Dr. Prantesh Jain and Dr. Joshua Sabari delved into the quite a few advances in NSCLC following 2025 ASCO, highlighting the RESILIENT-1 and NeoADAURA trials.
Dr. Prantesh Jain and Dr. Joshua Okay. Sabari defined that there have been quite a few advances within the non-small cell lung most cancers (NSCLC) therapy area following the 2025 ASCO Annual Assembly, highlighting knowledge from the RESILIENT-1 and NeoADAURA trials.
Jain sat down for an interview with our host, Sabari, to focus on what these developments in care imply for sufferers with NSCLC, delving into the topline takeaways, together with efficacy and security. To listen to extra from Sabari and Jain, don’t overlook to learn extra about their dialog on small cell lung most cancers! Or, you possibly can watch extra from the pair right here.
Sabari is the editor in chief of CURE. He additionally serves as an assistant professor within the Division of Medication at NYU Grossman College of Medication and director of Excessive Reliability Group Initiatives at Perlmutter Most cancers Middle. Jain is a medical oncologist at Roswell Park Complete Most cancers Middle, in Buffalo, New York, the place he additionally serves as an assistant professor of Oncology within the Division of Medication. He additionally works on the State College of New York at Buffalo as a medical assistant professor.
Sabari: Howdy. I am Dr. Joshua Okay. Sabari, a thoracic medical oncologist at NYU Langone Well being Perlmutter Most cancers Middle, in New York, and I am additionally the editor in chief of CURE. I am actually excited as we speak to be joined by Dr. Jain, a thoracic medical oncologist.
Dr. Jain, please introduce your self.
Jain: Hello, thanks for having me. I am Dr. Prantesh Jain, a thoracic oncologist at Roswell Park Most cancers Middle, and I am excited to be right here to share updates in lung most cancers from ASCO this yr.
Sabari: Wanting on the NSCLC area, which is way extra frequent than small cell lung most cancers, and makes up about 85% of all lung most cancers identified. Inform me, Dr. Jain, what had been you enthusiastic about at ASCO 2025?
Jain: One very fascinating examine we had been anticipating for sufferers with EGFR exon 20 insertion mutation NSCLC was the RESILIENT-1 examine. This examine primarily examined the oral drug zipalertinib, which is a small molecule, potent EGFR exon 20 TKI.
To offer some context, though EGFR exon 20 mutated NSCLC includes roughly 1% to 2% of instances, these tumors are usually proof against first- and second-generation TKIs and in addition don’t present a superb response to immunotherapy combos. The RESILIENT-1 trial is a part 1/2 examine of zipalertinib, an oral EGFR TKI with very promising central nervous system (CNS) penetration. It enrolled 244 sufferers with superior NSCLC harboring these mutations.
The 2 key cohorts had been: sufferers post-platinum chemotherapy who had not obtained any prior exon 20 focused remedy, and people who had obtained prior platinum and prior focused remedy. Zipalertinib was administered at 100 milligrams orally twice day by day. Sufferers with secure and untreated mind metastases had been permitted on this examine.
The confirmed general response fee was 35%, with a median length of response near 9 months. Within the subgroup evaluation, responses within the platinum-only group had been round 40%, with a length of response of 8.8 months. What was significantly encouraging to notice was that the response fee in sufferers post-Rybrevant (amivantamab-vmjw) was nonetheless round 30%, with a length of response of 14.7 months. For sufferers who had obtained different oral TKIs beforehand, the response fee was a lot decrease, as anticipated, at roughly 14%, with a length of response of 4.2 months.
The drug demonstrated exercise in sufferers with mind metastases, reaching a 31% response fee on this group. The security profile was fairly acceptable; the most typical grade 3 or increased antagonistic occasions included anemia (7%) and a pneumonitis fee of two.5%. To place this into context, Rybrevant is authorized for EGFR exon 20 mutated NSCLC, however in comparison with Rybrevant, zipalertinib confirmed decrease charges of paronychia, edema, and infusion reactions. This may occasionally enhance affected person adherence and high quality of life, particularly in older and frail sufferers.
I imagine zipalertinib presents a handy oral therapy possibility with sturdy responses and CNS exercise, addressing an unmet want, significantly in sufferers who progress on prior therapies like Rybrevant. There may be an ongoing trial, RESILIENT-3, evaluating this agent within the first-line setting.
Sabari: I could not agree extra. EGFR exon 20 is an unusual or uncommon area, affecting about 1% of sufferers, however it is extremely vital to have extra oral therapeutics obtainable for our sufferers. I feel we’ve time for perhaps another, Dr. Jain. Let’s briefly talk about the NeoADAURA trial. Inform me why that was so practice-changing within the early-stage EGFR-mutant lung most cancers area.
Jain: The NeoADAURA trial was significantly fascinating, particularly as the sector more and more makes use of lively medicine within the neoadjuvant setting to make sufferers extra eligible for resection and to realize a deeper response. Nonetheless, I really feel its main significance was in demonstrating the feasibility of an EGFR TKI within the early area previous to resection, with over 90% of sufferers finally receiving definitive surgical resection.
The trial mainly examined a main endpoint of main pathologic response. Whereas this has not but been established as a transparent surrogate for long-term survival, and stays to be totally decided, it’s a heterogeneous endpoint, comprising each full pathologic response sufferers and people with viable tumor (10% or much less of the tumor remaining). However, what the examine does inform us is that this can be a possible possibility, particularly for downstaging sufferers with N2 illness, which is a very difficult space for surgical resectability and general outcomes.
What nonetheless must be seen is the share of nodal clearance after neoadjuvant therapy. This can assist decide the precise contribution of this neoadjuvant method — Tagrisso (Osimertinib) given earlier than surgical procedure — versus simply having three years of adjuvant Tagrisso on this area, which is already an authorized commonplace of care.
Sabari: I agree extra. I wish to thanks, Dr. Jain, for giving us your insights into the ASCO 2025 lung most cancers area. I additionally wish to thank the CURE neighborhood, in addition to our sufferers and our listeners. Dr. Jain, thanks for becoming a member of us.
Sabari: Thanks.
Transcript has been edited for readability and conciseness.
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