥65 and ≥75 years), geographical origin, primary tumor site or KRAS status. Trifluridine/tipiracil therapy benefits appropriately selected patients who have an ECOG performance status of 0 or 1, with no more than mild hepatic impairment or mild-to-moderate renal impairment, and who are capable of adhering to oral therapy safely. Appropriate dosing, monitoring for adverse events and effective management of side effects are essential.

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“…89 In line with this hypothesis, the results of CRICKET, a small single-arm proof-of-concept prospective study of rechallenge with cetuximab and irinotecan, have recently been published. 90 Twenty-seven patients with RAS and BRAF WT mCRC, who had at least a PR and PFS of 6 months or more after first-line cetuximab plus chemotherapy, were enrolled. Interestingly, a post hoc analysis revealed that all patients who achieved a PR had RAS WT tumors at the baseline liquid biopsy testing for ctDNA before cetuximab plus irinotecan rechallenge.…”

Section: Novel Approaches For Optimizing the Efficacy Of Anti-egfr Thmentioning

confidence: 99%

“…Interestingly, a post hoc analysis revealed that all patients who achieved a PR had RAS WT tumors at the baseline liquid biopsy testing for ctDNA before cetuximab plus irinotecan rechallenge. 90 Several trials of anti-EGFR rechallenge therapies are currently on-going (Table 3).…”

Section: Novel Approaches For Optimizing the Efficacy Of Anti-egfr Thmentioning

confidence: 99%

Implementing anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer: challenges and future perspectives

et al. 2020

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Epidermal growth factor receptor (EGFR) inhibitors are valuable therapeutics in metastatic colorectal cancer (mCRC). Anti-EGFR monoclonal antibodies (MoAbs), such as cetuximab or panitumumab, in combination with chemotherapy are effective treatment options for patients with RAS and BRAF wild-type mCRC. Nevertheless, several issues are still open concerning the optimal use of anti-EGFR drugs in the continuum of care of mCRC. Novel approaches for increasing the efficacy of anti-EGFR therapies include better molecular selection of EGFR-dependent mCRC, intensification of chemotherapy, combination of anti-EGFR MoAbs and immune checkpoint inhibitors, and reintroduction of EGFR blockade or 'rechallenge' in selected patients who have previously responded to anti-EGFR MoAb therapy. An extensive translational research program was conducted in the Cetuximab After Progression in KRAS wIld-type colorectal cancer patients-Gruppo Oncologico dell' Italia Meridionale (CAPRI-GOIM) study with the aims of determining which subgroups of patients could benefit from the continuous inhibition of EGFR, from evaluating the role of liquid biopsy-based and its concordance with tissue-based molecular testing, and from investigating novel potential mechanisms of resistance to anti-EGFR therapies. In this review, we summarize the translational and clinical findings of the CAPRI-GOIM program in the context of the current knowledge of therapeutic strategies and of ongoing research on more appropriate uses of anti-EGFR therapies in RAS and BRAF wild-type mCRC patients.

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Rechallenge for Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer With Acquired Resistance to First-line Cetuximab and Irinotecan

Cited by 287 publications

References 36 publications

Emerging Targeted Therapies for HER2 Positive Gastric Cancer That Can Overcome Trastuzumab Resistance

Emerging Targeted Therapies for HER2 Positive Gastric Cancer That Can Overcome Trastuzumab Resistance

Trifluridine/tipiracil: A practical guide to its use in the management of refractory metastatic colorectal cancer in Australia

Implementing anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer: challenges and future perspectives

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