In a selected population comprising borderline operable high T- and low N-stage non-small cell lung cancer (NSCLC), neoadjuvant nivolumab/ipilimumab plus chemoradiotherapy (CRT) resulted in high pathological responses in the phase 2 INCREASE trial. Patients with high pathological responses showed increased tumour-specific cytotoxic T cells in the blood and tumour-draining lymph nodes.
A subgroup of non-metastatic high T- and low N-stage NSCLC patients are borderline resectable and may become resectable after induction with CRT. CRT using platinum-doublet is recommended . Neoadjuvant chemotherapy combined with immunotherapy in resectable NSCLC has demonstrated an improved pathological complete response rate (pCR) . The current INCREASE trial (EudraCT 2019–003454-83) evaluated the efficacy of pre-operative CRT combined with dual immunotherapy (nivolumab/ipilimumab) on the pCR and immunological responses in patients with borderline resectable non-metastatic NSCLC. Dr Idris Bahce (Amsterdam UMC, the Netherlands) presented the first results .
The single-arm, prospective, phase 2 INCREASE trial enrolled 30 patients with resectable and borderline resectable, T3–4/N0–2 NSCLC. At the time of data cut-off, 26 participants had completed neoadjuvant treatment and 24 had undergone surgery. On day 1, platinum-doublet concurrent CRT, ipilimumab (1 mg/kg) and nivolumab (360 mg flat dose) were administered, followed by nivolumab (360 mg flat dose) after 3 weeks. Radiotherapy consisted of 50-60 Gy in once-daily doses of 2 Gy, followed by a resection 6 weeks after the last dose of radiation. The primary endpoint was the pCR (a pre-specified pCR threshold of 60% was tested against the historical rate of 30% with CRT alone). Co-primary endpoints were safety and major pathological response (MPR), i.e. ≤10% residual viable tumour cells.
Of all operated participants, 15 (63%) reached a pCR (P<0.001 against historical rate) and 19 (79%) reached an MPR (see Figure). The radiological objective response rate in the resected patients was 12.3%, indicating that the radiological response rate underestimates the pathological response. In patients with a pCR, the number of tumour-specific cytotoxic T cells (CD39+/CD8+) in peripheral blood and tumour-draining lymph nodes were more increased after neoadjuvant therapy than in non- and partial responders. The toxicity rates were acceptable.
Based on these results, Dr Bahce concluded that “in a selected population comprising borderline operable high T- and low N-stage NSCLC, neoadjuvant nivolumab/ipilimumab plus CRTis safe, provides deep pathological responses and enhances T cell activation. This data supports the use of such strategies in patients presenting with an inoperable NSCLC.”
- Eberhardt WEE, et al. Ann Oncol. 2015;26(8):1573–1588.
- Forde PM, et al. N Engl J Med. 2022;386(21):1973–1985.
- Bahce I, et al. Ipilimumab plus nivolumab and chemoradiotherapy followed by surgery in patients with resectable and borderline resectable lung cancer: The INCREASE trial. Abstract 950O. ESMO Congress 2022, 09–13 September, Paris, France.
Figure: Tumour regression per participant, including their identified key genomic alterations, histology, smoking-, and PD-L1 status .
Black bars represent full tumour regression (pCR, n=15 participants), blue illustrates partial regression (MPR, n=4 additional participants)
Copyright ©2022 Medicom Medical Publishers
« Tumour infiltrating lymphocytes identify patients with immunogenic triple-negative breast cancer Next Article
Promising clinical activity of tepotinib plus osimertinib in NSCLC with MET amplification after progression on first-line osimertinib »
Table of Contents: ESMO 2022
Letter from the Editor
High pathological responses to neoadjuvant immune checkpoint inhibition in locally advanced dMMR colon cancer
Fruquintinib: a potential new treatment for patients with refractory mCRC
Second-line avelumab is effective in patients with MSI-H/dMMR mCRC
Upper Gastrointestinal Cancer
Deep learning models predict the risk of relapse and the mutational profile in GIST
Addition of pembrolizumab to lenvatinib does not improve OS in advanced HCC
New, highly selective inhibitor of FGFR2 driver alterations and resistance mutations
Chemo-immunotherapy in gastric cancer is more effective when administered in parallel
Tumour infiltrating lymphocytes identify patients with immunogenic triple-negative breast cancer
OS benefit of abemaciclib in HR-positive/HER2-negative advanced breast cancer not (yet) statistically significant
OS benefit of sacituzumab govitecan in pre-treated HR-positive/HER2-negative metastatic breast cancer
A pathway from air pollution to lung cancer in non-smokers identified
Selective KRASG12C inhibitor sotorasib demonstrates superior PFS and ORR compared to docetaxel in previously treated patients with NSCLC
Promising clinical activity of tepotinib plus osimertinib in NSCLC with MET amplification after progression on first-line osimertinib
High pathological responses in borderline resectable NSCLC patients after induction with dual immunotherapy and concurrent chemoradiotherapy
Treatment with tumour-infiltrating lymphocytes for advanced melanoma outperforms ipilimumab
Neoadjuvant pembrolizumab outperforms adjuvant pembrolizumab in resectable stage III–IV melanomas
Survival-benefit of neoadjuvant T-VEC maintained over 5 years of follow-up
Baseline ctDNA predicts survival in resected stage III–IV melanoma
Genitourinary Cancer – Prostate Cancer
Overall survival benefit of abiraterone in mHSPC is maintained for 7 years
Limited benefit of adding long-term ADT to post-operative radiotherapy in prostate cancer
Intensified ADT benefits biochemical progression-free survival in biochemically relapsed prostate cancer
Genitourinary Cancer – Non-Prostate Cancer
Adjuvant nivolumab plus ipilimumab does not improve survival in patients with localised RCC at high risk of relapse after nephrectomy
Triple therapy improves progression-free survival in patients with advanced RCC versus dual therapy
Adjuvant atezolizumab does not improve outcomes for patients with RCC and increased risk of recurrence
OS benefit for advanced ovarian cancer patients treated with maintenance olaparib
Maintenance tegafur-uracil does not improve survival in locally advanced cervical cancer
Head and Neck Cancer
Adding first-line pembrolizumab to CRT in locally advanced HNSCC does not significantly prolong survival or event-free survival
5-FU-free chemotherapy combination as an alternative for first-line treatment of recurrent or metastatic HNSCC
Epstein Barr virus-specific autologous cytotoxic T lymphocytes do not improve survival in nasopharyngeal carcinoma