European Society of Medical Oncology Congress
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More people with non-small cell lung cancer (NSCNC) are likely to benefit from new drugs that target molecular alterations in tumor cells, with less need for chemotherapy, following results from multiple landmark clinical trials published for the first time in late-breaking presentations at the ESMO 2023 Congress .
Better results were achieved with combinations of new experimental drugs targeting common and rare tumor mutations than with standard treatments, and improvements were seen in both early- and late-stage non-small cell lung cancer (NSCNC), type of lung cancer responsible for approximately eight out of 10 cases of the disease.
"The results are very impressive and mean that we can expect important changes in the first-line treatment for non-small cell lung cancer (NSCNC) patients with these addressable tumor cell alterations, and in the way we care for them." patients whose previous treatment has stopped working," said Professor Alessandra Curioni Fontecedro, University of Freiburg, Switzerland. "As a result, it will be more important than ever for lung cancer to be diagnosed and treated by lung cancer specialists with access to and understanding of molecular testing and findings," she added.
Dr. Elene Mariamidze, Todua Clinic, Tbilisi, Georgia, agreed: "We are entering an era of personalized medicine in non-small cell lung cancer (NSCNC) in which we use combinations of novel and targeted agents, and It will be essential to know the full mutational load of each patient under diagnosis so that we can properly plan the most effective and least toxic approach. The future of lung cancer care lies in finding the right combination of targeted treatment or chemotherapy with immunotherapy for each patient ”.
Both Curioni-Fontecedro and Mariamidze highlighted data from studies that used a new targeted drug combination in patients with advanced or metastatic NSCLC who had an EGFR mutation, one of the most common tumor mutations. When people received the combination as first-line treatment, progression-free survival (PFS) was significantly better than with the current most effective treatment for the mutation. In people who had already progressed on this current standard of care, the new targeted drugs, combined with chemotherapy, significantly improved PFS compared with chemotherapy alone.
“We still need to see the new combination lead to better overall survival compared to the current treatment. We also need to understand more about the effects in patients with brain metastases, as it appears that one of the new EGFR-targeting agents used in these studies has good penetration into brain tissue,” Curioni-Fontecedro commented.
“These studies show that patients now have a potentially new drug combination for their treatment that works partly by targeting EGFR mutations and partly by directing immune cells to destroy cancer cells. The fact that the combination worked better than the current standard treatment, and not just better than placebo, shows tangible benefits for this new approach,” Mariamidze added.
Results from non-small cell lung cancer (NSCNC) studies presented at the ESMO 2023 Congress also suggest that the use of mutation-targeted treatment may reduce the need for chemotherapy in some patients, including those with some more tumor alterations. rare cases for which targeted treatment options have previously been limited. These include patients with operable ALK-positive early-stage NSCLC, those with advanced NSCLC with RET mutation, and those with the less common and more difficult to treat EGFR mutation, exon 20 insertion, advanced NSCLC.
Additionally, the study data reinforce the value of adding immunotherapy to chemotherapy in some types of NSCLC, including using this treatment before surgery in patients with operable cancers to shrink tumors and indicate a likely response to additional treatment afterward. of surgery (so-called neoadjuvant treatment).
“We know that patients have a better prognosis if pre-surgical lung cancer treatment leads to the disappearance of the tumor on pathology reports after surgery (pathological complete response pCR) than if obvious cancer cells are still present in the postsurgical material. . “The new results show that adding immunotherapy to chemotherapy before surgery and then continuing maintenance immunotherapy for a year after surgery is more effective than simply giving chemotherapy before surgery,” Mariamidze said.
Even for patients with advanced or metastatic non-small cell lung cancer (NSCNC) who have relapsed after previous treatments and can only receive chemotherapy, there is good news. Targeting chemotherapy more precisely to tumors using antibody-drug conjugates, namely antibodies that recognize specific proteins commonly found in lung cancers, significantly improved progression-free survival (PFS) compared to currently used chemotherapy. ).
“The approach using these antibody-drug conjugates will make a big difference for the majority of patients with advanced or metastatic NSCLC who have stopped responding to first- and second-line treatments, regardless of whether they have target mutations. We need to know more about the side effects of this approach, but these findings are likely to change the standard of care for these patients,” Curioni-Fontecedro predicted.
Following such promising data on NSCLC presented at ESMO 2023, the next step for both Curioni-Fontecedro and Mariamidze is to better understand the sequence of treatments that will provide the best outcomes for patients.
“We still face the dilemma of what to do after patients have received these promising new drugs and need additional treatment. It will be very important to understand the treatment sequence now that we have many more options for treating NSCLC so that we can achieve the best possible outcomes for each patient,” Curioni-Fontecedro said.
“Very few patients benefit from a single therapy and most will need combinations of treatments at different points in their lung cancer care. "We need more research to show when and how to attack different mutations, possibly including new targets, and to help establish the ideal treatment plan for lung cancer patients who develop extensive disease," Mariamidze concluded.
References
1 Abstract – LBA14. Cho BC et al. Amivantamab plus lazertinib vs osimertinib as first-line treatment in patients with EGFR-mutated, advanced non-small cell lung cancer (NSCLC): primary results from butterfly, a Phase 3, global, randomized, controlled trial will be presented by Byoung Chul Cho during Presidential 3 Session on Monday, 23 October, 16:30 to 18:15 (CEST) in Madrid Auditorium – Hall 6.
2 Abstract – LBA15. Passaro A et al. Amivantamab plus chemotherapy (with or without lazertinib) vs chemotherapy in EGFR-mutated advanced NSCLC after progression on osimertinib: butterfly-2, a phase 3, global, randomized, controlled trial will be presented by Antonio Passaro during Presidential 3 Session on Monday, 23 October, 16:30 to 18:15 (CEST) in Madrid Auditorium – Hall 6.
3 Abstract – LBA2. Solomon BJ et al. ALINA: efficacy and safety of adjuvant alectinib versus chemotherapy in patients with early-stage ALK+ non-small cell lung cancer (NSCLC) will be presented by Ben J. Solomon during Presidential 1 Session on Saturday, 21 October 16:30 to 18:15 (CEST) in Madrid Auditorium – Hall 6.
4. Abstract – LBA4. Loong HHF et al. Randomized phase 3 study of first-line selpercatinib versus chemotherapy and pembrolizumab in RET fusion-positive NSCLC will be presented by Herbert Ho Fung Loong during Presidential 1 Session on Saturday, 21 October, 16:30 to 18:15 (CEST) in Madrid Auditorium – Hall 6.
5. Abstract – LBA5. Girard N et al. Amivantamab plus chemotherapy vs chemotherapy as first-line treatment in EGFR exon 20 insertion-mutated advanced non-small cell lung cancer (NSCLC): primary results from papillon, a randomized phase 3 global study will be presented by Nicolas Girard during Presidential 1 Session on Saturday, 21 October, 16:30 to 18:15 (CEST) in Madrid Auditorium – Hall 6.
6. Abstract – LBA1 Cascone T et al. CHECKMATE 77T: Phase 3 study comparing neoadjuvant nivolumab (nivo) plus chemotherapy (chemo) vs neoadjuvant placebo plus chemo followed by surgery and adjuvant nivol or placebo for previously untreated, resectable stage II-IIIB NSCLC will be presented by Tina Cascone during Presidential 1 Session on Saturday, 23 October, 16:30 to 18:15 (CEST) in Madrid Auditorium – Hall 6.
7. Abstract – LBA12. Ahn MJ et al. Datopotamab deruxtecan (DATO-DXD) vs docetaxel in previously treated advanced/metastatic (ADV/MET) non-small cell lung cancer (NSCLC): results of the randomized Phase 3 study TROPION-LUNG01 will be presented by Aaron E. Lisberg during Presidential 3 Session on Monday, 23 October, 16:30 to 18:15 (CEST) in Madrid Auditorium – Hall 6.
