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ASCO 2025 | How can we treat patients with NSCLC who progress on EGFR TKIs?
Tony Mok, MD, Chinese University of Hong Kong, Hong Kong, China, comments on the challenges faced by patients with non-small cell lung cancer (NSCLC) who failed first line EGFR TKIs, highlighting the problem of heterogeneity in the underlying mechanisms of resistance, which can involve multiple mechanisms such as transformation to small cell lung cancer. A lack of a single biomarker for selection of optimal therapy limits treatment options, and ongoing studies, including the SACHI study (NCT05015608), aim to identify subgroups of patients that can benefit from specific therapies. This interview took place during the 2025 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
For patients who failed the first line EGFR TKI, the problem is heterogeneity. There is actually not a single mechanism, but it could involve multiple mechanisms, for which it will include transformation to small cell lung cancer, C797 as a mutation, magnification, and also the other uncommon mutation, plus a whole bunch, about 40 to 60 percent that’s unknown. So now we have chemotherapy or we may add chemotherapy together with amivantamab as per MARIPOSA-2 study but we’re still not able to use a biomarker selection to look into the optimal therapy for this population...
For patients who failed the first line EGFR TKI, the problem is heterogeneity. There is actually not a single mechanism, but it could involve multiple mechanisms, for which it will include transformation to small cell lung cancer, C797 as a mutation, magnification, and also the other uncommon mutation, plus a whole bunch, about 40 to 60 percent that’s unknown. So now we have chemotherapy or we may add chemotherapy together with amivantamab as per MARIPOSA-2 study but we’re still not able to use a biomarker selection to look into the optimal therapy for this population. Now for that actually in ASCO this year there’s also a study on SACHI which is a study from China looking on MET amplification continual osimertinib plus a oral MET inhibitor. So those are the kind of data we need to be able to cut the different patient into subgroups, such as we can see that the best therapy for them.
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Disclosures
Employment – The Chinese University of Hong Kong
Leadership – AstraZeneca; Aurora Tele-Oncology Platform; HUTCHMED; Insighta Holdings Limited
Stock and Other Ownership Interests – Alentis Therapeutics; AstraZeneca; Aurora Tele-Oncology Platform; Biolidics; D3 Bio; HUTCHMED; Lunit; Prenetics
Honoraria – Abbvie; ACEA Pharmaceutical Research; Adagene; Alpha Biopharma; Amgen; Amoy Diagnostics; AnHeart Therapeutics; AstraZeneca; AVEO; BeiGene; Berry Oncology; Blueprint Medicines; Boehringer Ingelheim; Bristol-Myers Squibb; C4 Therapeutics; CStone Pharmaceuticals; Curio Science; D3; Da Volterra; Daiichi Sankyo/UCB Japan; Daz Group; Eisai; Fishawack Facilitate; Gilead Sciences; GLG’s Healthcare; Gritstone Bio; Guardant Health; Hengrui Therapeutics; Ignyta; Illumina; Incyte; Inivata; InMed; IQVIA; Janssen; Jiahui Holdings Co; Lakeshore Biotechnology; Lilly; Lucence; Lucence; MD Health Brazil,; Medscape; Merck; Merck Sharp & Dohme; MiRXES; Novartis; Novocure; Omega Therapeutics; Origimed; PeerVoice; Permanyer Publications; Pfizer; Physicans’ Education Resource; Prenetics; Prime Oncology; Qiming Development (HK) Ltd.; Regeneron; Research to Practice; Roche; Sanofi Aventis GmbH; SFJ Pharmaceutical Ltd; Shanghai BeBirds Translation & Consulting; Shanghai Promedican Pharmaceuticals Co., Ltd; Simcere of America Inc.; Summit Therapeutics Sub, Inc.; Suzhou Liangyihui Network Technology; Synergy Research; Taiho Pharmaceutical; Takeda; Tigermed; touchIME; Vertex; Virtus Medical Group; Xencor; Yuhan
Consulting or Advisory Role – Abbvie; ACEA Pharmaceutical Research; Adagene; Alpha Biopharma; Amgen; Amoy Diagnostics; AstraZeneca; Bayer HealthCare Pharmacuticals; BeiGene; BerGenBio; Berry Oncology; Blueprint Medicines; Boehringer Ingelheim; Bowtie Life Insurance Company; Bridgebio; Bristol-Myers Squibb; C4 Therapeutics; Cirina; Covidien/Medtronic; Covidien/Medtronic; CStone Pharmaceuticals; Curio Science; D3; Da Volterra; Daiichi Sankyo/UCB Japan; Eisai; Elevation Oncology; Fishawack Facilitate; G1 Therapeutics; geneDecode; Genentech; Gilead Sciences; Gritstone Bio; Guardant Health; Hengrui Therapeutics; HUTCHMED; Ignyta; Imagene AI Ltd.; Incyte; Inivata; IQvia; Janssen; Lakeshore Biotechnology; Lilly; Loxo; Lucence; Lunit; Medtronic; Merck Serono; Merck Sharp & Dohme; Mirati Therapeutics; MiRXES; Novartis; Omega Therapeutics; OrigiMed; OSE Immunotherapeutics; Pfizer; Prenetics; PrIME Oncology; Puma Biotechnology; Qiming Development (HK) Ltd.; Regeneron; Roche; SFJ Pharmaceuticals Group; Simcere; Summit Therapeutics; Synergy Research; Takeda; Tigermed; Vertex; Virtus Medical Group; Yuhan
Research Funding – AstraZeneca (Inst); Boehringer Ingelheim (Inst); Bristol-Myers Squibb (Inst); G1 Therapeutics (Inst); Merck Serono (Inst); Merck Sharp & Dohme (Inst); Novartis (Inst); Pfizer (Inst); Roche (Inst); SFJ Pharmaceuticals Group (Inst); Takeda (Inst); Xcovery (Inst)
Travel, Accommodations, Expenses – Abbvie; Astrazeneca; Daiichi Sankyo; Liangyihui; MiRXES; Novartis; Pfizer; Pfizer; Roche; Zai Lab
